The Multifaceted Role of Flavonoids in Cancer Therapy: Leveraging Autophagy with a Double-Edged Sword

Abstract

Flavonoids are considered as pleiotropic, safe, and readily obtainable molecules. A large number of recent studies have proposed that flavonoids have potential in the treatment of tumors by the modulation of autophagy. In many cases, flavonoids suppress cancer by stimulating excessive autophagy or impairing autophagy flux especially in apoptosis-resistant cancer cells. However, the anti-cancer activity of flavonoids may be attenuated due to the simultaneous induction of protective autophagy. Notably, flavonoids-triggered protective autophagy is becoming a trend for preventing cancer in the clinical setting or for protecting patients from conventional therapeutic side effects in normal tissues. In this review, focusing on the underlying autophagic mechanisms of flavonoids, we hope to provide a new perspective for clinical application of flavonoids in cancer therapy. In addition, we highlight new research ideas for the development of new dosage forms of flavonoids to improve their various pharmacological effects, establishing flavonoids as ideal candidates for cancer prevention and therapy in the clinic.

Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways

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Novel Therapeutic Strategies for Ischemic Stroke: Recent Insights into Autophagy

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Potential Therapeutic Action of Autophagy in Gastric Cancer Managements: Novel Treatment Strategies and Pharmacological Interventions

“…Autophagy can be used to sensitize tumor cells to chemotherapy or radiation, therapy blocking its cytoprotective action, which leads to the destruction of antiapoptotic cells via autophagy (Gupta et al, 2021). Through the use of their mechanisms, autophagy demonstrated resistance to chemotherapy and radiotherapy, and it also hinders the effectiveness of anticancer medicine (Zhang et al, 2021). Inhibiting autophagy in cancerous cells can have adverse repercussions on the body, including such mitochondrial dysfunction, redox imbalance, nucleotide consumption, and reduction of energy supply (Poillet-Perez et al, 2021).…”