Effects of Fucoidan and Chemotherapeutic Agent Combinations on Malignant and Non-malignant Breast Cell Lines
Effects of Fucoidan and Chemotherapeutic Agent Combinations on Malignant and Non-malignant Breast Cell Lines
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DOI：
10.2174/1389201018666171115115112
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发表时间：
2017-01-01
影响因子：
2.8
通讯作者：
Hiss, Donavon
中科院分区：
文献类型：
--
作者：
Abudabbus, Aisha;Badmus, Jelili A.;Hiss, Donavon
目的：乳腺癌是发达国家和第三世界国家妇女死亡的主要原因。岩藻依聚糖是一种天然植物代谢产物，由褐藻产生，具有抗癌潜力。本研究测定了褐藻糖胶单独和与一线抗癌药物（顺铂、阿霉素和紫杉醇）联合应用对MCF-7乳腺癌细胞和非恶性MCF-12 A乳腺上皮细胞的细胞毒性、凋亡和细胞周期的影响。流式细胞仪检测细胞周期分布和凋亡，Annexin VFITC/PI和Hoechst 33342染色，caspase-3，-7和-9 activation.Results：单独岩藻依聚糖硫酸酯对MCF-7乳腺癌细胞的细胞毒性显著高于MCF-12 A非癌乳腺上皮细胞系。在MCF-7细胞中，岩藻依聚糖的存在导致细胞周期停滞在G1期，细胞积聚在亚G1期，半胱天冬酶-3，7和9被激活。此外，褐藻糖胶与标准化疗药物顺铂，阿霉素和紫杉醇的组合显着增强这些药物的细胞毒性和细胞在G2/M和亚G1期的积累，并诱导凋亡。岩藻聚糖处理和未处理的MCF-12 A细胞的细胞毒性和细胞周期分布方面没有观察到显着差异。相比之下，在非癌MCF-12 A细胞中，岩藻依聚糖通过增加其IC 50值来减弱阿霉素和顺铂联合使用的毒性。这种效果没有表现出与紫杉醇combination.Conclusions：岩藻依聚糖是一种有效的抗肿瘤剂，无论是单独或与顺铂，阿霉素和紫杉醇在MCF-7乳腺癌细胞。区分癌细胞和非癌细胞的药物组合提供了一种合理可行的策略，可以获得治疗效果并避免可能的毒性和副作用。这些研究结果表明，岩藻依聚糖是一个有前途的候选癌症联合治疗。
Objectives: Breast cancer is a leading cause of death among women in both developed and Third World countries. Fucoidan is a natural plant metabolite produced by brown seaweeds with proven anticancer potential. This study determined the cytotoxic, apoptotic and cell cycle effects of fucoidan alone and in combination with first-line anticancer drugs (cisplatin, doxorubicin and taxol) in MCF-7 breast cancer cells and non-malignant MCF-12A breast epithelial cells as control.Methods: Cytotoxicity was evaluated using the MTT reduction assay. Cell cycle distribution and apoptosis were assessed by flow cytometry using Annexin VFITC/PI and Hoechst 33342 staining, and caspases-3, -7 and -9 activation.Results: Fucoidan alone was significantly more cytotoxic to MCF-7 breast cancer cells compared to the MCF-12A non-cancerous breast epithelial cell line. In MCF-7 cells, the presence of fucoidan caused cell cycle arrest at G1 with accumulation of cells in the sub-G1 phase with the activation of caspases-3, -7 and -9. Furthermore, combination of fucoidan with the standard chemotherapeutic agents-cisplatin, doxorubicin and taxol-significantly enhanced the cytotoxicity of these drugs and accumulation of cells in the G2/M and sub-G1 phases, and induction of apoptosis. No significant differences were observed between fucoidan-treated and untreated MCF-12A cells with respect to cytotoxicity and cell cycle distribution profiles. By contrast, in non-cancerous MCF-12A cells, fucoidan attenuated the toxicity of doxorubicin and cisplatin in combination by increasing their IC50 values. This effect was not demonstrated with the taxol combination.Conclusions: Fucoidan is an effective antitumor agent, either alone or in combination with cisplatin, doxorubicin and taxol in MCF-7 breast cancer cells. Drug combinations that discriminate between cancerous and non-cancerous cells afford a plausible and viable strategy of attaining therapeutic efficacy and avoiding possible toxicity and side effects. These findings suggest that fucoidan is a promising candidate for cancer combination therapies.