Department of Life Sciences, National Chung Hsing University, Taichung.
Department of Physiology, National Yang Ming Chiao Tung University, Taipei.
Integr Cancer Ther. 2021 Jan-Dec;20:15347354211002662. doi: 10.1177/15347354211002662.
Cardiac glycosides (CGs) possess a chemical structure similar to steroids, and are inhibitors of the sodium potassium pump. An anti-tumor effect of CGs in breast and prostate cancers has been reported, but the effect of CGs on ovarian cancer is still unclear.
In this study, the effects of CGs on proliferation, cytotoxicity and cell cycle of ovarian cancer cell line (SKOV-3) have been investigated.
The cell proliferation and cytotoxicity were detected by MTT assay and LDH activity assay, respectively. CGs, at concentrations higher than IC50, decreased cell proliferation and showed increased cytotoxicity toward SKOV-3 cells. The colony-formation ability was reduced after treatment with digoxin and digitoxin for 10 days. Furthermore, we explored the effect of digoxin and digitoxin on the distribution of cell cycle by flow cytometry.
Results revealed that both digoxin and digitoxin led to cell cycle arrest in G/G phase with 24 or 48 hours, but the arrest of G/G phase was not observed at 72 hours. We evaluated the percentage of hypodiploid cell population as an index of the cellular fragments through flow cytometry. The data indicated that cellular fragments were significantly increased by treating with digitoxin at the concentrations of IC50 and 10 M for 72 hours.
Taken together, these data suggest that CGs decreased cell proliferation and increased cytotoxicity through cell cycle arrest at the G/G phase. CGs have anti-tumor effect in SKOV-3 cells and might be a potential therapeutic drug for ovarian cancer. Since this study is a preliminary investigation of CGs on SKOV-3 cells, more experiments might be performed in the future. Furthermore, more ovarian cancer cell lines might also be employed in the future studies to confirm the effect of CGs in ovarian cancer.
强心苷(CGs)具有与类固醇相似的化学结构,是钠钾泵的抑制剂。已报道 CGs 在乳腺癌和前列腺癌中有抗肿瘤作用,但 CGs 对卵巢癌的作用尚不清楚。
本研究旨在探讨 CGs 对卵巢癌细胞系(SKOV-3)增殖、细胞毒性和细胞周期的影响。
采用 MTT 法和 LDH 活性法分别检测细胞增殖和细胞毒性。CGs 在高于 IC50 的浓度下,降低细胞增殖,并对 SKOV-3 细胞表现出增加的细胞毒性。地高辛和毛花苷 C 处理 10 天后,集落形成能力降低。此外,我们通过流式细胞术探讨了地高辛和毛花苷 C 对细胞周期分布的影响。
结果表明,地高辛和毛花苷 C 均导致细胞周期阻滞在 G1/G0 期,分别为 24 或 48 小时,但在 72 小时未观察到 G1/G0 期阻滞。我们通过流式细胞术评估低倍体细胞群体的百分比作为细胞碎片的指标。结果表明,毛花苷 C 在 IC50 和 10 μM 浓度下处理 72 小时,细胞碎片明显增加。
综上所述,CGs 通过细胞周期阻滞在 G1/G0 期,降低细胞增殖并增加细胞毒性。CGs 对 SKOV-3 细胞具有抗肿瘤作用,可能是卵巢癌的潜在治疗药物。由于本研究是 CGs 对 SKOV-3 细胞的初步研究,未来可能需要进行更多的实验。此外,未来的研究可能还需要使用更多的卵巢癌细胞系来确认 CGs 在卵巢癌中的作用。