Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, 321 Kuang Fu 2 Road, Hsinchu 30011, Taiwan.
Institute of Molecular Medicine, College of Life Sciences, National Tsing Hua University, 101 Kuang Fu 2 Road, Hsinchu 30013, Taiwan.
Oxid Med Cell Longev. 2020 Jan 25;2020:7353618. doi: 10.1155/2020/7353618. eCollection 2020.
Cisplatin chemotherapy causes myelosuppression and often limits treatment duration and dose escalation in patients. Novel approaches to circumvent or lessen myelotoxicity may improve clinical outcome and quality of life in these patients. (CS) is a freshwater unicellular green alga and exhibits encouraging efficacy in immunomodulation and anticancer in preclinical studies. However, the efficacy of CS on chemoprotection remains unclear. We report here, for the first time, that CS extract (CSE) could protect normal myeloid cells and PBMCs from cisplatin toxicity. Also, cisplatin-induced apoptosis in HL-60 cells was rescued through reservation of mitochondrial function, inhibition of cytochrome c release to cytosol, and suppression of caspase and PARP activation. Intriguingly, cotreatment of CSE attenuated cisplatin-evoked hypocellularity of bone marrow in mice. Furthermore, we observed the enhancement of CSF-GM activity in bone marrow and spleen in mice administered CSE and cisplatin, along with increased CD11b levels in spleen. In conclusion, we uncovered a novel mechanism of CSE on myeloprotection, whereby potentially supports the use of CSE as a chemoprotector against cisplatin-induced bone marrow toxicity. Further clinical investigation of CSE in combination with cisplatin is warranted.
顺铂化疗会导致骨髓抑制,常常限制患者的治疗持续时间和剂量增加。规避或减轻骨髓毒性的新方法可能会改善这些患者的临床结果和生活质量。(CS)是一种淡水单细胞绿藻,在免疫调节和临床前研究中的抗癌方面表现出令人鼓舞的疗效。然而,CS 对化疗保护的疗效尚不清楚。我们在这里首次报告,CS 提取物(CSE)可以保护正常髓样细胞和 PBMC 免受顺铂毒性的影响。此外,通过保留线粒体功能、抑制细胞色素 c 向细胞质释放以及抑制半胱天冬酶和 PARP 激活,CSE 挽救了 HL-60 细胞中的顺铂诱导的细胞凋亡。有趣的是,CSE 共处理减轻了顺铂诱导的小鼠骨髓细胞减少。此外,我们观察到在给予 CSE 和顺铂的小鼠的骨髓和脾脏中 CSF-GM 活性增强,并且脾脏中的 CD11b 水平增加。总之,我们揭示了 CSE 对骨髓保护的新机制,这可能支持将 CSE 用作顺铂诱导的骨髓毒性的化学保护剂。需要进一步的临床研究来评估 CSE 与顺铂的联合应用。