Targeting autophagy using natural compounds for cancer prevention and therapy

Abstract

Autophagy, also known as macroautophagy, is a tightly regulated process involved in the stress responses, such as starvation. It is a vacuolar, lysosomal pathway for the degradation of damaged proteins and organelles in eukaryotic cells. Autophagy also plays a key role in various tissue processes and immune responses and in the regulation of inflammation. Over the past decade, three levels of autophagy regulation have been identified in mammalian cells: 1) signaling, 2) autophagosome formation, and 3) autophagosome maturation and lysosomal degradation. Any deregulation of the autophagy processes can lead to the development of diverse chronic diseases, such as diabetes, obesity, cardiovascular disease, neurodegenerative disease, and malignancies. However, the potential role of autophagy in cancer is rather complex and has been associated with both the induction and the inhibition of neoplasia. Several synthetic autophagy modulators have been identified as promising candidates for cancer therapy. In addition, diverse phytochemicals derived from natural sources, such as curcumin, ursolic acid, resveratrol, thymoquinone, and γ‐tocotrienol, also have attracted attention as promising autophagy modulators with minimal side effects. In this review, the authors discuss the importance of autophagy regulators and various natural compounds that induce and/or inhibit autophagy in the prevention and therapy of cancer.

<p>miR-193b Increases the Chemosensitivity of Osteosarcoma Cells by Promoting FEN1-Mediated Autophagy</p>

“…34,35 Several reports have highlighted the participation of autophagy regulation in different cancers, including OS. 36,37 In the present study, we showed that miR-193b significantly increases the expression of autophagy-related proteins in OS cells and promotes cell sensitivity to epirubicin treatment, indicating that miR-193b-induced OS cell apoptosis may be autophagy-dependent.…”

Sodium butyrate inhibits migration and induces AMPK‐mTOR pathway‐dependent autophagy and ROS‐mediated apoptosis via the miR‐139‐5p/Bmi‐1 axis in human bladder cancer cells

“…Furthermore, emerging studies have demonstrated a link between autophagy and apoptosis. [39][40][41][42] Atg7, an essential autophagy regulator, plays important roles in disease development and progression. 31,33 In this study, we used ATG7 siRNA and 3-MA to inhibit autophagy and explore the potential role of autophagy in NaB-induced apoptosis.…”

“…38 However, autophagy plays a dual role in cancer development and progression and is a vital target in human disease prevention and therapy. 39 Autophagy can not only promote apoptosis or induce autophagic cell death to suppress the development of malignancy but also degrade and recycle cellular components to maintain homeostasis and promote tumor cell survival. 40 A study reported that inhibition of autophagy diminishes apoptosis in human osteosarcoma cells.…”

Blockage of AMPK-ULK1 pathway mediated autophagy promotes cell apoptosis to increase doxorubicin sensitivity in breast cancer (BC) cells: an in vitro study

“…Autophagy is a evolutionarily conserved process for cells in defense of environmental stress, which degraded and reused the destructed cellular constitutes and cytoplasmic organelles to protect cells from death [13,14]. Recent data agreed that LC3 (microtubule-associated protein light chain 3) and p62 could be used to test autophagy activities, and increase of LC3-II (membrane bound)/LC3-I (cytosolic section), and degradation of p62 indicated activation of autophagy ux [15,16].…”