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Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells
Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, Yinchuan 750021, Ningxia, China
College of Life Science, Ningxia University, Yinchuan 750021, Ningxia, China
* Author to whom correspondence should be addressed.
Received: 25 September 2012; in revised form: 16 November 2012 / Accepted: 30 November 2012 / Published: 4 December 2012
Abstract: In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC50) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC50 values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs.
Keywords: azithromycin; macrolides; vincristine; cytotoxicity; apoptosis; cancer cells
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MDPI and ACS Style
Zhou, X.; Zhang, Y.; Li, Y.; Hao, X.; Liu, X.; Wang, Y. Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells. Cancers 2012, 4, 1318-1332.
Zhou X, Zhang Y, Li Y, Hao X, Liu X, Wang Y. Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells. Cancers. 2012; 4(4):1318-1332.
Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming; Wang, Yujiong. 2012. "Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells." Cancers 4, no. 4: 1318-1332.