425
2009). Carotenoids have been reported to mediate the function of PPARγ such as
growth and apoptosis of cancer cells (Zhao et al. 2016). Hence, several reports have
shown the carotenoids serve as a strong growth-inhibitory compounds in many
tumour cell including colon, leukemia, breast, prostate, melanoma and lung cells
(Gallicchio et al. 2008; Nishino et al. 2009). Some of the anticancer mechanism of
carotenoid shows that it is involved in the PPARγ-signalling pathway. Carotenoids
such as lycopene, phytofluene, β-carotene and phytoene instigate the transactivation
of PPREs in MCF7 cell cotransfected with PPARγ. This effect was less compared
to the activity of synthetic and knonw PPAR ligands like ciglitazone and 15d-PGJ 2
(Sharoni et al. 2004). Also, 3.8 μM fucoxanthin, which is a carotenoid isolated from
edible seaweed (Undaria pinnatifida) combined with 10 μM troglitaone (a synthetic
PPARγ agonist) resulted into an extensive induction of DNA fragmentation followed by reduced viability of human Caco2 colon cancer cells. However, individual
treatment with troglitazone and fucoxanthin did not show a significant effect on the
viability of Caco2 cells. In another study, 10–25 μM of lycopene exhibited no
effects on the proliferation of PC3 prostate cancer cells. But, antiproliferative effect
of PPARγ agonist like pioglitazone, ciglitazone and 15d-PGJ 2 was supported by
25 μM of lycopene, it also inhibited the expression of survival and growth- associated
genes in PC3 cancer cells and controlled the apoptosis induction by PPARγ (Rafi
et al. 2013). The proliferation of PC3 cancer cells by lutein was similar to that of
lycopene. A mild decreased proliferation was induced by lutein, it also stimulated
PPARγ agonist induced cell cycle apoptosis and arrest, changes the expression of
apoptosis and growth-associated biological marker genes (Rafi et al. 2015). The
expression of PPARγ in breast MCF7 cancer was stimulated by β-carotene (Zhao
et al. 2016). The function of β-carotene in growth inhibition and apoptosis can be
attenuated by an irreversible antagonist of PPARγ called GW9662. Consistently,
β-carotene stimulated the production of reactive oxygen species and liberation of
cytochrome C. This mechanism indicated that the expression of PPARγ and production of reactive oxygen species may be responsible for the anti-cancer activities of
β-carotene (Cui et al. 2007). In another study, carotenoids down-regulated cyclin D1
expression and upregulated cyclin-dependent kinase inhibitor p21 and PPARγ
expression (Zhang et al. 2011). Additionally, the inhibitory effects of carotenoids on
K562-cell proliferation is supported by rosiglitazone. GW9662, a specific PPARγ
inhibitor and PPARγ small interfering RNA (siRNA) activities are greatly suppressed by combination rosiglitazone and carotenoid. The activities of rosiglitazone
and carotenoids on PPARγ siRNA and GW9662 remarkably ameliorates cyclin D1
down regulation and p21 up regulation (Zhao et al. 2014). The above data indicated
that PPARγ signalling cascade is involved in the reduction of tumour cell apoptosis
by carotenoids. But, it still remain unclear whether they can act as agonist of PPARγ
and hence can stop the growth of cancer cells. The data investigated using PPARγ
CALUX reporter cell line indicated that the γ-carotene, violaxanthin, neurosporene,
lycopene, δ-carotene, phytofluene, β-carotene from tomato extracts stimulated
expression of luciferase via PPARγ2 (Gijsbers et al. 2013). Thus, carotenoids appear
to possess some PPARγ stimulating potentials (Zhao et al. 2016).
20 Carotenoids as Functional Bioactive Compounds
2009). Carotenoids have been reported to mediate the function of PPARγ such as
growth and apoptosis of cancer cells (Zhao et al. 2016). Hence, several reports have
shown the carotenoids serve as a strong growth-inhibitory compounds in many
tumour cell including colon, leukemia, breast, prostate, melanoma and lung cells
(Gallicchio et al. 2008; Nishino et al. 2009). Some of the anticancer mechanism of
carotenoid shows that it is involved in the PPARγ-signalling pathway. Carotenoids
such as lycopene, phytofluene, β-carotene and phytoene instigate the transactivation
of PPREs in MCF7 cell cotransfected with PPARγ. This effect was less compared
to the activity of synthetic and knonw PPAR ligands like ciglitazone and 15d-PGJ 2
(Sharoni et al. 2004). Also, 3.8 μM fucoxanthin, which is a carotenoid isolated from
edible seaweed (Undaria pinnatifida) combined with 10 μM troglitaone (a synthetic
PPARγ agonist) resulted into an extensive induction of DNA fragmentation followed by reduced viability of human Caco2 colon cancer cells. However, individual
treatment with troglitazone and fucoxanthin did not show a significant effect on the
viability of Caco2 cells. In another study, 10–25 μM of lycopene exhibited no
effects on the proliferation of PC3 prostate cancer cells. But, antiproliferative effect
of PPARγ agonist like pioglitazone, ciglitazone and 15d-PGJ 2 was supported by
25 μM of lycopene, it also inhibited the expression of survival and growth- associated
genes in PC3 cancer cells and controlled the apoptosis induction by PPARγ (Rafi
et al. 2013). The proliferation of PC3 cancer cells by lutein was similar to that of
lycopene. A mild decreased proliferation was induced by lutein, it also stimulated
PPARγ agonist induced cell cycle apoptosis and arrest, changes the expression of
apoptosis and growth-associated biological marker genes (Rafi et al. 2015). The
expression of PPARγ in breast MCF7 cancer was stimulated by β-carotene (Zhao
et al. 2016). The function of β-carotene in growth inhibition and apoptosis can be
attenuated by an irreversible antagonist of PPARγ called GW9662. Consistently,
β-carotene stimulated the production of reactive oxygen species and liberation of
cytochrome C. This mechanism indicated that the expression of PPARγ and production of reactive oxygen species may be responsible for the anti-cancer activities of
β-carotene (Cui et al. 2007). In another study, carotenoids down-regulated cyclin D1
expression and upregulated cyclin-dependent kinase inhibitor p21 and PPARγ
expression (Zhang et al. 2011). Additionally, the inhibitory effects of carotenoids on
K562-cell proliferation is supported by rosiglitazone. GW9662, a specific PPARγ
inhibitor and PPARγ small interfering RNA (siRNA) activities are greatly suppressed by combination rosiglitazone and carotenoid. The activities of rosiglitazone
and carotenoids on PPARγ siRNA and GW9662 remarkably ameliorates cyclin D1
down regulation and p21 up regulation (Zhao et al. 2014). The above data indicated
that PPARγ signalling cascade is involved in the reduction of tumour cell apoptosis
by carotenoids. But, it still remain unclear whether they can act as agonist of PPARγ
and hence can stop the growth of cancer cells. The data investigated using PPARγ
CALUX reporter cell line indicated that the γ-carotene, violaxanthin, neurosporene,
lycopene, δ-carotene, phytofluene, β-carotene from tomato extracts stimulated
expression of luciferase via PPARγ2 (Gijsbers et al. 2013). Thus, carotenoids appear
to possess some PPARγ stimulating potentials (Zhao et al. 2016).
20 Carotenoids as Functional Bioactive Compounds