Arast Yalda, Sabbaghi Mahya, Kamranfar Farzane, Heidari Fatemeh, Fazli Nejad Seyed Mojtaba, Hosseinabadi Tahereh, Pourahmad Jalal
Research Center of Environmental Pollutants, Qom University of Medical Sciences, Qom, Iran.
Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences Tehran, Tehran, Iran.
Cutan Ocul Toxicol. 2024 Dec;43(4):264-271. doi: 10.1080/15569527.2024.2389193. Epub 2024 Aug 14.
Melanoma is known as a highly lethal cancer. In melanoma cells, apoptosis signalling which relies heavily on the acute activity of mitochondria and reactive oxygen species (ROS) formation is suppressed. Our previous studies on natural compounds on melanoma suggested that mitochondria are a potential target for the melanoma treatment by selective cytotoxic effect of them. The black soldier fly is an important environmental protectant insect that based on recent studies induces apoptosis in liver and colorectal carcinoma cells through the activation of caspase 3, 8, and 9 and ultimately inhibits the growth of cancer cells.
This study was designed to evaluate the selective apoptotic effect of the n-hexane BSFL extract (BSFLE) on skin mitochondria.
The mitochondria isolated from melanoma cells were treated with various concentrations (1500, 3000, and 6000 µg/ml) of n-hexane BSFLE Then MTT viability assay, ROS determination, Mitochondrial Membrane Potential (MMP), mitochondrial swelling, cytochrome c release determination, and % apoptosis were performed.
MTT assay showed that different concentrations of n-hexane BSFLE significantly ( < 0.05) decreased the SDH activity in cancerous skin mitochondria with the IC50. The ROS production and mitochondrial swelling results also showed that all concentrations of BSFL extracts significantly increased. MMP decline and the release of cytochrome c in cancer groups mitochondria. BSFLE increased apoptosis on melanoma cells.
It is suggested that n-hexane BSFLE compounds selectively induce a cascade of proapoptotic events that are probably defective in cancer cells. Most of these compounds target the mitochondrial transient pore caused by disruption of the mitochondrial respiratory chain. These events lead to disruption of the temporary permeability of mitochondria, swelling of mitochondria and finally the formation of apoptosome in the cytosol.
黑色素瘤是一种高致死性癌症。在黑色素瘤细胞中，严重依赖线粒体急性活性和活性氧（ROS）形成的凋亡信号传导受到抑制。我们之前关于黑色素瘤天然化合物的研究表明，线粒体是通过它们的选择性细胞毒性作用来治疗黑色素瘤的潜在靶点。黑水虻是一种重要的环保昆虫，根据最近的研究，它通过激活半胱天冬酶3、8和9诱导肝癌和结肠癌细胞凋亡，并最终抑制癌细胞生长。
本研究旨在评估正己烷黑水虻幼虫提取物（BSFLE）对皮肤线粒体的选择性凋亡作用。
用不同浓度（1500、3000和6000μg/ml）的正己烷BSFLE处理从黑色素瘤细胞中分离出的线粒体。然后进行MTT活力测定、ROS测定、线粒体膜电位（MMP）、线粒体肿胀、细胞色素c释放测定和凋亡率测定。
MTT分析表明，不同浓度的正己烷BSFLE显著（<0.05）降低了癌性皮肤线粒体中的SDH活性，IC50值出现。ROS产生和线粒体肿胀结果还表明，所有浓度的BSFL提取物均显著增加。癌症组线粒体中MMP下降和细胞色素c释放。BSFLE增加了黑色素瘤细胞的凋亡。
表明正己烷BSFLE化合物选择性地诱导一系列促凋亡事件，这些事件在癌细胞中可能存在缺陷。这些化合物中的大多数靶向由线粒体呼吸链破坏引起的线粒体瞬时孔。这些事件导致线粒体暂时通透性的破坏、线粒体肿胀，最终在细胞质中形成凋亡小体。
