Targeting Cancer with Phytochemicals via Their Fine Tuning of the Cell Survival Signaling Pathways

Abstract

The role of phytochemicals as potential prodrugs or therapeutic substances against tumors has come in the spotlight in the very recent years, thanks to the huge mass of encouraging and promising results of the in vitro activity of many phenolic compounds from plant raw extracts against many cancer cell lines. Little but important evidence can be retrieved from the clinical and nutritional scientific literature, where flavonoids are investigated as major pro-apoptotic and anti-metastatic compounds. However, the actual role of these compounds in cancer is still far to be fully elucidated. Many of these phytochemicals act in a pleiotropic and poorly specific manner, but, more importantly, they are able to tune the reactive oxygen species (ROS) signaling to activate a survival or a pro-autophagic and pro-apoptosis mechanism, depending on the oxidative stress-responsive endowment of the targeted cell. This review will try to focus on this issue.

Flavonoids as Anticancer Agents

“…The ability of flavonoids to scavenge free radicals, regulate cellular metabolism, and prevent oxidative stress-related diseases have been demonstrated in numerous studies [18][19][20][21]36,37]. There is accumulating evidence that many flavonoids exert anticancer activity, however, the molecular mechanisms responsible for this effect have not been fully elucidated yet.…”

“…Flavonoids exert a wide variety of anticancer effects: they modulate ROS-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness [18][19][20][21]36,37].…”

“…Flavonoids are potent antioxidants [11] protecting plants from unfavorable environmental conditions [1], therefore they have attracted attention and have been used in numerous epidemiological and experimental studies to assess their possible beneficial effects in multiple acute and chronic human disorders [18]. In vitro and in vivo studies have shown that flavonoids could exert anti-inflammatory, immunomodulatory [19] and strong anticancer activities [18,20,21].…”

Arsenic intoxication: general aspects and chelating agents

“…Medicinal plants currently attract the scientific interest as potential remedies in case of toxic metal poisoning due to their lesser adverse effects (Mehrandish et al 2019), since their health benefits for humans are caused by the totality of secondary metabolites, including important antioxidant molecules flavonoids, accompanied by various macroelements and trace elements (Konieczynski et al 2018) (Table 1). Flavonoids possess a number of properties ranging from in vitro antioxidant and anti-inflammatory effects, ROS scavengers activity, to chelation ability for metal ions (Cherrak et al 2016;Chirumbolo et al 2018;Fang et al 2002;Korkina and Afanas'ev 1997). These polyphenols induce phase II detoxifying enzymes (e.g., glutathione S-transferase) and CYP (Cytochromes P450)-mediated detoxification, which is of significant impact on the inactivation of toxicants (Chirumbolo et al 2018;Valko et al 2006).…”

“…Flavonoids possess a number of properties ranging from in vitro antioxidant and anti-inflammatory effects, ROS scavengers activity, to chelation ability for metal ions (Cherrak et al 2016;Chirumbolo et al 2018;Fang et al 2002;Korkina and Afanas'ev 1997). These polyphenols induce phase II detoxifying enzymes (e.g., glutathione S-transferase) and CYP (Cytochromes P450)-mediated detoxification, which is of significant impact on the inactivation of toxicants (Chirumbolo et al 2018;Valko et al 2006). A report on As-induced toxicity in Swiss albino mice treated with naringenin showed significant amelioration in the hematological and serum biochemical profiles and normalization of the hepatic and renal functions (Mershiba et al 2013;Roy et al 2014).…”