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通过生成差异活性氧诱导从 中分离的三萜类化合物诱导人膀胱癌细胞凋亡。

Induction of apoptosis in human bladder cancer cells by triterpenoids isolated from through differential reactive oxygen species generation.

机构信息

Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.

出版信息

Nat Prod Res. 2021 Dec;35(24):5629-5636. doi: 10.1080/14786419.2020.1819272. Epub 2020 Sep 21.

Abstract

A novel triterpenoid, holarol,3β-lup-20(31)-en-3,29,30-triol along with one triterpenoid, dihydrocanaric acid() and one known pentacyclic triterpenoid, betulin have been isolated from (L.)Wall The structures of the compounds were elucidated by extensive IR, 1D, 2D NMR and mass spectrometric analysis. The optimised geometry of was calculated by density-functional theory (DFT) using M06-2X hybrid functional and 6-31 G(D) basis set. The compounds showed differential cytotoxic activities in the cell lines-HeLa, EAC, Raji and T24. -triterpenoid showed highest sensitivity (IC: 1.710 μg/mL) against the bladder cancer cell line T24 followed by (IC 9.698 µg/mL) and (IC 11.769 µg/mL). Compound showed highest reactive oxygen species (ROS) generation in T24 cell line followed by and resulting in induction of apoptosis through activation of caspase, cleavage of PARP and reduction of Bcl-2/Bax ratio. Thus compounds , along with could be potent anticancer agents.

摘要

从 (L.)Wall 中分离得到了一种新的三萜类化合物 holarol、3β-lup-20(31)-en-3、29、30-三醇,以及一种三萜类化合物二氢卡纳酸和一种已知的五环三萜类化合物白桦脂醇。通过广泛的 IR、1D、2D NMR 和质谱分析确定了化合物的结构。通过密度泛函理论(DFT)使用 M06-2X 混合函数和 6-31G(D)基组计算了 的优化几何形状。这些化合物在细胞系-HeLa、EAC、Raji 和 T24 中表现出不同的细胞毒性活性。三萜类化合物 对膀胱癌细胞系 T24 的敏感性最高(IC:1.710μg/mL),其次是 (IC 9.698μg/mL)和 (IC 11.769μg/mL)。化合物 在 T24 细胞系中产生最高的活性氧(ROS)生成,其次是 和 ,通过激活 caspase、PARP 切割和降低 Bcl-2/Bax 比值诱导细胞凋亡。因此,化合物 、 以及 可能是有效的抗癌药物。

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