Mar. Drugs 2013, 11(11), 4570-4584; doi:10.3390/md11114570
Article

Ophiobolin-O Reverses Adriamycin Resistance via Cell Cycle Arrest and Apoptosis Sensitization in Adriamycin-Resistant Human Breast Carcinoma (MCF-7/ADR) Cells

1,†email, 1,†email, 2email, 3email, 1email, 1email, 3email, 2,* email and 1,* email
Received: 30 August 2013; in revised form: 20 October 2013 / Accepted: 24 October 2013 / Published: 14 November 2013
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Multidrug-resistance is a major obstacle facing cancer chemotherapy. This paper demonstrates that novel compound Ophiobolin-O reverses MCF-7/ADR resistance to adriamycin (ADM). The IC50 of ADM treated MCF-7 cells was 2.02 ± 0.05 µM and 74.00 ± 0.18 µM treated MCF-7/ADR cells, about 37-fold, compared to the former. However, 0.1 µM Ophiobolin-O (less than 20% inhibition concentration) combined with ADM caused the decreased IC50 of ADM to 6.67 ± 0.98 µM, indicating it reversed ADM resistance of MCF-7/ADR cells (11-fold). Furthermore, Ophiobolin-O increased ADM-induced mitochondrial pathway apoptosis and G2/M phase arrest, which is partly due to the elevation level of ROS in MCF-7/ADR cells. As we described in this paper, the reversal effect of Ophiobolin-O may be due to the reduction of resistance-related protein P-Glycoprotein (P-gp, also known as MDR1) through inhibiting the activity of the multidrug resistance 1 (MDR1) gene promoter, which makes MCF-7/ADR cells more sensitive to ADM treatment. Assays in nude mice also showed that the combination of ADM and Ophiobolin-O significantly improved the effect of ADM.
Keywords: Ophiobolin-O; adriamycin (ADM); drug resistance reversal
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MDPI and ACS Style

Sun, W.; Lv, C.; Zhu, T.; Yang, X.; Wei, S.; Sun, J.; Hong, K.; Zhu, W.; Huang, C. Ophiobolin-O Reverses Adriamycin Resistance via Cell Cycle Arrest and Apoptosis Sensitization in Adriamycin-Resistant Human Breast Carcinoma (MCF-7/ADR) Cells. Mar. Drugs 2013, 11, 4570-4584.

AMA Style

Sun W, Lv C, Zhu T, Yang X, Wei S, Sun J, Hong K, Zhu W, Huang C. Ophiobolin-O Reverses Adriamycin Resistance via Cell Cycle Arrest and Apoptosis Sensitization in Adriamycin-Resistant Human Breast Carcinoma (MCF-7/ADR) Cells. Marine Drugs. 2013; 11(11):4570-4584.

Chicago/Turabian Style

Sun, Wenxia; Lv, Cuiting; Zhu, Tonghan; Yang, Xue; Wei, Shanjian; Sun, Jieyin; Hong, Kui; Zhu, Weiming; Huang, Caiguo. 2013. "Ophiobolin-O Reverses Adriamycin Resistance via Cell Cycle Arrest and Apoptosis Sensitization in Adriamycin-Resistant Human Breast Carcinoma (MCF-7/ADR) Cells." Mar. Drugs 11, no. 11: 4570-4584.


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