Neoergosterol-rich mushroom extract, resourced from wild edible mushroom Termitomyces heimii Natarajan, induces robust apoptosis against lung cancer

• Published in: South African journal of botany 2024-07, Vol.170, p.229-249
• Main Authors: Ray, Ribhu, Saha, Saparja, Pyne, Nibedita, Pal, Amrita, Paul, Santanu
• Format: Article
• Language: English
• Subjects: A549; antineoplastic agents; apoptosis; botany; cancer therapy; cell movement; computer simulation; drug development; Isoptera; lung neoplasms; metabolomics; methanol; mitochondrial membrane; Mushroom; mushrooms; Neoergosterol; neoplasm cells; Non-small cell lung cancer; Termitomyces; Termitomyces heimii Natarajan; toxicity testing
• ISSN: 0254-6299
• DOI: 10.1016/j.sajb.2024.05.029

The non-specificity of conventional cancer drugs imposes a significant obstacle in cancer treatment, so the development of a safe anti-cancer alternative by methodologically revisiting several traditional medicinal systems may be a possible way to get rid of this problem. Therefore, the present study evaluates the anti-cancer potentiality of one of the Asiatic and African regions’ widely popular edible and ethnobotanically significant termite mushroom, Termitomyces heimii Natarajan (T. heimii), against various cancers. The anti-proliferative and chemo-preventive potentiality of two different extracts of T. heimii was evaluated against a panel of eight cancer cell lines and normal cells through an MTT assay. In vitro screening highlights that the methanolic extract of T. heimii had the highest anti-proliferative potential against A549 cells and had a negligible effect on normal cells. The extract specifically induced robust apoptosis in A549 cells through augmentation of intracellular ROS, disrupting mitochondrial membrane polarity, thus ultimately resulting in caspase-dependent apoptosis in lung cancer cells. Post-treatment, down-regulation of anti-apoptotic BCL-2 coordinated up-regulation of BAX expression, and an elevated expression of p53 signified the p53-dependent apoptosis. Moreover, the mushroom extract restricted cellular migration in the palladin-dependent pathway by downregulating the expression of PALLADIN. LC-MS-based metabolomic profiling was conducted to identify the potential anti-cancer mycocompounds in the methanol extract. The metabolomic profiling analysis, followed by an in silico molecular docking study, identified a unique mycosterol, neoergosterol, as a possible anti-cancer compound in the mushroom extract. The present study concludes a novel mycocompound neoergosterol resourcing from Termitomyces heimii Natarajan, demonstrating selective robust apoptosis against non-small cell lung cancer cells and also provides a chemoprotective shield against normal cells, which holds great promise for future drug development to treat lung cancer. [Display omitted] •Introducing a novel wild edible mushroom, Termitomyces heimii Natarajan, to the mycophagy communities of Asia and Africa, emphasizing its anti-cancer effect against lung cancer.•The Neoergosterol-rich mushroom extract significantly attenuated lung cancer progression by modulating the p53 pathway, resulting in ROS-substantiated, caspase-dependent, robust apoptosis in lung cancer cells.•