Background: Bee venom is a promising agent for cancer treatment due to its selective cytotoxic potential for cancer cells through apoptotic pathways. However, there is no evidence for changes in the epigenome and mitochondrial DNA copy numbers after bee venom application. The purpose of this study was to determine the impact of bee venom on cytosine modifications and mitochondrial DNA copy number variation.

Methods: A broad range of methods was applied to elucidate the impact of bee venom on neoplastic cells. These included MTT assay for detection of cytotoxicity, immunostaining of cytosine modifications and mitochondria, assessment of cellular morphology by flow cytometry, and quantification of mitochondrial DNA copy numbers using QPCR.

Results: Bee venom-induced cell death was selective for cancer cells, where it triggered a response characterized by alteration of cytosine modification. In contrast, normal cells were more resistant to DNA modifications. Furthermore, application of the venom resulted in variation of mitochondrial membrane permeability and mitochondrial DNA copy numbers, together with alterations in cell morphology, manifesting as reduced affected cell size.

Conclusion: The study findings suggest that bee venom can be used as a selective DNA (de)methylating agent in cancer. Various agents (such as decitabine and 5-azacytidine) have been synthesized and developed for cancer treatment, and a range of syntheses and preparation and application methods have been described for these patented drugs. However, to the best of our knowledge, no previous research has investigated the use of bee venom or any component thereof for epigenetic therapy in cancer cells.

背景：蜂毒是一种很有前途的癌症治疗药物，因为它通过凋亡途径对癌细胞产生选择性细胞毒作用。然而，没有证据表明蜂毒应用后表观基因组和线粒体 DNA 拷贝数发生变化。本研究的目的是确定蜂毒对胞嘧啶修饰和线粒体 DNA 拷贝数变异的影响。

方法：应用广泛的方法来阐明蜂毒对肿瘤细胞的影响。这些包括用于检测细胞毒性的 MTT 测定、胞嘧啶修饰和线粒体的免疫染色、通过流式细胞术评估细胞形态以及使用 QPCR 量化线粒体 DNA 拷贝数。

结果：蜂毒诱导的细胞死亡对癌细胞具有选择性，它触发了以改变胞嘧啶修饰为特征的反应。相比之下，正常细胞对 DNA 修饰的抵抗力更强。此外，毒液的应用导致线粒体膜通透性和线粒体 DNA 拷贝数的变化，以及细胞形态的改变，表现为受影响的细胞大小减少。

结论：研究结果表明，蜂毒可用作癌症中的选择性 DNA（去）甲基化剂。各种药物（如地西他滨和5-氮杂胞苷）已被合成和开发用于癌症治疗，并描述了这些专利药物的一系列合成、制备和应用方法。然而，据我们所知，以前没有研究调查过使用蜂毒或其任何成分在癌细胞中进行表观遗传治疗。