Anti-metastatic Effects of Bee Venom and Melittin in Breast Cancer Cells by Upregulation of BRMS1 and DRG1 Genes

IF 3.2 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemical Biology & Drug Design Pub Date : 2024-10-13 DOI:10.1111/cbdd.14637

Nur Sena Sivri, Sinan Tetikoğlu, Sevgi Kolayli, Ammad Ahmad Farooqi, Selcen Çelik Uzuner

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Abstract

Apitherapy has started to gain tremendous recognition because of extraordinary pharmacological importance of honeybee-related ingredients and their derivatives. There has been a renewed interest in the bee venom–based therapies. Interdisciplinary researchers are studying the chemistry and translational value of venom for effective cancer treatment. Bee venom and its major component, melittin, are cytotoxic in cancer cells. In this study, MTT and scratch assays were performed for analysis of melittin-mediated antimetastatic effects. QPCR was used for expression profiling of metastasis-related genes. Three anti-metastatic genes (BRMS1, DRG1, and KAI1/CD82) were studied for the first time after bee venom and melittin treatment in MDA-MB-231 breast cancer cells compared with normal breast cells, and two prometastatic genes (EGFR and WNT7B) were also examined. KAI1/CD82 and BRMS1 are the negative regulators of EGFR. WNT7B is a negative regulator of KAI1/CD82. Selective cytotoxicity of bee venom and melittin was found to be higher as compared to cisplatin. Melittin induced an increase in the expression of BRMS1 and DRG1, whereas bee venom upregulated DRG1 and KAI1/CD82 expression in breast cancer. WNT7B was downregulated in bee venom–treated breast cancer cells. Results suggested that bee venom/melittin exerted antimetastatic effects primarily through upregulation of BRMS1, DRG1, and KAI1/CD82, and downregulation of WNT7B.

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蜂毒和 Melittin 通过上调 BRMS1 和 DRG1 基因对乳腺癌细胞的抗转移作用

由于蜜蜂相关成分及其衍生物具有非凡的药理作用，蜂疗已开始获得广泛认可。人们对以蜂毒为基础的疗法重新产生了兴趣。跨学科研究人员正在研究蜂毒在有效治疗癌症方面的化学和转化价值。蜂毒及其主要成分 Melittin 对癌细胞具有细胞毒性。在这项研究中，采用 MTT 和划痕法分析了美乐汀介导的抗转移作用。QPCR 被用于转移相关基因的表达谱分析。与正常乳腺癌细胞相比，首次研究了蜂毒和甜菊素处理 MDA-MB-231 乳腺癌细胞后的三个抗转移基因（BRMS1、DRG1 和 KAI1/CD82），同时还检测了两个前转移基因（表皮生长因子受体和 WNT7B）。KAI1/CD82 和 BRMS1 是表皮生长因子受体的负调控因子。WNT7B 是 KAI1/CD82 的负调控因子。与顺铂相比，蜂毒和美利汀的选择性细胞毒性更高。美利汀诱导乳腺癌中BRMS1和DRG1的表达增加，而蜂毒则上调DRG1和KAI1/CD82的表达。WNT7B在蜂毒处理的乳腺癌细胞中下调。结果表明，蜂毒/麦饭石素主要通过上调BRMS1、DRG1和KAI1/CD82以及下调WNT7B发挥抗转移作用。

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来源期刊

Chemical Biology & Drug Design 医学-生化与分子生物学

CiteScore

5.10

自引率

3.30%

发文量

164

审稿时长

4.4 months

期刊介绍： Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.