Numerous studies have established a plausible link between carotenoids and its effect in therapy and prevention of cancers [1-7]. Several meta-analysis studies have
further verified the role played by the carotenoids in cancer pathogenesis [8-13]. The carotenoids having anti-cancerous activity includes α and β carotenes, lycopene,
lutein, zeaxanthin, fucoxanthin, canthaxanthine and astaxanthine etc [7]. The anti-cancerous activity is primarily attributed to their anti-oxidant
activity [14,15],however a few of them modulate signaling pathways involved in apoptosis, cell proliferation, and autophagy [1-7]. Some of these carotenoids with their anti-cancerous
activity are described below.
α and β carotenes: A number of studies have demonstrated that the α and β carotenes posses strong antioxidant activities and thus posses anti-cancerous activity
[16]. However α carotenes are believed to posses’ higher antioxidant activity compared to β carotenes and thus is considered to be more protective [17]. However significant
anti-tumor activity has been described for β carotenes [18] . A number of mechanisms has been suggested for this anti-cancerous activity including induction of connexins
(Connexin 43 in this case) and thus limiting proliferation of cells [19,20] or through modulating redox signaling mechanisms [21].
Lycopene: Lycopene has been described to protect and prevent from a variety of cancers including colon cancer[22,23],
prostate cancer [22,23], lung cancer[24,25],mammary tumors [26,27], cancers of
urinary bladders [28,29],ovarian cancers [30] and hepatocarcinoma [31,32]. The anti-cancerous activity of Lycopene has
been attributed to modulation of cellular signaling besides its antioxidant activities[33,35]. Lycopene has been demonstrated to be responsible for dissociation of
Antioxidant Response Element regulatory transcription factor Nrf1 from Keap1. This dissociation result in nuclear localization of Nrf1 and induction of downstream
antioxidant cellular defense system consisting of cytoprotective enzymes such as, superoxide dismutase, heme oxygenase-1, glutamate cysteine ligase, catalase, and
thioredoxin etc [36,37]. Lycopene is also known to inhibit cell proliferation and induce apoptosis in cancerous
cells [38-40]. Lycopene induce both intrinsic [41] and extrinsic pathways of apoptosis [42]. Lycopene also leads to
cell cycle arrest through down-regulation of cyclin D1, pAKT and pBad [43].
Lutein: Although lutein has been associated with the chemoprevention of cancer [44] however its role in specific cancers remains to be established. Only
marginally significant correlation with reduction of risk of lung cancer [45] or mammary tumors [46] has been demonstrated with the lutein. However Lutein is known
to posses’ strong antioxidant activity and thus could play protective role as a chemo-preventive agent against cancers [47].
Fucoxanthin: A number of studies have suggested that fucoxanthin possess anti-cancerous activity [48-50][48-50]. The evidence for its anti-cancerous activity has
arisen from cancer lines originating from liver [51], prostate [52], colon [53], and human breast [48]. Fucoxanthin exploits multiple pathways for exerting this
anti-cancerous activity [7][54]. It can modulate a number of signaling pathways leading to cell cycle arrest [48,55,56],[48,55,56], induction of apoptosis [48], induction of
excessive autophagy [57]. Fucoxanthin down regulates expressions of Cyclins and survivin3, in a JAK/STAT dependent pathway for inducing cell cycle arrest in G2/M
phase [58]. Besides Cyclins survivin, fucoxanthin also leads to decreased levels of master regulator retinoblastoma protein and cyclin-dependent kinase 4, and
Bcl-xL and upregulates p15 and p27 that results in increased apoptosis[59] . Fucoxanthin also leads to inhibition of function of mTOR for upregulating autophagy[57].
Canthaxanthine: Similar to fucoxanthin canthaxanthine has also been demonstrated to have anti-cancerous activity in a number of cell lines and in animal
models [60-64], however its significance in the human cancers remains to be established. The anti-cancerous activity of canthaxanthine is attributed to its strong
anti-oxidant activity [65,66],but other signaling pathways are also attributed. Canthaxanthine is also known to induce
apoptosis in cancerous cell lines [63].Canthaxanthine is also known to increase gap-junctional communication (GJC) by induction of connexin43 (Cx43) gene expression and thus inhibit the cellular
proliferation [67]. Canthaxanthine has also been shown to inhibit transformation of neoplastic transformation of murine fibroblast cells [68].
Astaxanthine: Evidence of role of astaxanthine in preventing cancers in humans is lacking however various studies performed in cell lines and animal models has
suggested that the astaxanthine could play a preventive role against cancers [69-71]. Astaxanthine is known to inhibit cell proliferation and induce apoptosis and both
could be used the potent anti-cancerous activities [72]. Furthermore, Astaxanthine leads to inactivation of Erk/MAPK and PI3K/Akt that result in down regulation of NF-κB
and Wnt/β-catenin mediated signaling pathways and thus induction of apoptosis [73]. Furthermore, astaxanthine leads to down regulation of COX2 and thus indirectly activates
apoptosis [74].
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