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Mar. Drugs 2013, 11(11), 4570-4584;

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

Department of Biochemistry and Molecular Biology, College of Basic Medical, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China
The Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Received: 30 August 2013 / Revised: 20 October 2013 / Accepted: 24 October 2013 / Published: 14 November 2013
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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. View Full-Text
Keywords: Ophiobolin-O; adriamycin (ADM); drug resistance reversal Ophiobolin-O; adriamycin (ADM); drug resistance reversal

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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.

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