Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer

Abstract

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic interventions in various diseases, including cancers. According to the framework of autophagy, the suppression or induction of autophagy can exert therapeutic properties through the promotion of cell death or cell survival, which are the two main events targeted by cancer therapies. Remarkably, natural products have attracted attention in the anticancer drug discovery field, because they are biologically friendly and have potential therapeutic effects. In this review, we summarize the up-to-date knowledge regarding natural products that can modulate autophagy in various cancers. These findings will provide a new position to exploit more natural compounds as potential novel anticancer drugs and will lead to a better understanding of molecular pathways by targeting the various autophagy stages of upcoming cancer therapeutics.

Nelfinavir Induces Cytotoxicity towards High-Grade Serous Ovarian Cancer Cells, Involving Induction of the Unfolded Protein Response, Modulation of Protein Synthesis, DNA Damage, Lysosomal Impairment, and Potentiation of Toxicity Caused by Proteasome Inhibition

“…Multiple studies have reported the activation of autophagy in cancer cells in response to NFV treatment [ 12 , 41 ]. Autophagy is an evolutionarily conserved biological mechanism aimed at disintegrating cellular organelles and bulky misfolded proteins, and recycling macromolecules to compensate for energy and nutrient deprivation [ 42 , 43 ]. Furthermore, the PERK-eIF2α arm of ER stress has been associated with the modulation of autophagy [ 33 ].…”

Nelfinavir induces cytotoxicity towards high-grade serous ovarian cancer cells, involving induction of the unfolded protein response, modulation of protein synthesis, DNA damage, lysosomal impairment, and potentiation of toxicity caused by proteasome inhibition

“…Multiple studies have reported activation of autophagy in cancer cells in response to NFV treatment [12, 41]. Autophagy is an evolutionarily conserved biological mechanism aimed at disintegrating cellular organelles and bulky misfolded proteins, and recycling macromolecules to compensate for energy and nutrient deprivation [42, 43]. Furthermore, the PERK-eIF2α arm of ER stress has been associated with the modulation of autophagy [33].…”

Green Tea Epigallocatechin-3-Gallate Regulates Autophagy in Male and Female Reproductive Cancer

“…Autophagy inhibitors had also been reported to sensitize immune response in therapy, as well as influence tumor stroma and normal cell function ( Gewirtz, 2016 ; Noguchi et al, 2020 ). Hence, natural product as autophagy modulator has been proposed, owing to their safe profiles whilst showing high effectiveness to diminish tumor cells ( Zhang Q. Y. et al, 2018 ; Rahman et al, 2020 ; Al-Bari et al, 2021 ). Natural product to regulate autophagy is also a novel therapeutic approach in improving fertility ( Zhu et al, 2019 ; Park et al, 2021 ).…”

“…Natural products such as cancer therapies attract growing attention due to their high effectiveness to diminish tumor cells and low toxicity to normal cells ( Zhang Q. Y. et al, 2018 ). Their autophagy roles have been put forward ( Rahman et al, 2020 ; Al-Bari et al, 2021 ). We reviewed and proposed the use of green tea EGCG as an autophagy modulator in reproductive cancer studies.…”