The Mangrove-Derived Diterpenoid Diaporthe B Inhibits the Stemness and Increases the Efficacy of Docetaxel in Prostate Cancer PC-3 Cells

Author:

Xu Yao1,Zhong Zhiwei1,Gao Yiwen1,Wang Yuhui1,Zhang Lanyue1,Huang Huarong1,Zheng Junxia1,Zhang Kun12,Zheng Xi3ORCID,Goodin Susan4

Affiliation:

1. School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, People’s Republic of China

2. School of Biotechnology and Health Sciences, Wuyi University, Jiangmen City, People’s Republic of China

3. Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

4. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

Abstract

The absolute configuration of diaporthe B, a pimarane diterpene isolated from the mangrove derived endophytic fungus Eutypella sp #3E, was determined by a single-crystal x-ray diffraction study. The present study aimed to investigate the effects of diaporthe B on docetaxel-resistant prostate cancer PC-3 cells. Results of our studies showed that docetaxel-resistant PC-3 cells had higher sphere-forming efficiency and an increase in adherence to collagen-coated culture plates. The protein levels of cancer stem cell (CSC)-related markers CD44, CD133, and ALDH1A1 were higher in the docetaxel-resistant PC-3 cells than in the parental cells. Treatment with diaporthe B dose-dependently inhibited the growth and induced apoptosis in the resistant cells. Moreover, diaporthe B treatment decreased the sphere-forming efficiency and the adherence to collagen-coated plates in docetaxel-resistant PC-3 cells. Diaporthe B also decreased the protein levels of CSC-related markers CD44, CD133, and ALDH1A1 in the resistant cells. In addition, a combination of diaporthe B and docetaxel had a more potent effect on growth inhibition and apoptosis in the resistant cells than either agent alone. Our studies suggest that diaporthe B inhibits the stemness of prostate cancer cells and may have therapeutic potential for enhancing the efficacy of docetaxel in docetaxel-resistant prostate cancer cells.

Funder

Natural Science Foundation of China

Jiangmen Program Innovative Research

Department of Education of Guangdong Province

Publisher

SAGE Publications

Subject

Complementary and alternative medicine,Plant Science,Drug Discovery,Pharmacology,General Medicine

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