South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Science, CARMA: Centre for Cardio-Metabolic Research in Africa, Stellenbosch University, Cape Town, 8000, South Africa.
BMC Complement Med Ther. 2024 Sep 10;24(1):332. doi: 10.1186/s12906-024-04615-x.
Triple-negative breast cancer (TNBC) represents a significant global health crisis due to its resistance to conventional therapies and lack of specific molecular targets. This study explored the potential of Eriocephalus racemosus (E. racemosus) as an alternative treatment for TNBC. The cytotoxic properties and high-resolution respirometry mitochondrial activities of E. racemosus against the MDA-MB 231 TNBC cell line were evaluated.
Hexane solvent and bioactive fraction extractions of E. racemosus were performed, while mass spectrometry-based metabolite profiling was used to identify the phytochemical constituents of the extracts. The extracts were further tested against MDA-MB 231 TNBC cells to determine their cytotoxicity. The mode of cell death was determined using flow cytometry. The activities of caspases 3, 8, and 9 were assessed using a multiplex activity assay kit. Glycolytic activity and High-resolution respirometry measurements of mitochondrial function in the MDA-MB 231 cell line were conducted using the Seahorse XFp and Oroboros O2K.
Metabolite profiling of E. racemosus plant crude extracts identified the presence of coumarins, flavonoids, sesquiterpenoids, triterpenoids, and unknown compounds. The extracts demonstrated promising cytotoxic activities, with a half maximal inhibitory concentration (IC) of 12.84 µg/mL for the crude hexane extract and 15.49 µg/mL for the bioactive fraction. Further, the crude hexane and bioactive fraction extracts induced apoptosis in the MDA-MB-231 TNBC cells, like the reference drug cisplatin (17.44%, 17.26% and 20.25%, respectively) compared to untreated cells. Caspase 3 activities confirmed the induction of apoptosis in both cisplatin and the plant crude extracts, while caspase 8 and 9 activities confirmed the activation of both the intrinsic and extrinsic apoptosis pathways. Increased levels of glycolytic activity were observed in the hexane crude extract. High-resolution respiratory measurements showed elevated mitochondrial activities in all mitochondrial states except for complex-IV activity.
These findings support further exploration of E. racemosus as a potential therapeutic agent for TNBC, offering a promising avenue for the development of targeted treatments with minimal adverse effects.
三阴性乳腺癌（TNBC）因其对常规疗法的抵抗力和缺乏特定分子靶标而成为一个重大的全球健康危机。本研究探讨了 Eriocephalus racemosus（E. racemosus）作为 TNBC 替代治疗的潜力。评估了 E. racemosus 对 MDA-MB 231 TNBC 细胞系的细胞毒性特性和高分辨率呼吸仪线粒体活性。
对 E. racemosus 进行了己烷溶剂和生物活性部分提取，同时基于质谱的代谢物分析用于鉴定提取物中的植物化学成分。进一步测试提取物对 MDA-MB 231 TNBC 细胞的细胞毒性。使用流式细胞术确定细胞死亡方式。使用多活性测定试剂盒评估半胱天冬酶 3、8 和 9 的活性。使用 Seahorse XFp 和 Oroboros O2K 对 MDA-MB 231 细胞系的糖酵解活性和高分辨率呼吸仪线粒体功能进行测量。
E. racemosus 植物粗提物的代谢物分析确定了香豆素、类黄酮、倍半萜、三萜和未知化合物的存在。提取物表现出有希望的细胞毒性活性，己烷粗提取物的半最大抑制浓度（IC）为 12.84µg/mL，生物活性部分为 15.49µg/mL。此外，与未处理的细胞相比，己烷粗提物和生物活性部分提取物在 MDA-MB-231 TNBC 细胞中诱导了细胞凋亡，就像参考药物顺铂（分别为 17.44%、17.26%和 20.25%）一样。半胱天冬酶 3 活性证实了顺铂和植物粗提取物诱导的细胞凋亡，而半胱天冬酶 8 和 9 活性证实了内在和外在凋亡途径的激活。己烷粗提物中观察到糖酵解活性增加。高分辨率呼吸测量显示除了复合物 IV 活性外，所有线粒体状态的线粒体活性均升高。
这些发现支持进一步探索 E. racemosus 作为 TNBC 的潜在治疗剂，为开发具有最小不良反应的靶向治疗提供了有希望的途径。
