Role of Xenobiotic in Autophagy Inflection in Cell Death and Carcinogenesis

Macro-autophagy (herein referred to as autophagy) is considered a major degradation pathway for damaged organelles, aggregate-prone proteins, and pathogens. There is substantial evidence stating that dysfunctional autophagy is the cause of the manifestation of multifarious degenerative diseases and cancer. Xenobiotics (here, the known group I carcinogens), substances considered foreign to the human body, are associated with inciting multiple stresses such as the endoplasmic reticulum (ER) stress, mitochondrial stress, and dysfunctional lysosome. Furthermore, autophagy exhibits a dichotomous role in cancer, although a detailed description of the modulation of autophagy by the known important carcinogens is provided only by a limited number of reports. The pro-tumorigenic role of carcinogen-induced autophagy/mitophagy has been explored which maintains homeostasis in cancer. On the contrary, the association of carcinogens with the induction of autophagic cell death has been reported. In addition, certain xenobiotics for protecting cells through dampening of necrosis, inflammation, and maintenance of genome integrity have been proposed. So far, only a few studies exploring the xenobiotic-associated autophagy modulation, both in vitro and in vivo, have been reported. The synergistic effect of environmental carcinogens in relation to autophagy has been explored, although quite little was discovered. Besides describing autophagy modulation by xenobiotics in the normal cells, there are reports illuminating how autophagy modulation could be utilized as an effective therapeutic approach for the impediment of carcinogenesis and to rescue cells from cytotoxicity. In addition, the application of chemopreventive compounds for autophagy modulation mitigating cellular toxicity and carcinogenesis have been described to achieve a safer and healthier human life.