Journal of Biochemical and Molecular Toxicology, Apr 1, 2022
Cadmium and lead are widespread, nonbiodegradable heavy metals of perpetual environmental concern... more Cadmium and lead are widespread, nonbiodegradable heavy metals of perpetual environmental concerns. The present study aimed to evaluate whether sub-chronic exposure to cadmium chloride (CdCl2 ) and lead acetate [Pb(CH3 COO)2 ] induces reproductive toxicity and development of testicular germ cell neoplasia in situ (GCNIS) in swiss albino mice. The effects of resveratrol to reverse the metal-induced toxicity were also analyzed. The mice were randomly divided into four groups for metal treatments and two groups received two different doses of each metal, CdCl2 (0.25 and 0.5 mg/kg) and Pb(CH3 COO)2 (3 and 6 mg/kg). The fourth group received oral doses of 20 mg/kg resveratrol in combination with 0.5 mg/kg CdCl2 or 6 mg/kg Pb(CH3 COO)2 for 16 weeks. Toxic effects of both metals were estimated qualitatively and quantitatively by the alterations in sperm parameters, oxidative stress markers, testicular histology, and protein expressions of the treated mice. Pronounced perturbation of sperm parameters, cellular redox balance were observed with severe distortion of testicular histo-architecture in metal exposed mice. Significant overexpression of Akt cascade and testicular GCNIS marker proteins were recorded in tissues treated with CdCl2 . Notable improvements were observed in all the evaluated parameters of resveratrol cotreated mice groups. Taken together, the findings of this study showed that long-term exposure to Cd and Pb compounds, induced acute reproductive toxicity and initiation of GCNIS development in mice. Conversely, resveratrol consumption abrogated metal-induced perturbation of spermatogenesis, testicular morphology, and the upregulation of Akt cascade proteins along with GCNIS markers, which could have induced the development of testicular cancer.
Journal of Environmental Pathology Toxicology and Oncology, 2014
Mahua flower extract may provide protective effects against hepatotoxicity. The effect of Mahua f... more Mahua flower extract may provide protective effects against hepatotoxicity. The effect of Mahua flower extract (ME) was investigated on Hep G2 cell line and carbon tetrachloride (CCl 4)-induced liver damages in Swiss albino mice. To investigate its cytotoxic effect in liver cancer, Hep G2 cells were treated with different doses of ME, and cell proliferation as well as colony formation assays demonstrated dose-dependent cytotoxicity of ME towards Hep G2 cells in tissue culture. Further gene expression studies showed significant down-regulation of AKT1/2/3, p-AKT, and COX-2 proteins including up-regulation of active caspase-3 in ME treated Hep G2 cells. In in vivo experiments, the mice were pretreated with ME for 15 days. On the 16th day CCl 4 was injected intraperitoneally and after 24 h all mice were sacrificed. The antioxidant enzyme activities were measured in liver homogenates. CCl 4-induced hepatotoxicity was evidenced by significant increase in lipid peroxidation and decrease in activities of antioxidant enzymes such as GST, GSH, SOD, CAT, and GPx. Histological studies showed CCl 4-induced centrilobular necrosis and formation of fatty vacuoles in cirrhotic mice liver. Treatment with ME at a dose of 2 mg and 4 mg/kg exhibited the potential to prevent significant liver toxicity. The expression of active caspase-3 protein was down-regulated in ME treated groups compared to CCl 4 exposed animals. This study demonstrated ME mediated antioxidant activity and hepatoprotective effects; therefore it could be used in the future for treating hepatic disorders including liver cancer, especially in combination with chemotherapeutics.
Journal of Environmental Pathology Toxicology and Oncology, 2018
Cancer is a disease resulting from the deregulation of cell growth control, caused by an interact... more Cancer is a disease resulting from the deregulation of cell growth control, caused by an interaction between dietary, genetic, and environmental risk factors. Melanoma accounts for about 4% of cancers diagnosed; however they represent 75% of skin cancer-related deaths, with the incidence and death rates having increased globally over the past few decades. Spondias cytherea is a plant from the family Anacardiaceae. Its usage in the treatment of wounds, sores, and burns is reported from several countries, but the anticancer effects of the fruit have not yet been studied. We thus set out to evaluate the effects of S. cytherea fruit extract (SpE) on the epithelial to mesenchymal transition in the mouse melanoma model. B16-F10 cells cultured in varying concentrations of SpE showed a dose-dependent reduction in the ability to form colonies, which then migrate to fill up the wounded area. SpE downregulated the expression of AKT/nuclear factor kappa B/cyclooxygenase-2 (Akt/NF-κB/COX-2) responsible for cell proliferation, and reduced CD133 expression. This led to in vivo tumor shrinkage at the dose of 450 mg/kg body weight (bw). Low-level expression of vimentin on mesenchymal cells and increased E-cadherin expression on epithelial cells were observed in treated cells. The number of vasculogenic mimicry tubes that formed also decreased significantly at 450 mg/kg bw. These results suggest that S. cytherea fruit can become a useful source for chemotherapeutic drugs in the future.
Clinical Epidemiology and Global Health, Mar 1, 2018
Background: The frequency of colorectal carcinoma is inadequate in India compared to the western ... more Background: The frequency of colorectal carcinoma is inadequate in India compared to the western world. The carcinoma of colon and rectum is usually disturbing among the individuals of older age group whereas it is less frequent in younger age group. This study was based on age, gender, site of primary tumor and histopathological type of colorectal cancer cases. Methods: A retrospective study of 420 colorectal carcinoma cases admitted to Chittaranjan National Cancer Institute hospital, Kolkata, India during 2012-2016 was carried out. All the clinicopathological data was collected from the medical records of the patients. The detailed information was entered into tabular sheet and statistical analysis was performed. Results: During these five years out of total cases in the Department of Surgical Oncology, 5.09% patients with colorectal carcinoma were admitted for colectomy or hemicolectomy. The percentage of younger age group (40 year) with colorectal cancer was rise up sharply in context of older age group (>60 year). The ratio of male and female affected in colorectal cancer was 1.6:1. Rectum was the most common site 46.2% among the total cancer lesions. From histopathological data, mucinous adenocarcinoma cases were identified with (23.6%) high frequency and mostly detected at younger age group (65.7%). It was found that 18.8% patients with synchronous liver metastasis and 16.7% of patients with Type 2 diabetes mellitus were likely to develop colorectal cancer. Conclusion: The concise overview has documented an increased incidence of colorectal carcinoma patients amongst younger individuals with more aggressive forms like mucinous adenocarcinoma and also development of synchronous liver metastasis.
Aims: The cytotoxic response of an intermediate metabolite glyoxylate (Glx) on colon carcinoma ha... more Aims: The cytotoxic response of an intermediate metabolite glyoxylate (Glx) on colon carcinoma has been evaluated in vitro. Main Methods: The anti-proliferative effect of Glx was assessed on HT-29 and HCT-116 cells by performing MTT assay as well as beta-hexosaminidase assay. Evaluation of apoptotic event of Glx treated cells was measured by flow cytometry using annexin-V/PI staining. The mitochondrial membrane potential and level of ROS were estimated using DiOC 6 (3)/CCCP and DCFH-DA method, respectively. The assessment of catalase, LDH and IDH were performed.
We have identified a natural compound that activates apoptosis of epithelial cancer cells through... more We have identified a natural compound that activates apoptosis of epithelial cancer cells through activation of tumor necrosis factor-A (TNF-A), TNF receptor (TNFR)associated death domain (TRADD), and caspases. The molecule 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde (HDNC, marmelin) was isolated and characterized from ethyl acetate fraction of extracts of Aegle marmelos. HDNC treatment inhibited the growth of HCT-116 colon cancer tumor xenografts in vivo. Immunostaining for CD31 showed that there was a significant reduction in microvessels in the HDNC-treated animals, coupled with decreased cyclooxygenase-2, interleukin-8, and vascular endothelial growth factor mRNA. Using hexoseaminidase assay, we determined that HDNC inhibits proliferation of HCT-116 colon and HEp-2 alveolar epithelial carcinoma cells. Furthermore, the cancer cells showed increased levels of activated caspase-3 and induced G 1 cell cycle arrest, which was suppressed by caspase-3 inhibitors. HDNC induced TNF-A, TNFR1, and TRADD mRNA and protein expression. Moreover, caspase-8 and Bid activation, and cytochrome c release, were observed, suggesting the existence of a cross-talk between death receptor and the mitochondrial pathways. HDNC inhibited AKT and extracellular signal-regulated kinase phosphorylation both in cells in culture and in tumor xenografts. In addition, electrophoretic mobility shift assay and luciferase reporter assays showed that HDNC significantly suppressed TNF-A-mediated activation and translocation of nuclear factor-KB (NF-KB). This was further confirmed by Western blot analysis of nuclear extracts wherein levels of RelA, the p65 component of NF-KB, were significantly less in cells treated with HDNC. Together, the data suggest that the novel compound HDNC (marmelin) is a potent anticancer agent that induces apoptosis during G 1 phase of the cell cycle and could be a potential chemotherapeutic candidate.
Two new boron compoumds, dihydroxy(oxybiguanido) boron (iii) hydrochloride monohydrate (HB) and g... more Two new boron compoumds, dihydroxy(oxybiguanido) boron (iii) hydrochloride monohydrate (HB) and guanidine biboric acid adduct (GB) were used in this study to observe the antitumor effect. Leukemic blast cells isolated from chronic myeloid leukemia (CML) patients showed significant cell growth inhibition within twentyfour hours. IC50 of GB and HB was 2mg/ml. The metabolically active cells were found to be inhibited by drug treatment as assessed by MTT test. Inhibition of 3H Thymidine incorporation also supported the above result. In this study we investigated the molecular mechanisms by which HB and GB induce apoptosis in immature blast cells.
role of NO in gastric epithelial cell apoptosin during Helicobacter infi:ction remains contrnvers... more role of NO in gastric epithelial cell apoptosin during Helicobacter infi:ction remains contrnversial The aim of our study was to determine the interaction between NO and Fas mediated apoptotic signaling. Methods, Rat gastric mucosal ceils (RGM-1) were stably transfected with the pMSCV-puro vector containing the full length mouse Fas Ag eDNA. Fas Ag expressing clones were isolated and ctuaracterized, and clones expressing moderate levels of Fas Ag and moderately susceptible to Fas mediated apoptosis were chosen for this study. The apoptotic response to FasL 50ng/ml was determined in control medium, medium + lmM L-arginine (NO donor) or medium + 5raM I-NMA (N c monomethyl-L-arginine-an NO inhibitor), DNA fragmentation assay and Annex-V / propidium iodide FACS was used to qnanritate apoptosis Caspase 3 activation and PARP cleavage was detected using Western hlot, ResuhsRGM-.1 Fas Ag cells grown under standard culture conditions had a 1 6 • 0.3% level of apoptosis as detected by DNA fragmentation assay, Addition of FasL 50 n~'ml for 24 hours produced a moderate increase in apoptosis; 17.37+_2,3% When an NO donor is made avadabIe to the ceils i6 hours prior to ligand addition, protection from apoptosis is noted and the level of apoptosin decreased dramatically to 6.7 • 1.4% Conversely, when an NO inhibitor is added (L-NMA), apoptosis significantly increases to 32,24 • 3. I%. Annex-V Rl staining FACS analysis confirmed apoptosis levels, and further verified viable cells at; 98.32%, 900%, 961%, 783% in the t~specrive treatment groups. Caspase 3 and PARP cleavage was e~qdent after treatment with FasL 50 ng/m/ for 4 hours, was inhibited by pretreatment wifh L-arginine, and enhanced by L-NiVLA.. Conclusions, Gastric epithelial ceils can use L-argmme as substrate to produce NO, NO inhibits Fas mediated apoptosis at the level of caspase 3 activation, potentially via nitrosylation of caspase 3. Decreasing the availability of NO enhances Fas mediated apoptosis in gastric mucosal cells Therefore, NO may fuoction to mothdate Fas mediated apoptosls during Hdicobacter intection.
International Journal of Experimental Pathology, Feb 16, 2022
Vasculogenic mimicry (VM), an endothelial cell–independent alternative mechanism of blood supply ... more Vasculogenic mimicry (VM), an endothelial cell–independent alternative mechanism of blood supply to the malignant tumour, has long been considered as an adverse prognostic factor in many cancers. The correlation of VM with laminin‐5γ2 and the assessment of their harmonized expression as an independent risk factor have not been elucidated yet in oral squamous cell carcinoma (OSCC). CD31/PAS staining stratified 116 clinically diagnosed OSCC specimens into VM+ and VM− cohorts. The expression pattern of laminin‐5γ2 and its upstream modulator MMP2 was evaluated by immunohistochemistry and Western blot. The Kaplan–Meier and Cox regression analyses were performed to assess the survival and prognostic implications. The presence of VM demonstrated a significant correlation with the expression of laminin‐5γ2 (p < .001) and MMP2 (p < .001). This pattern was mirrored by the significant upregulation of laminin‐5γ2 and MMP2 in VM+ cohorts compared with the VM− ones. Furthermore, co‐expression of VM and laminin‐5γ2 was significantly associated with tumour grade (p = .010), primary tumour size (p < .001), lymph node metastasis (p = .001) and TNM stages (p < .001) but not with patients' age, gender, tobacco and alcohol consumption habit. Vasculogenic mimicry and laminin‐5γ2 double‐positive cohort displayed a significantly poorer disease‐free survival (DFS) and overall survival (OS). Vasculogenic mimicry, laminin‐5γ2 and their subsequent dual expression underlie a significant prognostic value for DFS [hazard ratio (HR) = 9.896, p = .028] and OS [HR = 21.401, p = .033] in OSCC patients. Together, our findings imply that VM along with laminin‐5γ2 is strongly linked to the malignant progression in OSCC and VM and laminin‐5γ2 coordination emerges as a critical prognostic biomarker for OSCC.
Asian Pacific Journal of Cancer Prevention, Feb 1, 2019
Objective: To identify high risk HPV associations by evaluating linked p16 overexpression and als... more Objective: To identify high risk HPV associations by evaluating linked p16 overexpression and also the expression of p53 and RARβ together with histopathology for risk categorization of cervical pre-neoplastic lesions. Materials and Methods: Immunohistochemical staining was performed on 100 cases of cervical pre-neoplastic lesions for expression of biomarkers like p16, p53 and RARβ for comparison with haematoxylin/eosin (HE) findings. All the experimentally generated data were statistically analyzed. Results: In this study 70% cases showed overexpression of p16INK4A increasing progressively from CIN I to CIN II but reduced in CIN III (p <0.01). p53 oncoprotein expression was seen in 51% cases, again with increments from CIN I to CIN II with slight reduction in CIN III (p<0.01). Some 24% cases showed negative immunoreactivity for the putative tumor suppressor gene RARβ (p>0.05). Conclusion: Our study provides support for the idea that p16 can be used to identify associations with HPV , as well as having potential along with p53 and RARβ for categorizing cervical pre-neoplastic cases having a higher risk of neoplastic conversion. Thus it may be concluded that accurate risk categorization can be achieved with the help of genetic markers as well as histopathology.
New Ru(ii) cyclometallated complexes have been synthesized via C(aryl)–S bond activation having p... more New Ru(ii) cyclometallated complexes have been synthesized via C(aryl)–S bond activation having potent antiproliferative activity.
One of the major causes due to cancer-related death is metastasis. The major factors contributing... more One of the major causes due to cancer-related death is metastasis. The major factors contributing to metastasis of cancer cells are epithelial-mesenchymal transition and cancer stem cells. There are multiple evidences which suggest that malfunction of epigenetic regulation in functioning of a gene is directly related to the development of cancer. The capability to change or reprogram the landscape of epigenetics in the epigenome of cancer is the most promising and guaranteed targeted therapy that leads to the reversibility of drug resistance and new modalities of treatment in cancer. This review clearly focuses on various epigenetic modifications which leads to antitumor drug resistance and how epigenetic modifiers can reverse drug resistance.
Supplementary Figure 1 from Activation of Apoptosis by 1-Hydroxy-5,7-Dimethoxy-2-Naphthalene-Carb... more Supplementary Figure 1 from Activation of Apoptosis by 1-Hydroxy-5,7-Dimethoxy-2-Naphthalene-Carboxaldehyde, a Novel Compound from Aegle marmelos
Supplementary Legends 1-4 and Materials from Activation of Apoptosis by 1-Hydroxy-5,7-Dimethoxy-2... more Supplementary Legends 1-4 and Materials from Activation of Apoptosis by 1-Hydroxy-5,7-Dimethoxy-2-Naphthalene-Carboxaldehyde, a Novel Compound from Aegle marmelos
Journal of Biochemical and Molecular Toxicology, Apr 1, 2022
Cadmium and lead are widespread, nonbiodegradable heavy metals of perpetual environmental concern... more Cadmium and lead are widespread, nonbiodegradable heavy metals of perpetual environmental concerns. The present study aimed to evaluate whether sub-chronic exposure to cadmium chloride (CdCl2 ) and lead acetate [Pb(CH3 COO)2 ] induces reproductive toxicity and development of testicular germ cell neoplasia in situ (GCNIS) in swiss albino mice. The effects of resveratrol to reverse the metal-induced toxicity were also analyzed. The mice were randomly divided into four groups for metal treatments and two groups received two different doses of each metal, CdCl2 (0.25 and 0.5 mg/kg) and Pb(CH3 COO)2 (3 and 6 mg/kg). The fourth group received oral doses of 20 mg/kg resveratrol in combination with 0.5 mg/kg CdCl2 or 6 mg/kg Pb(CH3 COO)2 for 16 weeks. Toxic effects of both metals were estimated qualitatively and quantitatively by the alterations in sperm parameters, oxidative stress markers, testicular histology, and protein expressions of the treated mice. Pronounced perturbation of sperm parameters, cellular redox balance were observed with severe distortion of testicular histo-architecture in metal exposed mice. Significant overexpression of Akt cascade and testicular GCNIS marker proteins were recorded in tissues treated with CdCl2 . Notable improvements were observed in all the evaluated parameters of resveratrol cotreated mice groups. Taken together, the findings of this study showed that long-term exposure to Cd and Pb compounds, induced acute reproductive toxicity and initiation of GCNIS development in mice. Conversely, resveratrol consumption abrogated metal-induced perturbation of spermatogenesis, testicular morphology, and the upregulation of Akt cascade proteins along with GCNIS markers, which could have induced the development of testicular cancer.
Journal of Environmental Pathology Toxicology and Oncology, 2014
Mahua flower extract may provide protective effects against hepatotoxicity. The effect of Mahua f... more Mahua flower extract may provide protective effects against hepatotoxicity. The effect of Mahua flower extract (ME) was investigated on Hep G2 cell line and carbon tetrachloride (CCl 4)-induced liver damages in Swiss albino mice. To investigate its cytotoxic effect in liver cancer, Hep G2 cells were treated with different doses of ME, and cell proliferation as well as colony formation assays demonstrated dose-dependent cytotoxicity of ME towards Hep G2 cells in tissue culture. Further gene expression studies showed significant down-regulation of AKT1/2/3, p-AKT, and COX-2 proteins including up-regulation of active caspase-3 in ME treated Hep G2 cells. In in vivo experiments, the mice were pretreated with ME for 15 days. On the 16th day CCl 4 was injected intraperitoneally and after 24 h all mice were sacrificed. The antioxidant enzyme activities were measured in liver homogenates. CCl 4-induced hepatotoxicity was evidenced by significant increase in lipid peroxidation and decrease in activities of antioxidant enzymes such as GST, GSH, SOD, CAT, and GPx. Histological studies showed CCl 4-induced centrilobular necrosis and formation of fatty vacuoles in cirrhotic mice liver. Treatment with ME at a dose of 2 mg and 4 mg/kg exhibited the potential to prevent significant liver toxicity. The expression of active caspase-3 protein was down-regulated in ME treated groups compared to CCl 4 exposed animals. This study demonstrated ME mediated antioxidant activity and hepatoprotective effects; therefore it could be used in the future for treating hepatic disorders including liver cancer, especially in combination with chemotherapeutics.
Journal of Environmental Pathology Toxicology and Oncology, 2018
Cancer is a disease resulting from the deregulation of cell growth control, caused by an interact... more Cancer is a disease resulting from the deregulation of cell growth control, caused by an interaction between dietary, genetic, and environmental risk factors. Melanoma accounts for about 4% of cancers diagnosed; however they represent 75% of skin cancer-related deaths, with the incidence and death rates having increased globally over the past few decades. Spondias cytherea is a plant from the family Anacardiaceae. Its usage in the treatment of wounds, sores, and burns is reported from several countries, but the anticancer effects of the fruit have not yet been studied. We thus set out to evaluate the effects of S. cytherea fruit extract (SpE) on the epithelial to mesenchymal transition in the mouse melanoma model. B16-F10 cells cultured in varying concentrations of SpE showed a dose-dependent reduction in the ability to form colonies, which then migrate to fill up the wounded area. SpE downregulated the expression of AKT/nuclear factor kappa B/cyclooxygenase-2 (Akt/NF-κB/COX-2) responsible for cell proliferation, and reduced CD133 expression. This led to in vivo tumor shrinkage at the dose of 450 mg/kg body weight (bw). Low-level expression of vimentin on mesenchymal cells and increased E-cadherin expression on epithelial cells were observed in treated cells. The number of vasculogenic mimicry tubes that formed also decreased significantly at 450 mg/kg bw. These results suggest that S. cytherea fruit can become a useful source for chemotherapeutic drugs in the future.
Clinical Epidemiology and Global Health, Mar 1, 2018
Background: The frequency of colorectal carcinoma is inadequate in India compared to the western ... more Background: The frequency of colorectal carcinoma is inadequate in India compared to the western world. The carcinoma of colon and rectum is usually disturbing among the individuals of older age group whereas it is less frequent in younger age group. This study was based on age, gender, site of primary tumor and histopathological type of colorectal cancer cases. Methods: A retrospective study of 420 colorectal carcinoma cases admitted to Chittaranjan National Cancer Institute hospital, Kolkata, India during 2012-2016 was carried out. All the clinicopathological data was collected from the medical records of the patients. The detailed information was entered into tabular sheet and statistical analysis was performed. Results: During these five years out of total cases in the Department of Surgical Oncology, 5.09% patients with colorectal carcinoma were admitted for colectomy or hemicolectomy. The percentage of younger age group (40 year) with colorectal cancer was rise up sharply in context of older age group (>60 year). The ratio of male and female affected in colorectal cancer was 1.6:1. Rectum was the most common site 46.2% among the total cancer lesions. From histopathological data, mucinous adenocarcinoma cases were identified with (23.6%) high frequency and mostly detected at younger age group (65.7%). It was found that 18.8% patients with synchronous liver metastasis and 16.7% of patients with Type 2 diabetes mellitus were likely to develop colorectal cancer. Conclusion: The concise overview has documented an increased incidence of colorectal carcinoma patients amongst younger individuals with more aggressive forms like mucinous adenocarcinoma and also development of synchronous liver metastasis.
Aims: The cytotoxic response of an intermediate metabolite glyoxylate (Glx) on colon carcinoma ha... more Aims: The cytotoxic response of an intermediate metabolite glyoxylate (Glx) on colon carcinoma has been evaluated in vitro. Main Methods: The anti-proliferative effect of Glx was assessed on HT-29 and HCT-116 cells by performing MTT assay as well as beta-hexosaminidase assay. Evaluation of apoptotic event of Glx treated cells was measured by flow cytometry using annexin-V/PI staining. The mitochondrial membrane potential and level of ROS were estimated using DiOC 6 (3)/CCCP and DCFH-DA method, respectively. The assessment of catalase, LDH and IDH were performed.
We have identified a natural compound that activates apoptosis of epithelial cancer cells through... more We have identified a natural compound that activates apoptosis of epithelial cancer cells through activation of tumor necrosis factor-A (TNF-A), TNF receptor (TNFR)associated death domain (TRADD), and caspases. The molecule 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde (HDNC, marmelin) was isolated and characterized from ethyl acetate fraction of extracts of Aegle marmelos. HDNC treatment inhibited the growth of HCT-116 colon cancer tumor xenografts in vivo. Immunostaining for CD31 showed that there was a significant reduction in microvessels in the HDNC-treated animals, coupled with decreased cyclooxygenase-2, interleukin-8, and vascular endothelial growth factor mRNA. Using hexoseaminidase assay, we determined that HDNC inhibits proliferation of HCT-116 colon and HEp-2 alveolar epithelial carcinoma cells. Furthermore, the cancer cells showed increased levels of activated caspase-3 and induced G 1 cell cycle arrest, which was suppressed by caspase-3 inhibitors. HDNC induced TNF-A, TNFR1, and TRADD mRNA and protein expression. Moreover, caspase-8 and Bid activation, and cytochrome c release, were observed, suggesting the existence of a cross-talk between death receptor and the mitochondrial pathways. HDNC inhibited AKT and extracellular signal-regulated kinase phosphorylation both in cells in culture and in tumor xenografts. In addition, electrophoretic mobility shift assay and luciferase reporter assays showed that HDNC significantly suppressed TNF-A-mediated activation and translocation of nuclear factor-KB (NF-KB). This was further confirmed by Western blot analysis of nuclear extracts wherein levels of RelA, the p65 component of NF-KB, were significantly less in cells treated with HDNC. Together, the data suggest that the novel compound HDNC (marmelin) is a potent anticancer agent that induces apoptosis during G 1 phase of the cell cycle and could be a potential chemotherapeutic candidate.
Two new boron compoumds, dihydroxy(oxybiguanido) boron (iii) hydrochloride monohydrate (HB) and g... more Two new boron compoumds, dihydroxy(oxybiguanido) boron (iii) hydrochloride monohydrate (HB) and guanidine biboric acid adduct (GB) were used in this study to observe the antitumor effect. Leukemic blast cells isolated from chronic myeloid leukemia (CML) patients showed significant cell growth inhibition within twentyfour hours. IC50 of GB and HB was 2mg/ml. The metabolically active cells were found to be inhibited by drug treatment as assessed by MTT test. Inhibition of 3H Thymidine incorporation also supported the above result. In this study we investigated the molecular mechanisms by which HB and GB induce apoptosis in immature blast cells.
role of NO in gastric epithelial cell apoptosin during Helicobacter infi:ction remains contrnvers... more role of NO in gastric epithelial cell apoptosin during Helicobacter infi:ction remains contrnversial The aim of our study was to determine the interaction between NO and Fas mediated apoptotic signaling. Methods, Rat gastric mucosal ceils (RGM-1) were stably transfected with the pMSCV-puro vector containing the full length mouse Fas Ag eDNA. Fas Ag expressing clones were isolated and ctuaracterized, and clones expressing moderate levels of Fas Ag and moderately susceptible to Fas mediated apoptosis were chosen for this study. The apoptotic response to FasL 50ng/ml was determined in control medium, medium + lmM L-arginine (NO donor) or medium + 5raM I-NMA (N c monomethyl-L-arginine-an NO inhibitor), DNA fragmentation assay and Annex-V / propidium iodide FACS was used to qnanritate apoptosis Caspase 3 activation and PARP cleavage was detected using Western hlot, ResuhsRGM-.1 Fas Ag cells grown under standard culture conditions had a 1 6 • 0.3% level of apoptosis as detected by DNA fragmentation assay, Addition of FasL 50 n~'ml for 24 hours produced a moderate increase in apoptosis; 17.37+_2,3% When an NO donor is made avadabIe to the ceils i6 hours prior to ligand addition, protection from apoptosis is noted and the level of apoptosin decreased dramatically to 6.7 • 1.4% Conversely, when an NO inhibitor is added (L-NMA), apoptosis significantly increases to 32,24 • 3. I%. Annex-V Rl staining FACS analysis confirmed apoptosis levels, and further verified viable cells at; 98.32%, 900%, 961%, 783% in the t~specrive treatment groups. Caspase 3 and PARP cleavage was e~qdent after treatment with FasL 50 ng/m/ for 4 hours, was inhibited by pretreatment wifh L-arginine, and enhanced by L-NiVLA.. Conclusions, Gastric epithelial ceils can use L-argmme as substrate to produce NO, NO inhibits Fas mediated apoptosis at the level of caspase 3 activation, potentially via nitrosylation of caspase 3. Decreasing the availability of NO enhances Fas mediated apoptosis in gastric mucosal cells Therefore, NO may fuoction to mothdate Fas mediated apoptosls during Hdicobacter intection.
International Journal of Experimental Pathology, Feb 16, 2022
Vasculogenic mimicry (VM), an endothelial cell–independent alternative mechanism of blood supply ... more Vasculogenic mimicry (VM), an endothelial cell–independent alternative mechanism of blood supply to the malignant tumour, has long been considered as an adverse prognostic factor in many cancers. The correlation of VM with laminin‐5γ2 and the assessment of their harmonized expression as an independent risk factor have not been elucidated yet in oral squamous cell carcinoma (OSCC). CD31/PAS staining stratified 116 clinically diagnosed OSCC specimens into VM+ and VM− cohorts. The expression pattern of laminin‐5γ2 and its upstream modulator MMP2 was evaluated by immunohistochemistry and Western blot. The Kaplan–Meier and Cox regression analyses were performed to assess the survival and prognostic implications. The presence of VM demonstrated a significant correlation with the expression of laminin‐5γ2 (p < .001) and MMP2 (p < .001). This pattern was mirrored by the significant upregulation of laminin‐5γ2 and MMP2 in VM+ cohorts compared with the VM− ones. Furthermore, co‐expression of VM and laminin‐5γ2 was significantly associated with tumour grade (p = .010), primary tumour size (p < .001), lymph node metastasis (p = .001) and TNM stages (p < .001) but not with patients' age, gender, tobacco and alcohol consumption habit. Vasculogenic mimicry and laminin‐5γ2 double‐positive cohort displayed a significantly poorer disease‐free survival (DFS) and overall survival (OS). Vasculogenic mimicry, laminin‐5γ2 and their subsequent dual expression underlie a significant prognostic value for DFS [hazard ratio (HR) = 9.896, p = .028] and OS [HR = 21.401, p = .033] in OSCC patients. Together, our findings imply that VM along with laminin‐5γ2 is strongly linked to the malignant progression in OSCC and VM and laminin‐5γ2 coordination emerges as a critical prognostic biomarker for OSCC.
Asian Pacific Journal of Cancer Prevention, Feb 1, 2019
Objective: To identify high risk HPV associations by evaluating linked p16 overexpression and als... more Objective: To identify high risk HPV associations by evaluating linked p16 overexpression and also the expression of p53 and RARβ together with histopathology for risk categorization of cervical pre-neoplastic lesions. Materials and Methods: Immunohistochemical staining was performed on 100 cases of cervical pre-neoplastic lesions for expression of biomarkers like p16, p53 and RARβ for comparison with haematoxylin/eosin (HE) findings. All the experimentally generated data were statistically analyzed. Results: In this study 70% cases showed overexpression of p16INK4A increasing progressively from CIN I to CIN II but reduced in CIN III (p <0.01). p53 oncoprotein expression was seen in 51% cases, again with increments from CIN I to CIN II with slight reduction in CIN III (p<0.01). Some 24% cases showed negative immunoreactivity for the putative tumor suppressor gene RARβ (p>0.05). Conclusion: Our study provides support for the idea that p16 can be used to identify associations with HPV , as well as having potential along with p53 and RARβ for categorizing cervical pre-neoplastic cases having a higher risk of neoplastic conversion. Thus it may be concluded that accurate risk categorization can be achieved with the help of genetic markers as well as histopathology.
New Ru(ii) cyclometallated complexes have been synthesized via C(aryl)–S bond activation having p... more New Ru(ii) cyclometallated complexes have been synthesized via C(aryl)–S bond activation having potent antiproliferative activity.
One of the major causes due to cancer-related death is metastasis. The major factors contributing... more One of the major causes due to cancer-related death is metastasis. The major factors contributing to metastasis of cancer cells are epithelial-mesenchymal transition and cancer stem cells. There are multiple evidences which suggest that malfunction of epigenetic regulation in functioning of a gene is directly related to the development of cancer. The capability to change or reprogram the landscape of epigenetics in the epigenome of cancer is the most promising and guaranteed targeted therapy that leads to the reversibility of drug resistance and new modalities of treatment in cancer. This review clearly focuses on various epigenetic modifications which leads to antitumor drug resistance and how epigenetic modifiers can reverse drug resistance.
Supplementary Figure 1 from Activation of Apoptosis by 1-Hydroxy-5,7-Dimethoxy-2-Naphthalene-Carb... more Supplementary Figure 1 from Activation of Apoptosis by 1-Hydroxy-5,7-Dimethoxy-2-Naphthalene-Carboxaldehyde, a Novel Compound from Aegle marmelos
Supplementary Legends 1-4 and Materials from Activation of Apoptosis by 1-Hydroxy-5,7-Dimethoxy-2... more Supplementary Legends 1-4 and Materials from Activation of Apoptosis by 1-Hydroxy-5,7-Dimethoxy-2-Naphthalene-Carboxaldehyde, a Novel Compound from Aegle marmelos
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