Focusing on the Role of Natural Products in Overcoming Cancer Drug Resistance: An Autophagy-Based Perspective

Abstract

Autophagy is a critical cellular adaptive response in tumor formation. Nutritional deficiency and hypoxia exacerbate autophagic flux in established malignancies, promoting tumor cell proliferation, migration, metastasis, and resistance to therapeutic interventions. Pro-survival autophagy inhibition may be a promising treatment option for advanced cancer. Furthermore, excessive or persistent autophagy is cytotoxic, resulting in tumor cell death. Targeted autophagy activation has also shown significant promise in the fight against tumor drug resistance. Several research groups have examined the ability of natural products (NPs) such as alkaloids, terpenoids, polyphenols, and anthraquinones to serve as autophagy inhibitors or activators. The data support the capacity of NPs that promote lethal autophagy or inhibit pro-survival autophagy from being employed against tumor drug resistance. This paper discusses the potential applications of NPs that regulate autophagy in the fight against tumor drug resistance, some limitations of the current studies, and future research needs and priorities.

The Role of Autophagy and Apoptosis in the Combined Action of Plasma-Treated Saline, Doxorubicin, and Medroxyprogesterone Acetate on K562 Myeloid Leukaemia Cells

“…In the second case, the cell has a chance to clean up and survive if the damage to the organelles is relatively limited. An important research area in modern oncology is the inhibition of the autophagy mechanism and the initiation of apoptosis [ 44 , 45 ]. Some studies on acute myeloid leukaemia, however, suggest that cancer cell differentiation is stimulated through the initiation of autophagy [ 46 ].…”

Nanomedicine Strategies in Conquering and Utilizing the Cancer Hypoxia Environment

“…Feng et al found that the level of the miR-27a expression was obviously elevated under hypoxia and improved paclitaxel resistance by restricting the expression of APAF1 . Cell autophagy is a highly conserved biological process that breaks down and reuses long-lived organelles or damaged, misfolded proteins, which can lower cancer cell susceptibility to therapeutic reagents in various types of human cancer and be induced in solid hypoxia tumors and play a prosurvival role . Hypoxia-induced autophagy increases tumor cell lifetime, promotes a more destructive phenotype, and increases the risk of metastasis.…”

“…113 Cell autophagy is a highly conserved biological process that breaks down and reuses long-lived organelles or damaged, misfolded proteins, which can lower cancer cell susceptibility to therapeutic reagents in various types of human cancer and be induced in solid hypoxia tumors and play a prosurvival role. 114 Hypoxia-induced autophagy increases tumor cell lifetime, promotes a more destructive phenotype, and increases the risk of metastasis. In addition, hypoxia-induced autophagy increases tumor cell resistance to cancer therapy.…”

Lenvatinib resistance mechanism and potential ways to conquer

“…Autophagy is regarded as an adaption way for tumor cells to survival along with long time evolution. Herein, it has been certified to play a double-edged sword in drug resistance ( Smith and Macleod, 2019 ; Yao et al, 2022 ). On one hand, autophagy participates in the development of drug resistance and protects cancer cells from chemotherapeutics ( Gao et al, 2022 ).…”