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灵芝(担子菌纲)提取物介导的细胞凋亡在乳腺癌细胞中的抗癌活性。

Apoptosis-Mediated Anticancer Activity of Ganoderma colossus (Agaricomycetes) Extracts in Breast Cancer Cells.

机构信息

Department of Biosciences, Mangalore University, Mangalagangothri - 574 199, Karnataka, India.

Cell Biology and Molecular Genetics Division, Yenepoya Research Centre, Yenepoya (Deem to be University), Deralakatte Mangaluru 575018, Karnataka, India.

出版信息

Int J Med Mushrooms. 2023;25(10):23-37. doi: 10.1615/IntJMedMushrooms.2023049907.

DOI:10.1615/IntJMedMushrooms.2023049907
PMID:37830194
Abstract

Cancer is a leading cause of death worldwide. The current cancer treatments including chemo-, radio- and immuno-therapies pose various side effects, and chances of recurrence that demand for new therapeutics to overcome the issues with existing ones. Mushrooms are considered a potential source of novel therapeutic agents. Ganoderma colossus, a non-edible wood-inhabiting mushroom, is known for certain medical properties. The present study aimed to investigate the possible anticancer activity of methanolic, ethyl acetate, and chloroform extracts of G. colossus, against MCF-7 cells and the mechanism of action(s). MTT assay and gene expression studies were carried out by following the standard protocols. The results demonstrated that among the three solvents, the ethyl acetate crude extract of the mushroom exhibited potential cytotoxic activity on MCF-7 (IC50, 17.2 ± 2.7). The DNA damage induced by the solvent extracts of G. colossus was observed by H2AX foci formation. The TP53 over-expression and flow cytometry analysis indicated that checkpoint activation followed by cell cycle arrest occurred at G1/G0 phase in response to the extract treatment. The dual acridine orange/ethidium bromide (AO/EB) staining revealed apoptosis-associated changes in the cells. Analysis of caspase 3 activations by immunophenotyping confirmed the apoptotic process in the extract-treated cells. Bcl-2 and TP53 mRNA expression data by RT-PCR disclosed the apoptosis pathway. The GC- MS spectral data of the ethyl acetate crude extract of the mushroom indicated the presence of molecules capable of inducing apoptosis. The present study warrants further studies to isolate the molecule(s) from G. colossus which may be a potential drug candidate for breast cancers.

摘要

癌症是全球主要的死亡原因。目前的癌症治疗方法包括化疗、放疗和免疫疗法,这些方法都存在各种副作用和复发的可能性,因此需要新的治疗方法来克服现有方法存在的问题。蘑菇被认为是新型治疗剂的潜在来源。巨芝,一种非食用的木栖蘑菇,具有一定的药用特性。本研究旨在研究巨芝甲醇、乙酸乙酯和氯仿提取物对 MCF-7 细胞的可能抗癌活性及其作用机制。按照标准方案进行了 MTT 测定和基因表达研究。结果表明,在三种溶剂中,蘑菇的乙酸乙酯粗提取物对 MCF-7 具有潜在的细胞毒性活性(IC50,17.2±2.7)。通过 H2AX 焦点形成观察到巨芝溶剂提取物诱导的 DNA 损伤。TP53 过表达和流式细胞术分析表明,提取物处理后会发生细胞周期阻滞,导致细胞周期停滞在 G1/G0 期,从而激活检查点。吖啶橙/溴化乙锭(AO/EB)双重染色显示细胞凋亡相关变化。通过免疫表型分析对 caspase 3 活化的分析证实了提取物处理细胞中的凋亡过程。RT-PCR 分析 Bcl-2 和 TP53 mRNA 表达数据揭示了凋亡途径。蘑菇乙酸乙酯粗提取物的 GC-MS 谱数据表明存在能够诱导细胞凋亡的分子。本研究进一步研究从巨芝中分离可能成为乳腺癌潜在药物候选物的分子是有必要的。

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