Synergistic Anti-Cancer Activity by the Combination of TRAIL/APO-2L and Celastrol

Hong ZhuInstitute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China, Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University, Shanghai, 200062 China

Wan-Jing DingInstitute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China, Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University, Shanghai, 200062 China

Rui WuInstitute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China, Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University, Shanghai, 200062 China

Qin-Jie WengInstitute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China, Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University, Shanghai, 200062 China

Jian-Shu LouInstitute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China, Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University, Shanghai, 200062 China

Rong-Jia JinInstitute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China, Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University, Shanghai, 200062 China

Wei LuInstitute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China, Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University, Shanghai, 200062 China

Bo YangInstitute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China, Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University, Shanghai, 200062 ChinaCorrespondence[email protected] [email protected]

Qiao-Jun HeInstitute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China, Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University, Shanghai, 200062 ChinaCorrespondence[email protected] [email protected]

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ABSTRACT

The present study demonstrates that the combination of TRAIL/APO-2L and celastrol exerts strong synergistic antiproliferative effect against human cancer cells including ovary cancer OVCAR-8, colon cancer SW620, and lung cancer 95-D, with the combination indices below 0.8. Moreover, the in vivo antitumor efficacy of TRAIL/APO-2L was dramatically increased by celastrol. These enhanced anticancer activities were accompanied by the prompt onset of caspase-mediated apoptosis. Taken together, our data firstly demonstrate the synergistic anticancer capabilities achieved by combining TRAIL/APO-2L and celastrol, and moreover, open new opportunities to enhance the effectiveness of future treatment regimens using TRAIL/APO-2L.

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Synergistic Anti-Cancer Activity by the Combination of TRAIL/APO-2L and Celastrol

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Synergistic Anti-Cancer Activity by the Combination of TRAIL/APO-2L and Celastrol

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