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姜黄素-半乳甘露聚糖复合物抑制人宫颈癌细胞增殖:可能通过细胞周期阻滞和细胞凋亡实现。

Curcumin-Galactomannoside Complex inhibits the Proliferation of Human Cervical Cancer Cells: Possible Role in Cell Cycle Arrest and Apoptosis.

机构信息

Department of Biochemistry, St. Thomas College, Pala, Kottayam, Kerala, India.

R & D Center, Akay Natural Ingredients Pvt.Ltd, Cochin, India.

出版信息

Asian Pac J Cancer Prev. 2021 Jun 1;22(6):1713-1720. doi: 10.31557/APJCP.2021.22.6.1713.

Abstract

BACKGROUND

Cervical cancer is the most common cancer and has the highest morbidity rate of gynaecological malignancies in women worldwide. So, the development of effective anti-cancer agents to treat this condition is vital. Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade, free-curcuminoids (curcumin-galactomannoside complex; CGM) on cervical cancer cells (HeLa) of human origin. In this study, we examined the anticancer potential of CGM as well as its effects on the cell cycle and the apoptosis of HeLa cancer cell.

METHODS

Determination of anti-proliferative and apoptosis validation of CGM on HeLa cells was performed by 3-(4,5-Dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT), acridine orange/propidium iodide and annexin-V-fluorescein isothiocyanate assays. Measurement of Reactive Oxygen Species (ROS) production, Caspase activities and protein expression experiments were performed to investigate the potential mechanisms of action in the apoptotic process.

RESULTS

The cytotoxic assays revealed that the CGM showed inhibition of cell survival and exhibited high cytotoxic activity against HeLa cells at 25 μg/mL. Further studies on morphological changes were done in CGM-treated cervical cancer cells contributing to apoptosis. Flow cytometry analysis with Annexin V-FITC and PI staining precisely indicated that CGM induced apoptosis in HeLa cell lines at 25 μg/mL. By the supplementation of CGM showed an increase in Bax and cleaved caspase-8 protein in HeLa cells after 48 h exposure.

CONCLUSION

The evidence obtained from this study suggests that CGM is a potent and promising natural formulation against cervical cancer cells via induction of apoptosis through ROS mediated mitochondrial damage in HeLa cells. Hence, CGM could be further explored as a potential lead in treating cancer.
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摘要

背景

宫颈癌是全球女性中最常见的癌症,也是妇科恶性肿瘤中发病率最高的癌症。因此,开发有效的抗癌药物来治疗这种疾病至关重要。考虑到人们最近对游离(未结合)姜黄素类的兴趣,本研究探讨了新型食品级游离姜黄素(姜黄素-半乳甘露聚糖复合物;CGM)对人源宫颈癌(HeLa)细胞的疗效。在这项研究中,我们研究了 CGM 的抗癌潜力及其对 HeLa 癌细胞周期和细胞凋亡的影响。
方法:通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)、吖啶橙/碘化丙啶和 Annexin-V-荧光素异硫氰酸酯测定法,测定 CGM 对 HeLa 细胞的抗增殖和凋亡验证。为了研究凋亡过程中的潜在作用机制,进行了活性氧(ROS)产生、半胱天冬酶活性和蛋白质表达实验的测量。
结果:细胞毒性测定表明,CGM 抑制细胞存活,并在 25 μg/mL 时对 HeLa 细胞表现出高细胞毒性活性。在 CGM 处理的宫颈癌细胞中进行的形态变化进一步研究有助于细胞凋亡。用 Annexin V-FITC 和 PI 染色的流式细胞术分析精确地表明,CGM 在 25 μg/mL 时诱导 HeLa 细胞系凋亡。通过补充 CGM,在 HeLa 细胞中观察到 Bax 和裂解的半胱天冬酶-8 蛋白增加,在 48 小时暴露后。
结论:从这项研究中获得的证据表明,CGM 通过诱导 HeLa 细胞中 ROS 介导的线粒体损伤导致细胞凋亡,是一种针对宫颈癌细胞的有效且有前途的天然制剂。因此,CGM 可以进一步探索作为治疗癌症的潜在先导药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc9/8418838/3e3115dfa83f/APJCP-22-1713-g001.jpg

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