Role of lupeol in chemosensitizing therapy-resistant prostate cancer cells by targeting MYC, β-catenin and c-FLIP: in silico and in vitro studies.

In Silico Pharmacology Pub Date : 2022-01-01 DOI:10.1007/s40203-022-00131-3

Santosh Kumar Maurya, Homa Fatma, Akhilesh Kumar Maurya, Nidhi Mishra, Hifzur R Siddique

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引用次数: 4

Abstract

Prostate cancer (CaP) is one of the most frequent malignancies amongst men. Enzalutamide is the second-generation potent androgen receptor (AR) antagonist used against metastatic and non-metastatic CaP. Unfortunately, the development of chemoresistance in cancer cells reduces the effectiveness of Enzalutamide. Lupeol is a pentacyclic triterpene found in different fruits, vegetables, and medicinal plants and possesses anti-inflammatory and anti-cancer properties. Here, we report in silico and in vitro studies of Lupeol and Enzalutamide against the β-CATENIN, c-FLIP_L, and c-MYC, which play a significant role in chemoresistance. We observed that Lupeol significantly inhibits the cell growth of chemoresistant Du145 cells and cancer stem cells (CSCs) either alone or in combination with Enzalutamide. Lupeol and Enzalutamide were also found to dock with β-CATENIN, c-FLIP_L, and c-MYC. The following MD simulation data showed both compounds exerting structural changes in these proteins. Finally, they significantly inhibit the transcriptional activity of all these genes, as observed by luciferase assay. Thus, we infer that Lupeol chemosensitizes the CaP cells for Enzalutamide-resistant CaP cells.

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通过靶向MYC、β-catenin和c-FLIP对化疗耐药前列腺癌细胞增敏的作用:在硅和体外研究

前列腺癌(CaP)是男性最常见的恶性肿瘤之一。Enzalutamide是第二代雄激素受体(AR)拮抗剂，用于治疗转移性和非转移性CaP。不幸的是，癌细胞中化学耐药的发展降低了Enzalutamide的有效性。Lupeol是一种五环三萜，存在于不同的水果、蔬菜和药用植物中，具有抗炎和抗癌的特性。在这里，我们报道了Lupeol和Enzalutamide对β-CATENIN, c-FLIPL和c-MYC的硅和体外研究，这些基因在化疗耐药中起重要作用。我们观察到，无论是单独使用还是与Enzalutamide联合使用，Lupeol都能显著抑制化疗耐药Du145细胞和癌症干细胞(CSCs)的细胞生长。Lupeol和Enzalutamide也被发现与β-CATENIN, c-FLIPL和c-MYC对接。下面的MD模拟数据显示，这两种化合物对这些蛋白质产生了结构变化。最后，通过荧光素酶分析发现，它们显著抑制了所有这些基因的转录活性。因此，我们推断Lupeol对enzalutamide耐药的CaP细胞具有化学增敏作用。图形化的简介:

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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In Silico Pharmacology

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