4.6 Role of Phytochemicals in Cancer Cure Via
Autophagy Induction
Autophagy, a word originated from Greek meaning self-eating, is a self-digestion
approach leading to cellular degradation of the subcellular materials such as
organelles and proteins to generate energy and metabolic precursors for prolonging
cell survival (Glick et al. 2010). The cytoplasmic proteins and cellular organelles
will be enveloped in autophagosomes and degraded by fusion with lysosomes
during this process. The cellular stress response that usually serves as a quality
control mechanism leads to apoptosis-independent cell death. Various forms of
autophagy have been described, including macroautophagy, microautophagy and
chaperone-mediated autophagy (Sharma et al. 2014). It is a morphological
description, and no decisive indication of precise mechanisms underlying
autophagy-persuaded cell death can be witnessed (Tsujimoto and Shimizu 2005).
Numerous phytochemicals, namely phenols, alkaloids, flavones and organic acids
are stated to be autophagy regulators, and it was revealed that autophagy might
exhibit either cytoprotective or cytotoxic role in natural products phytochemicals
treated cancer cells (Wang and Feng 2014).
Characteristics of cancer cells, including enhanced cell proliferation, altered
apoptotic pathways, and reprogrammed cellular metabolism, all together have
shown to influence the autophagic route (Linder and Kögel 2019). Most
chemotherapeutic drugs promote autophagy, which is generally considered a
cytoprotective response in that its inhibition frequently promotes apoptotic cell
death (Sharma et al. 2014). In some circumstances, both autophagy and apoptosis
are required in parallel pathways to contribute to cell death (Mettlin 1997). Under
stress conditions, it can induce programmed cell death, called
“autophagy-dependent cell death” (ADCD). Several reports have indicated that a
variety of naturally occurring compounds play roles in the prevention or therapy of
cancer, and their bioactive compounds lead to autophagy. Recent studies have
suggested the role of phytochemicals in modulating the autophagy pathway. The
Resveratrol, found abundantly in grape skins and red wine, induced cell death and
growth inhibition in ovarian cancer cell lines, through autophagocytosis (Kim et al.
2011). Resveratrol induced molecular features of apoptosis, including the mitochondrial release of cytochrome c and caspase activation, resveratrol-treated cells
exhibited the morphologic and ultrastructural changes indicative of autophagocytic
death (Opipari et al. 2004). Soy-derived isoflavone, genistein, was also shown to
induce both apoptosis and autophagy (Kueck et al. 2007). Genistein induced
autophagy in ovarian cancer cells, indicating recruitment and localization of LC3-II
to autophagosomes (Gossner et al. 2007).
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B. Cilwyn et al.
Autophagy Induction
Autophagy, a word originated from Greek meaning self-eating, is a self-digestion
approach leading to cellular degradation of the subcellular materials such as
organelles and proteins to generate energy and metabolic precursors for prolonging
cell survival (Glick et al. 2010). The cytoplasmic proteins and cellular organelles
will be enveloped in autophagosomes and degraded by fusion with lysosomes
during this process. The cellular stress response that usually serves as a quality
control mechanism leads to apoptosis-independent cell death. Various forms of
autophagy have been described, including macroautophagy, microautophagy and
chaperone-mediated autophagy (Sharma et al. 2014). It is a morphological
description, and no decisive indication of precise mechanisms underlying
autophagy-persuaded cell death can be witnessed (Tsujimoto and Shimizu 2005).
Numerous phytochemicals, namely phenols, alkaloids, flavones and organic acids
are stated to be autophagy regulators, and it was revealed that autophagy might
exhibit either cytoprotective or cytotoxic role in natural products phytochemicals
treated cancer cells (Wang and Feng 2014).
Characteristics of cancer cells, including enhanced cell proliferation, altered
apoptotic pathways, and reprogrammed cellular metabolism, all together have
shown to influence the autophagic route (Linder and Kögel 2019). Most
chemotherapeutic drugs promote autophagy, which is generally considered a
cytoprotective response in that its inhibition frequently promotes apoptotic cell
death (Sharma et al. 2014). In some circumstances, both autophagy and apoptosis
are required in parallel pathways to contribute to cell death (Mettlin 1997). Under
stress conditions, it can induce programmed cell death, called
“autophagy-dependent cell death” (ADCD). Several reports have indicated that a
variety of naturally occurring compounds play roles in the prevention or therapy of
cancer, and their bioactive compounds lead to autophagy. Recent studies have
suggested the role of phytochemicals in modulating the autophagy pathway. The
Resveratrol, found abundantly in grape skins and red wine, induced cell death and
growth inhibition in ovarian cancer cell lines, through autophagocytosis (Kim et al.
2011). Resveratrol induced molecular features of apoptosis, including the mitochondrial release of cytochrome c and caspase activation, resveratrol-treated cells
exhibited the morphologic and ultrastructural changes indicative of autophagocytic
death (Opipari et al. 2004). Soy-derived isoflavone, genistein, was also shown to
induce both apoptosis and autophagy (Kueck et al. 2007). Genistein induced
autophagy in ovarian cancer cells, indicating recruitment and localization of LC3-II
to autophagosomes (Gossner et al. 2007).
138
B. Cilwyn et al.