was also reported to play an imperative role in inducing apoptosis in breast cancer
cells by upregulating Bcl-2 expression and downregulating Bax expression, which
eventually lead to the release of cytochrome c, initiating the caspase cascade
(Mohan et al. 2012).
Interestingly, another phytochemical from the class of phenolics, known as
Scutellarin, has been proven to promote apoptosis by activating the p53 pathway
(Yang et al. 2017). Scutellarin was found to suppress the anti-apoptotic protein
Bcl-2, which eventually activates the pro-apoptotic protein, p53, leading to the
upregulation of Bax protein to induce caspase-3 dependent apoptosis in human
colon cancer (Yang et al. 2017). Another such phenolic compound, gallic acid, also
reported inducing apoptosis in cancer cells via the upregulation of the p53. This, in
turn, depolarizes the mitochondrial membrane potential, facilitates the release of
caspase-activator, cytochrome c and induces an intrinsic apoptotic pathway (Yang
et al. 2018). Role of another important phytochemical, capsaicin to induce
p53-mediated apoptosis in various cancer cells have been well elucidated in previous studies (Jin et al. 2014; Clark and Lee 2016; Garufi et al. 2016; Lee and Clark
2016).
Various other phytochemicals have been reported to play an essential role in
cancer cure by targeting nuclear factor kappa B (NF-kB), to promote cancer cell
death (Kumar et al. 2016). The fact that NF-kB is highly expressed in cancer cells is
inevitable due to its function in regulating anti-apoptotic and apoptotic genes (Tse
et al. 2007; Manu and Kuttan 2008; Oh et al. 2012; Kumar et al. 2016).
Intriguingly, various phytochemicals, including alkaloids and flavonoids, are
known to induce apoptosis in cancer cells by specifically targeting NF-kB signalling pathway. For instance, known phytochemicals including xanthohumol
(Colgate et al. 2007), Magnolol (Tse et al. 2007), Morusin (Lee et al. 2008),
urosolic acid (Manu et al. 2008), Corilagin (Gambari et al. 2012) were ostensibly
demonstrated to significantly down-regulate the expression of NF-kB in various
cancer cells. The suppression of this apoptosis-inhibitor, NF-kB, eventually leads to
tumour necrotic factor-a (TNF-a)-induced apoptosis. Recent review collectively
elucidated TNF-a induced activation of NF-kB in mitochondria to stimulate programmed cell death by the release of cytochrome c to the cytoplasm, followed by
the activation of a caspase cascade (Albensi 2019).
Besides, there are also several plant-based secondary metabolites reported to
induce the extrinsic pathway of apoptosis in cancer cells. A form of flavonol can
depict this, kaempferol, which has been previously reported to up-regulate the
expression of FasL, leading to the activation of caspase-8 in colon cancer cells (Lee
et al. 2014). Bid protein, which is cleaved by the activated caspase-8 in the means
of extrinsic apoptosis pathway, is then translocated into mitochondria, promoting
intrinsic apoptosis (Lim et al. 2014). Another phytochemical known to encourage
the extrinsic pathway is a phenolic compound called hispidin. Hispidin was scientifically proven to increase the level of death receptor 3 in colon cancer cells,
leading to activation of the caspases involved in the extrinsic apoptosis pathway,
namely, caspase-1 and caspase-8, along with the cleavage of PARP to induce cell
death (Hengartner 2000).
4 The Role of Phytochemicals in Cancer Prevention and Cure
133
cells by upregulating Bcl-2 expression and downregulating Bax expression, which
eventually lead to the release of cytochrome c, initiating the caspase cascade
(Mohan et al. 2012).
Interestingly, another phytochemical from the class of phenolics, known as
Scutellarin, has been proven to promote apoptosis by activating the p53 pathway
(Yang et al. 2017). Scutellarin was found to suppress the anti-apoptotic protein
Bcl-2, which eventually activates the pro-apoptotic protein, p53, leading to the
upregulation of Bax protein to induce caspase-3 dependent apoptosis in human
colon cancer (Yang et al. 2017). Another such phenolic compound, gallic acid, also
reported inducing apoptosis in cancer cells via the upregulation of the p53. This, in
turn, depolarizes the mitochondrial membrane potential, facilitates the release of
caspase-activator, cytochrome c and induces an intrinsic apoptotic pathway (Yang
et al. 2018). Role of another important phytochemical, capsaicin to induce
p53-mediated apoptosis in various cancer cells have been well elucidated in previous studies (Jin et al. 2014; Clark and Lee 2016; Garufi et al. 2016; Lee and Clark
2016).
Various other phytochemicals have been reported to play an essential role in
cancer cure by targeting nuclear factor kappa B (NF-kB), to promote cancer cell
death (Kumar et al. 2016). The fact that NF-kB is highly expressed in cancer cells is
inevitable due to its function in regulating anti-apoptotic and apoptotic genes (Tse
et al. 2007; Manu and Kuttan 2008; Oh et al. 2012; Kumar et al. 2016).
Intriguingly, various phytochemicals, including alkaloids and flavonoids, are
known to induce apoptosis in cancer cells by specifically targeting NF-kB signalling pathway. For instance, known phytochemicals including xanthohumol
(Colgate et al. 2007), Magnolol (Tse et al. 2007), Morusin (Lee et al. 2008),
urosolic acid (Manu et al. 2008), Corilagin (Gambari et al. 2012) were ostensibly
demonstrated to significantly down-regulate the expression of NF-kB in various
cancer cells. The suppression of this apoptosis-inhibitor, NF-kB, eventually leads to
tumour necrotic factor-a (TNF-a)-induced apoptosis. Recent review collectively
elucidated TNF-a induced activation of NF-kB in mitochondria to stimulate programmed cell death by the release of cytochrome c to the cytoplasm, followed by
the activation of a caspase cascade (Albensi 2019).
Besides, there are also several plant-based secondary metabolites reported to
induce the extrinsic pathway of apoptosis in cancer cells. A form of flavonol can
depict this, kaempferol, which has been previously reported to up-regulate the
expression of FasL, leading to the activation of caspase-8 in colon cancer cells (Lee
et al. 2014). Bid protein, which is cleaved by the activated caspase-8 in the means
of extrinsic apoptosis pathway, is then translocated into mitochondria, promoting
intrinsic apoptosis (Lim et al. 2014). Another phytochemical known to encourage
the extrinsic pathway is a phenolic compound called hispidin. Hispidin was scientifically proven to increase the level of death receptor 3 in colon cancer cells,
leading to activation of the caspases involved in the extrinsic apoptosis pathway,
namely, caspase-1 and caspase-8, along with the cleavage of PARP to induce cell
death (Hengartner 2000).
4 The Role of Phytochemicals in Cancer Prevention and Cure
133