Zilakova Simona, Gavurova Martina, Sebova Dominika, Goga Michal, Backor Martin, Medvecova Viktoria, Kecsey Dajana, Kello Martin
Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, Trieda SNP 1, 040 11, Košice, Slovakia.
Department of Plant Biology, Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University, 041 67, Košice, Slovakia.
Med Oncol. 2025 Jul 17;42(8):341. doi: 10.1007/s12032-025-02890-3.
Cyanobacteria have long attracted scientific interest through their potential application in the development of new therapeutic approaches, particularly those related to the treatment of cancer. In this study, the antiproliferative effects of Nostoc commune extract (NOS) and the cyanobacterial compound scytonemin (SCY) were evaluated against a variety of in vitro cancer models, including cervix, colon, breast, lung, and leukemia cell lines, using resazurin assays. Both of the studied compounds were found to have inhibited metabolic activity in a dose-dependent manner, with IC values ranging from 60.5 to 462.0 µM for SCY and 157.0 to 740.3 µM for NOS. SCY displayed higher levels of inhibitory activity than NOS against all of the tested cancer models, but was particularly effective against HL-60 and Jurkat leukemia cells, with IC values recorded as 60.5 µM and 88.2 µM, respectively. However in contrast, the two compounds exhibited significantly lower levels of inhibition against non-cancerous MCF-10A and BJ-5ta cells. Flow cytometry studies of leukemia cells treated with SCY revealed that the compound had effectively inhibited cell proliferation over prolonged periods; HL-60 cells displayed G1 phase arrest which lasted for 48 h, while an accumulated G0/G1 sub-population was detected in Jurkat cells, as indicator of apoptosis. Further analysis of cells treated with SCY observed reduced levels of Rb protein and an increase in p21 expression in both HL-60 and Jurkat cell lines. Apoptotic markers such as phosphatidylserine externalization were observed, and mitochondrial dysfunction characterized by the dissipation of mitochondrial membrane potential was also detected. SCY activated the mitochondrial apoptotic pathway, inducing cytochrome c release and subsequent caspase-9, -3, and -7 activation. Finally, PARP cleavage, a typical marker of apoptosis, was identified in both leukemia cell lines following treatment with SCY. The findings suggest that SCY induces apoptosis in leukemia cells through the activation of the mitochondrial pathway, highlighting its potential for development as a future anti-cancer agent.
蓝藻长期以来因其在开发新治疗方法，特别是与癌症治疗相关方法中的潜在应用而吸引了科学界的关注。在本研究中，使用刃天青测定法评估了普通念珠藻提取物（NOS）和蓝藻化合物scytonemin（SCY）对多种体外癌症模型的抗增殖作用，这些模型包括子宫颈、结肠、乳腺、肺和白血病细胞系。研究发现，这两种化合物均以剂量依赖性方式抑制代谢活性，SCY的IC值范围为60.5至462.0 μM，NOS的IC值范围为157.0至740.3 μM。在所有测试的癌症模型中，SCY的抑制活性水平均高于NOS，但对HL-60和Jurkat白血病细胞特别有效，其IC值分别记录为60.5 μM和88.2 μM。然而，相比之下，这两种化合物对非癌性MCF-10A和BJ-5ta细胞的抑制水平明显较低。对用SCY处理的白血病细胞进行的流式细胞术研究表明，该化合物在长时间内有效抑制了细胞增殖；HL-60细胞表现出持续48小时的G1期停滞，而在Jurkat细胞中检测到积累的G0/G1亚群，作为细胞凋亡的指标。对用SCY处理的细胞的进一步分析观察到，HL-60和Jurkat细胞系中Rb蛋白水平降低，p21表达增加。观察到凋亡标记物如磷脂酰丝氨酸外化，还检测到以线粒体膜电位耗散为特征的线粒体功能障碍。SCY激活了线粒体凋亡途径，诱导细胞色素c释放以及随后的caspase-9、-3和-7激活。最后，在用SCY处理后的两种白血病细胞系中均鉴定出凋亡的典型标记物PARP裂解。这些发现表明，SCY通过激活线粒体途径诱导白血病细胞凋亡，突出了其作为未来抗癌药物开发的潜力。
