Mushrooms as potent autophagy modulators in cancer therapy: Current evidence and therapeutic prospects
Md. Mahmudul Hasan, Eva Azme, Rashedul Alam, Md. Jahirul Islam Mamun, Md. Tanvir Chowdhury, Md. Rasel, Md. Safayat Hossen Momen, Neamul Hoque, Md. Ekramul Haque Ekram, Nazmul Hasan Eshaque, Shakil Ahmed, Md. Tashrif Rahman Tipu, Sanjida Shahid Juthi, Mohammad Fazlul Kabir, Ahsan Ullah, Md. Liakot Ali, S. M. Moazzem Hossen, Hea‐Jong Chung
Abstract
Mushrooms, recognized for their culinary and medicinal applications, are emerging as potential sources of autophagy modulators in cancer treatment. Autophagy is cellular degradation triggered by organelle damage, protein aggregation, metabolic disturbances, or nutrient scarcity. It contributes to the suppression of early tumor development and the promotion of cancer cell survival at advanced stages. This review systematically assesses the current evidence on the anticancer potential of mushrooms and their bioactive compounds, focusing on their ability to modulate autophagy. The review lists over 18 mushroom species (e.g., Ganoderma lucidum, Cordyceps, Phellinus) and 28 bioactive compounds (such as Ganoderic acid DM, Cordycepin, Hispidin ) that affect autophagy, demonstrating efficacy against 15 cancer types, including colorectal, lung, breast, and liver cancers. Essential compounds modulate autophagy through phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and Beclin-1 pathways, resulting in notable anticancer effects. G. lucidum extracts quantitatively reduced colorectal tumor growth by up to 60% in vivo . Additionally, Cordycepin induced autophagic cell death in lung cancer cells, with IC 50 values as low as 25 μmol/L.The findings highlight the potential of mushrooms as low-toxicity adjuvants to conventional therapies, providing advantages such as immune modulation and antioxidant activity. Mushrooms and their bioactive components present promising avenues for cancer therapy through the modulation of autophagy. The context-dependent effects of autophagy, along with the limited clinical evidence, present considerable challenges. Future clinical trials must focus on developing standardized extracts and personalized approaches to effectively translate this potential into clinical practice. • Mushroom compounds (e.g., GA- DM, Cordycepin) modulate autophagy via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK) in 15 types of cancers. • Mushroom compounds target autophagy's dual cancer role (early suppression, late promotion) for context-specific therapy. • Ganoderma lucidum and Antrodia cinnamomea modulate autophagy preclinically, boost chemo sensitivity in colorectal, lung and breast cancer. • Mushrooms synergize with standard therapies via autophagy modulation. • Clinical trials and standardized extracts preparation are needed to use the mushroom's autophagy potential in cancer therapies.