Research center of Environmental Pollutants, Qom University of Medical Sciences, Qom, Iran.
Department of Toxicology and Pharmacology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cutan Ocul Toxicol. 2023 Mar;42(1):12-18. doi: 10.1080/15569527.2022.2152041. Epub 2022 Dec 12.
Melanoma is known as an aggressive and highly lethal cancer. The poor prognosis and resistance to treatment are characteristics of melanoma. In melanoma cells, apoptosis signaling which relies heavily on the acute activity of mitochondria and reactive oxygen species (ROS) formation is suppressed. Studies have shown that compounds isolated from marine herbs and animals, have been shown to have cytotoxic consequences on cancerous cells in prior research. This study was designed to evaluate the apoptotic effect of methanolic extract of Persian Gulf shell-less marine mollusc (Peronia peronii) on skin mitochondria isolated from animal model of melanoma.
Melanoma mitochondria obtained from skin of melanoma animal model are studied in this research to see whether extracts from Persian Gulf shell-less marine mollusc , has a cytotoxic impact on them.
In this study, the mitochondria were isolated from melanoma cells via differential centrifugation were treated with various concentrations (650, 1300 and 2600 µg/ml) of methanolic extract of Peronia peronii. Then MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) viability assay, Reactive oxygen species (ROS) determination, Mitochondrial Membrane Potential (MMP) decline assay, mitochondrial swelling and cytochrome c release determination were performed. Flow cytometry assay of % apoptotic vs necrotic phenotypes was also performed on extract treated melanoma cells.
The results of MTT assay showed that different concentrations of extract significantly ( < 0.05) decreased the SDH activity in cancerous skin mitochondria with the IC50(1300 μg/ml). The ROS results also showed that all concentrations of extracts significantly increased ROS production, MMP decline and the release of cytochrome c in cancer groups mitochondria. The swelling of mitochondria was significantly increased compared to the control group. In addition, the results of apoptosis assay showed that addition of root extract of on melanoma cells increased apoptosis, while it had no effect on control non tumour cells.
Based on these results, the presence of potentially bioactive compounds in make this Persian Gulf coastal herb a strong candidate for further molecular studies and clinical research in the field of melanoma cancer therapy.
黑色素瘤是一种侵袭性和高度致命的癌症。预后不良和对治疗的耐药性是黑色素瘤的特征。在黑色素瘤细胞中，依赖于线粒体和活性氧（ROS）形成的急性活性的凋亡信号被抑制。研究表明，从海洋草药和动物中分离出的化合物在先前的研究中已显示出对癌细胞具有细胞毒性作用。本研究旨在评估来自波斯湾无壳海洋软体动物（Peronia peronii）的甲醇提取物对动物模型皮肤线粒体的凋亡作用。
本研究从黑色素瘤动物模型的皮肤中获得黑色素瘤线粒体，以研究来自波斯湾无壳海洋软体动物的提取物是否对其具有细胞毒性作用。
在这项研究中，通过差速离心从黑色素瘤细胞中分离出线粒体，并用不同浓度（650、1300 和 2600μg/ml）的 Peronia peronii 甲醇提取物处理。然后进行 MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）活力测定、活性氧（ROS）测定、线粒体膜电位（MMP）下降测定、线粒体肿胀和细胞色素 c 释放测定。还对提取物处理的黑色素瘤细胞进行了凋亡与坏死表型的%凋亡流式细胞术分析。
MTT 测定结果表明，不同浓度的提取物显著（<0.05）降低了癌症皮肤线粒体中的 SDH 活性，IC50（1300μg/ml）。ROS 结果还表明，所有浓度的提取物均显著增加了 ROS 的产生、癌症组线粒体中 MMP 的下降和细胞色素 c 的释放。与对照组相比，线粒体肿胀明显增加。此外，凋亡分析的结果表明，根提取物的添加增加了黑色素瘤细胞的凋亡，而对非肿瘤细胞没有影响。
基于这些结果，表明波斯湾沿海草药中存在潜在的生物活性化合物，使这种草药成为黑色素瘤癌症治疗领域进一步分子研究和临床研究的有力候选者。
