Molecular and Applied Mycology and Plant Pathology Laboratory, Department of Botany, University of Calcutta, Kolkata, WB, India.
Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER) Kolkata, Kolkata, WB, India.
IUBMB Life. 2019 Jul;71(7):992-1002. doi: 10.1002/iub.2047. Epub 2019 Apr 12.
Induction of apoptosis is the target of choice for modern chemotherapeutic treatment of cancer, where lack of potent "target-specific" drugs has led to extensive research on anticancer compounds from natural sources. In our study, we have used astrakurkurone, a triterpene isolated from wild edible mushroom, Astraeus hygrometricus. We have discussed the structure and stability of astrakurkurone employing single-crystal X-ray crystallography and studied its potential apoptogenicity in hepatocellular carcinoma (HCC) cells. Our experiments reveal that it is cytotoxic against the HCC cell lines (Hep 3B and Hep G2) at significantly low doses. Further investigations indicated that astrakurkurone acts by inducing apoptosis in the cells, disrupting mitochondrial membrane potential and inducing the expression of Bcl-2 family proteins, for example, Bax, and the downstream effector caspases 3 and 9. A molecular docking study also predicted direct interactions of the drug with antiapoptotic proteins Bcl-2 and Bcl-xL. Thus, astrakurkurone could become a valuable addition to the conventional repertoire of future anticancer drugs. © 2019 IUBMB Life, 1-11, 2019.
诱导细胞凋亡是现代癌症化学疗法的首选目标，由于缺乏有效的“靶向特异性”药物，人们广泛地从天然来源中研究抗癌化合物。在我们的研究中，使用了从野生食用蘑菇 Hygrophorus Astraeus 中分离出的三萜 astrakurkurone。我们采用单晶 X 射线晶体学讨论了 astrakurkurone 的结构和稳定性，并研究了其在肝癌 (HCC) 细胞中的潜在促凋亡作用。我们的实验表明，它在低剂量下对 HCC 细胞系 (Hep 3B 和 Hep G2) 具有细胞毒性。进一步的研究表明，astrakurkurone 通过诱导细胞凋亡、破坏线粒体膜电位以及诱导 Bcl-2 家族蛋白（如 Bax）和下游效应半胱天冬酶 3 和 9 的表达来发挥作用。分子对接研究还预测了药物与抗凋亡蛋白 Bcl-2 和 Bcl-xL 的直接相互作用。因此，astrakurkurone 可能成为未来抗癌药物常规方案的有价值的补充。© 2019 IUBMB Life，1-11，2019。
