Department of Pharmaceutical Biochemistry, Medical University of Bialystok, Mickiewicza 2A, 15-222 Białystok, Poland.
Mar Drugs. 2024 Jul 15;22(7):315. doi: 10.3390/md22070315.
Malignant melanoma-a tumor originating from melanocytes-is characterized by dynamic growth and frequent metastases in the early stage of development. Current therapy methods are still insufficient, and there is a need to search for new ways of treating this malady. The induction of apoptosis-physiological cell death-by proteasome inhibitors is recognized as an effective method of non-invasive elimination of cancer cells. In our research, we wanted to check the potential of marizomib (MZB, salinosporamide A, NPI-0052)-an irreversible proteasome inhibitor derived from the marine actinomycete -to induce apoptosis in A375 and G361 malignant melanoma cells. We determined the cytotoxic activity of marizomib by performing an MTT test. Ethidium bromide and acridine orange staining demonstrated the disruption of membrane integrity in the examined cell lines. We confirmed the proapoptotic activity of marizomib by flow cytometry with the use of an FITC-Annexin V assay. A Western blot analysis presented an increase in the expression of proteins related to endoplasmic reticulum (ER) stress as well as markers of the apoptosis. The gathered findings suggest that marizomib induced the ER stress in the examined melanoma cancer cells and directed them towards the apoptosis pathway.
恶性黑素瘤——一种起源于黑素细胞的肿瘤——其特征是在早期阶段具有动态生长和频繁转移。目前的治疗方法仍然不足，需要寻找治疗这种疾病的新方法。蛋白酶体抑制剂诱导细胞凋亡——生理细胞死亡——被认为是一种非侵入性消除癌细胞的有效方法。在我们的研究中，我们想检查马利佐米（MZB，来源于海洋放线菌的 Salinosporamide A，NPI-0052）——一种不可逆的蛋白酶体抑制剂——在诱导 A375 和 G361 恶性黑素瘤细胞凋亡方面的潜力。我们通过 MTT 试验测定了马利佐米的细胞毒性活性。溴化乙锭和吖啶橙染色显示了所检查的细胞系中膜完整性的破坏。我们通过使用 FITC-Annexin V 测定法通过流式细胞术证实了马利佐米的促凋亡活性。Western blot 分析显示内质网 (ER) 应激相关蛋白以及凋亡标志物的表达增加。收集到的研究结果表明，马利佐米诱导了所检查的黑素瘤癌细胞中的 ER 应激，并促使它们走向凋亡途径。
