cell. Although high levels of free radicals can be a high risk of cancer for a normal
cell, a high level of free radicals can also trigger apoptosis and cell death in various
types of cancer cells. Decisively, the actions of free radicals in cancer development,
inhibition and treatment is tremendously complex and extremely challenging to
research. Alteration of redox homeostasis in cancerous and healthy cells recommends that pro-oxidant based upregulation of cellular free radicals would target
specifically against cancer cells without damaging the normal healthy cells
(Wondrak 2009). Even though the antioxidant activity of various phytochemicals is
well researched and commonly applied to stop or cure cancer, multiple phytochemicals also exhibit the pro-oxidant and free radicals generating activities under
unique conditions especially in cancer cells. Accordingly, a pro-oxidant activity
reached phytochemical might attack the cancerous cells, which is already at an
extraordinary level of free radicals with high oxidative stress without affecting the
well-tolerated non-cancerous cells (González-Bártulos et al. 2015). Several phytochemicals that target the cellular redox balance produce an exercise amount of
reactive oxygen species (ROS) (Kruk et al. 2019) and eventually leads to cell death.
Moreover, the transition metal-based phytochemicals could be favourable phytochemicals for pro-oxidant therapies (Rahal et al. 2014). Once, the metal-based
phytochemicals accumulate metals, namely iron and copper, they induced the
cycling redox reactions in the cancer cells, which will lead to the productions of the
excessive amount of free radicals, mainly the extremely damaging hydroxyl radical
species via the Fenton reaction. The phytochemicals belong to the flavonoid group,
such as quercetin and kaempferol that have been reported to exhibit the pro-oxidant
activity when a transition metal is available (Halliwell 2008).
The anticancer activity of phytochemicals via pro-oxidant activity may depend
on diverse inter-dependent routes, as shown in Fig. 4.3. Firstly, the phytochemical
will be entering the cells to start the pro-oxidant anticancer activity. Secondly, the
accumulation of phytochemicals will trigger the cell to produce an excessive
amount of free radicals. Subsequently, the excessive amount of free radicals will
trigger DNA fragmentation and DNA damages via oxidative mechanisms. An
excessive amount of free radicals in the cells will react with the cellular DNA, thus
altering its structure, and disturbing the normal function of the DNA is one of the
main reasons for DNA damage induced by pro-oxidant activity of the phytochemical (Beckman and Ames 1997). Even though the DNA molecule is an intact
molecule, free radicals can act against the DNA and can cause various types of
harm, namely alteration of DNA molecule bases, single- and double-strand DNA
molecule disruptions, loss of purines in the DNA, destruction to the deoxyribose
sugar, cross-link between DNA and protein and destruction of the naturally
occurred DNA repair systems (Srinivas et al. 2019). The DNA fragmentation will
lead to the induction of cell cycle arrest. Eventually, the cell cycle arrest will lead
the cell to apoptotic cell death (Fig. 4.3). Conclusively, the various inter-dependent
processes exhibit the beneficial effects of the pro-oxidant activity of phytochemicals
that efficiently kills the cancer cells.
4 The Role of Phytochemicals in Cancer Prevention and Cure
131
cell, a high level of free radicals can also trigger apoptosis and cell death in various
types of cancer cells. Decisively, the actions of free radicals in cancer development,
inhibition and treatment is tremendously complex and extremely challenging to
research. Alteration of redox homeostasis in cancerous and healthy cells recommends that pro-oxidant based upregulation of cellular free radicals would target
specifically against cancer cells without damaging the normal healthy cells
(Wondrak 2009). Even though the antioxidant activity of various phytochemicals is
well researched and commonly applied to stop or cure cancer, multiple phytochemicals also exhibit the pro-oxidant and free radicals generating activities under
unique conditions especially in cancer cells. Accordingly, a pro-oxidant activity
reached phytochemical might attack the cancerous cells, which is already at an
extraordinary level of free radicals with high oxidative stress without affecting the
well-tolerated non-cancerous cells (González-Bártulos et al. 2015). Several phytochemicals that target the cellular redox balance produce an exercise amount of
reactive oxygen species (ROS) (Kruk et al. 2019) and eventually leads to cell death.
Moreover, the transition metal-based phytochemicals could be favourable phytochemicals for pro-oxidant therapies (Rahal et al. 2014). Once, the metal-based
phytochemicals accumulate metals, namely iron and copper, they induced the
cycling redox reactions in the cancer cells, which will lead to the productions of the
excessive amount of free radicals, mainly the extremely damaging hydroxyl radical
species via the Fenton reaction. The phytochemicals belong to the flavonoid group,
such as quercetin and kaempferol that have been reported to exhibit the pro-oxidant
activity when a transition metal is available (Halliwell 2008).
The anticancer activity of phytochemicals via pro-oxidant activity may depend
on diverse inter-dependent routes, as shown in Fig. 4.3. Firstly, the phytochemical
will be entering the cells to start the pro-oxidant anticancer activity. Secondly, the
accumulation of phytochemicals will trigger the cell to produce an excessive
amount of free radicals. Subsequently, the excessive amount of free radicals will
trigger DNA fragmentation and DNA damages via oxidative mechanisms. An
excessive amount of free radicals in the cells will react with the cellular DNA, thus
altering its structure, and disturbing the normal function of the DNA is one of the
main reasons for DNA damage induced by pro-oxidant activity of the phytochemical (Beckman and Ames 1997). Even though the DNA molecule is an intact
molecule, free radicals can act against the DNA and can cause various types of
harm, namely alteration of DNA molecule bases, single- and double-strand DNA
molecule disruptions, loss of purines in the DNA, destruction to the deoxyribose
sugar, cross-link between DNA and protein and destruction of the naturally
occurred DNA repair systems (Srinivas et al. 2019). The DNA fragmentation will
lead to the induction of cell cycle arrest. Eventually, the cell cycle arrest will lead
the cell to apoptotic cell death (Fig. 4.3). Conclusively, the various inter-dependent
processes exhibit the beneficial effects of the pro-oxidant activity of phytochemicals
that efficiently kills the cancer cells.
4 The Role of Phytochemicals in Cancer Prevention and Cure
131