The membrane effects of melittin on gastric and colorectal cancer

The cytotoxic effects of melittin, a bee-venom peptide, have been widely studied towards cancer cells. Typically, these studies have examined the effect of melittin over extended-time courses (6–24 hours), meaning that immediate cellular interactions have been overlooked. In this work, we demonstrate the rapid effects of melittin on both gastric and colorectal cancer, specifically AGS, COLO205 and HCT-15 cell lines, over a period of 15 minutes. Melittin exhibited a dose dependent effect at 4 hours of treatment, with complete cellular death occurring at the highest dose of 20 μg/mL. Interestingly, when observed at shorter time points, melittin induced cellular changes within seconds; membrane damage was observed as swelling, breakage or blebbing. High-resolution imaging revealed treated cells to be compromised, showing clear change in cellular morphology. After 1 minute of melittin treatment, membrane changes were observed, and intracellular material could be seen expelled from the cells. Overall, these results enhance our understanding of the fast acting anti-cancer effects of melittin.

蜂毒肽（melittin）作为一种蜂源多肽，其针对癌细胞的细胞毒性效应已得到广泛研究。既往此类研究多聚焦于6~24小时的长时间干预周期下的蜂毒肽作用效果，这使得对其与细胞的即刻相互作用效应的探究被长期忽视。本研究以胃癌与结直肠癌细胞——具体为AGS、COLO205及HCT-15细胞系——为研究对象，揭示了蜂毒肽在15分钟干预周期内的快速作用效应。在给药处理4小时后，蜂毒肽呈现出明确的剂量依赖性杀伤效应，当给药剂量达到20 μg/mL的最高值时，可实现细胞完全死亡。值得注意的是，在更短的时间节点下观察时，蜂毒肽可在数秒内诱导细胞发生形态改变：细胞膜损伤表现为细胞肿胀、破裂或胞膜起泡。高分辨率成像结果显示，经蜂毒肽处理的细胞完整性遭到破坏，细胞形态出现显著变化。在给药处理1分钟后即可观察到细胞膜发生改变，且可观测到细胞内物质被排出胞外。综上，本研究结果深化了我们对蜂毒肽快速抗癌作用的认知。