Division of Toxicology, Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia.
Department of Medical Biochemistry, Faculty of Medicine, University of Latvia, 1004 Riga, Latvia.
Toxins (Basel). 2024 Feb 29;16(3):117. doi: 10.3390/toxins16030117.
Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and venom has been studied the most extensively. Numerous studies dealing with the positive assets of bee venom (BV) indicated its beneficial properties. The usage of bee products to prevent the occurrence of diseases and for their treatment is often referred to as apitherapy and is based mainly on the experience of the traditional system of medical practice in diverse ethnic communities. Today, a large number of studies are focused on the antitumor effects of BV, which are mainly attributed to its basic polypeptide melittin (MEL). Previous studies have indicated that BV and its major constituent MEL cause a strong toxic effect on different cancer cells, such as liver, lung, bladder, kidney, prostate, breast, and leukemia cells, while a less pronounced effect was observed in normal non-target cells. Their proposed mechanisms of action, such as the effect on proliferation and growth inhibition, cell cycle alterations, and induction of cell death through several cancer cell death mechanisms, are associated with the activation of phospholipase A (PLA), caspases, and matrix metalloproteinases that destroy cancer cells. Numerous cellular effects of BV and MEL need to be elucidated on the molecular level, while the key issue has to do with the trigger of the apoptotic cascade. Apoptosis could be either a consequence of the plasmatic membrane fenestration or the result of the direct interaction of the BV components with pro-apoptotic and anti-apoptotic factors. The interaction of BV peptides and enzymes with the plasma membrane is a crucial step in the whole process. However, before its possible application as a remedy, it is crucial to identify the correct route of exposure and dosage of BV and MEL for potential therapeutic use as well as potential side effects on normal cells and tissues to avoid any possible adverse event.
在替代医学和东方医学中使用的各种天然化合物中，从不同生物体中分离出的毒素已经应用了多年，其中毒液的研究最为广泛。大量研究表明蜜蜂毒液 (BV) 具有有益特性。使用蜂产品预防疾病和治疗疾病通常被称为蜂疗，主要基于不同民族社区传统医学实践体系的经验。如今，大量研究集中在 BV 的抗肿瘤作用上，这主要归因于其基本多肽蜂毒素 (MEL)。先前的研究表明，BV 和其主要成分 MEL 对不同的癌细胞，如肝癌、肺癌、膀胱癌、肾癌、前列腺癌、乳腺癌和白血病细胞，具有很强的毒性作用，而对正常非靶细胞的作用则不明显。它们的作用机制，如对增殖和生长抑制、细胞周期改变以及通过几种癌细胞死亡机制诱导细胞死亡的影响，与激活磷脂酶 A (PLA)、半胱天冬酶和基质金属蛋白酶有关，这些酶会破坏癌细胞。BV 和 MEL 的许多细胞效应需要在分子水平上阐明，而关键问题与凋亡级联的触发有关。凋亡可能是质膜窗孔的结果，也可能是 BV 成分与促凋亡和抗凋亡因子直接相互作用的结果。BV 肽和酶与质膜的相互作用是整个过程的关键步骤。然而，在将其作为治疗方法应用之前，必须确定 BV 和 MEL 的正确暴露途径和剂量，以用于潜在的治疗用途，以及对正常细胞和组织的潜在副作用，以避免任何可能的不良事件。
