DOI:http://dx.doi.org/10.7314/APJCP.2013.14.4.

2213
Anti-Cancer Mechanisms and Nano-Suspension Formulation for the Marine Algae Product Fucoxanthin

MINI-REVIEW

Anti-Cancer Mechanism and Possibility of Nano-Suspension

Formulation for a Marine Algae Product Fucoxanthin
Srinivasan Muthuirulappan*, Steffi Pulikodan Francis
Abstract
Recently, use of natural products available from marine sources, and especially algae products, are receiving
more attention. Scientific evidence for claimed nutraceutical and therapeutical effects of one such marine algae
product, fucoxanthin, is discussed in this paper with a summary of the currently available literature regarding
its antioxidant, anti-obesity and anticancer activities. It is safe for use in humans, but as it has poor solubility
a nano-suspension mode of delivery may be adopted to improve efficacy of supplments. We conclude from
ourliterature review that the marine algae product fucoxanthin has significant antioxidant, anti-obesity and
anticancer activity with established mechanisms of action.
Keywords: Anti-cancer mechanism - antioxidant activity - anti-obesity - fucoxanthin - marine algae

Asian Pacific J Cancer Prev, 14 (4), 2213-2216

Introduction damage (Kelman et al., 2012). Marine food products

contain carotenoids (asthaxantin, lutein, beta-carotene,
The marine carotenoid fucoxanthin (FX) can be found fucoxanthin), have shown an antioxidant effect in reducing
in marine brown seaweeds, macro algae, microalgae, oxidative markers stress (Riccioni, 2012).
diatoms and has significant biological properties. FX has the ability to protect against oxidative stress
Numerous studies have shown that fucoxanthin has induced by UV-B radiation and which might be applied
considerable potential and promising applications in to antioxidant and cosmeceutical industries (Heo and
human health (Peng et al., 2011). FX is a xanthophyll Jeon, 2009; Sangeetha et al., 2009) demonstrated that
present in brown algae, it is an orange-colored pigment FX has greater potential than beta-carotene in modulating
of edible brown algae consumed in Eastern Asia suppress lipid peroxidation, catalase and glutathione transferase in
carcinogenesis and obesity in rodents (Yonekura et al., plasma and liver of retinol deficiency rats. Fucoxanthin
2010). prevents skin photoaging in UVB-irradiated hairless
FX has been attributed with extraordinary potential mice, possibly via antioxidant and antiangiogenic effects
for protecting the organism against a wide range of on topical treatment (Urikura et al., 2011). FX showed
diseases (Kim and Pangestuti, 2011). In the prevention strong antioxidant activity which is attributed to quenching
and treatment of cancer antioxidants and anti-obesity singlet oxygen and scavenging free radicals (Miyashita,
therapies play vital role. FX not only directly acts on tumor 2009).
cell but also prevents the formation of cancer cells due to FX extracts exhibited antioxidant activity in noncellular
oxidative stress and obesity. Many of the studies showed systems and in activated RAW 264.7 macrophages, as
that FX could be used as therapy for oxidative stress and well as in ex vivo assays in plasma and erythrocytes,
obesity. FX acts directly on fat tissues and promote the heat after the 4 week treatment in rats (Zaragoza et al., 2008).
production which depletes the fat deposition in adipose The antioxidant activities of FX was assessed in vitro
tissues. with respect to radical scavenging and singlet oxygen
quenching abilities and hydroxyl radical scavenging was
Antioxidant Activity assessed by the electron spin resonance (ESR) technique.
Both analyses showed the superoxide radical scavenging
Marine algae contain a wide variety of bioactive activity (Sachindra et al., 2007).
compounds; many of them have commercial applications
in pharmaceutical, medical, cosmetic, nutraceutical, food Anti-obesity Activity
and agricultural industries. Natural antioxidants, found
in many algae play an important role against various Obesity is the leading metabolic disorder with rapidly
diseases through protection of cells from oxidative growing prevalence throughout the world. As it could

Medicinal Chemistry and Nanoscience Research Laboratory, Centre for Research and Development, PRIST University, Thanjavur
- 613403, Tamilnadu, India *For correspondence: sriniclic@gmail.com
Asian Pacific Journal of Cancer Prevention, Vol 14, 2013 2213
Srinivasan Muthuirulappan and Steffi Pulikodan Francis
lead to heart failure, Liver disease and cancer, there is an FX or FXOH induced cell cycle was arrested during
urgent need to find a suitable drug for lifelong use. Recent G phase and caspase-dependent apoptosis. They also
research shows only a few molecular targets are more silenced NF-kappa B, AP-1 and Akt activation, in
successful for anti-obesity prevention and treatment. One conjunction with down-regulation of anti-apoptotic
of the keys is the action on the uncoupling proteins found proteins and cell cycle regulators and resulted the reduced
in mitochondria of abdominal white adipose tissue (WAT) growth of PEL-cell tumors. Study showed that topical
which oxidize fatty acids to produce heat (Miyashita et application of fucoxanthin (1%) significantly suppressed
al., 2011). mRNA sexpression of cyclooxygenase (COX)-2,
In this direction the use of plants and edible seaweeds endothelin receptor A, p75 neurotrophin receptor (NTR),
are better than synthetic drugs the later that cause adverse prostaglandin E receptor 1 (EP1), melanocortin 1 receptor
effects in long term treatment. Brown seaweeds contain (MC1R) and tyrosinase-related protein 1. The effect of FX
Fucoxanthin is known to reduce excess fat. Administration on skin melanogenic mRNA expression was evaluated
of fucoxanthin produced anti-obesity effects by reducing by real time reverse transcription polymerase chain
the expression of uncoupling proteins UCP1 and UCP1 reaction. FX inhibited tyrosinase activity, melanogenesis
(Okada et al., 2011). Fucoxanthin is converted to in melanoma and UVB-induced skin pigmentation
fucoxanthinol and amarouciaxanthin-A. This metabolite (Shimoda et al., 2010). Fucoxanthin-induced apoptosis
of fucoxanthin in white adipose tissue suppresses in human leukemia cell HL-60 cells triggered Bcl-xL
adipocyte differentiation and development (Yim et al., signaling pathway in HL-60 cells. Study showed that ROS
2011; Lai et al., 2012) investigated the inhibitory effects are generated during fucoxanthin-induced cytotoxicity
of fucoxanthin, on the differentiation of preadipocytes and and apoptosis in HL-60 cells. N-acetylcysteine (NAC), a
recognized as triacylglycerol-lowering agent in humans ROS scavenger, was suppressed by fucoxanthin-induced
which is also observed by (Hu et al., 2012). cytotoxicity and apoptosis. Fucoxanthin induced the
cleavage of caspases -3 and -7, and poly-ADP-ribose
Anticancer Mechanism polymerase (PARP) and a decrease of Bcl-xL levels. It
was demonstrated that FX generated ROS and that the
Carotenoids are natural fat-soluble pigments that accumulation of ROS performed a crucial role in the
provide bright coloration to plants and animals. Various fucoxanthin-induced Bcl-xL signaling pathway (Kim et
carotenoids, such as beta-carotene, a-carotene, lycopene, al., 2010).
lutein, zeaxanthin, beta-cryptoxanthin, fucoxanthin, Liu et al. (2009) hypothesized that fucoxanthin
canthaxanthin and astaxanthin, have been proven to have may cause cell cycle arrest and enhance gap junctional
anti-carcinogenic activity in several tissues. Preclinical intercellular communication (GJIC) in SK-Hep-1 human
studies have shown that some carotenoids have potent hepatoma cells. Results revealed that FX strongly inhibited
antitumor effects both in vitro and in vivo models. Since the proliferation of SK-Hep-1 cells at 24h of incubation.
chemoprevention is one of the most important strategies in In SK-Hep-1 cells, fucoxanthin caused cell cycle arrest at
the control of cancer development, molecular mechanism- G0/G1 phase and induced cell apoptosis. FX was found
based cancer chemoprevention using carotenoids seems to to be an antiproliferative against SK-Hep-1 cells and the
be an attractive approach (Tanaka et al., 2012). effect is associated with up regulation of Cx32 and Cx43,
Fucoxanthin inhibited the growth of LNCap prostate which enhances GJIC of SK-Hep-1 cells.
cancer cells in a dose-dependent manner. FX activated Satomi and Nishino (2009) suggested that gadd45a is
c-Jun N-terminal kinase (SAPK/JNK), while the inhibition closely related with the G1 arrest induced by fucoxanthin,
of SAPK/JNK attenuated the induction of G (1) arrest and and that the pattern of MAPK involvement in the induction
GADD45A expression by fucoxanthin (Satomi, 2012). of gadd45a and G1 arrest by fucoxanthin differs its
Fucoxanthin treatments was found to induce apoptosis antiproliferative effect depending on the cell type. Zhang
through caspase-3 activation in PC-3 human prostate et al. (2008) determined antigrowth and apoptosis-
cancer cells (Kotake-Nara et al., 2005). FX has strong induction activity of fucoxanthin from dietary Laminaria
antioxidant and cytotoxicity against breast cancer (MCF- japonica against EJ-1 human bladder cancers. Fucoxanthin
7) with IC50=11.5 mug/ml and concluded that FX could significantly reduced the cell viability in a dose- and time-
be used as antioxidant and as an antitumor compound dependent manner. The induction of apoptosis in EJ-1 cells
(Ayyad et al., 2011). Human gastric adenocarcinoma was characterized by morphological changes, DNA ladder,
MGC-803 cells when treated with FX, fucoxanthin (50 and increased percentage of hypodiploid cells, activating
or 75 muM) increased the ratio of cell in G2/M phase caspase-3 activity.
and apoptotic MGC-803 cells on a dose-dependent Ishikawa et al. (2008) evaluated the anti- Adult T-cell
manner (Yu et al., 2011). When a human prostate cancer leukemia (ATL) effects of fucoxanthin and its metabolite,
cells, PC-3, DU 145 and LNCap, were evaluated with fucoxanthinol. Both carotenoids inhibited cell viability
carotenoid-supplemented medium for 72 h at 20 micro of HTLV-1-infected T-cell lines and ATL cells, and
mol/L, 5,6-monoepoxy carotenoids. Results suggested fucoxanthinol was approximately twice more potent
that fucoxanthin have the potential to reduce the risk of than fucoxanthin. Both carotenoids induced cell cycle
prostate cancer (Kotake-Nara et al., 2001). arrest during G(1) phase by reducing the expression of
Yamamoto et al. (2011) evaluated the anti-Primary cyclin D1, cyclin D2, CDK4 and CDK6, and inducing
effusion lymphoma (PEL) with FX and its metabolite, the expression of GADD45 alpha, and induced apoptosis
fucoxanthinol (FXOH). Treatment of PEL cells with by reducing the expression of Bcl-2, XIAP, cIAP2 and
2214 Asian Pacific Journal of Cancer Prevention, Vol 14, 2013
 DOI:http://dx.doi.org/10.7314/APJCP.2013.14.4.2213
Anti-Cancer Mechanisms and Nano-Suspension Formulation for the Marine Algae Product Fucoxanthin
survivin. The induced apoptosis was associated with Ishikawa C, Tafuku S, Kadekaru T (2008). Anti-adult T-cell
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