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

2021 ◽  
Vol 16 (12) ◽  
pp. 1934578X2110496
Author(s):  
Yao Xu ◽  
Zhiwei Zhong ◽  
Yiwen Gao ◽  
Yuhui Wang ◽  
Lanyue Zhang ◽  
...  

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.

Author(s):  
Suleyman Ilhan ◽  
Gamze Dilekci ◽  
Adem Guner ◽  
Hakan Bektas

Background: Investigating the effects of newly synthesized agents on various molecular mechanisms to understand their mechanism of action is an important step of pre-clinical screening. Benzimidazoles are composed of a unique fused benzene and imidazole ring and have attracted great attention due to their broad bioactivities, including antitumor. Objective: In the current study, we reported the synthesis of novel benzimidazole derivatives and investigated the possible cytotoxic and anti-angiogenic effects on human prostate cancer and umbilical vein endothelial cells (HUVECs). Methods: MTT assay was used to assess cell viability. A scratch assay was conducted to monitor the migration of cells. mRNA expression levels of VEGF, MMP-2, and MMP-9 were evaluated using qPCR. Changes in protein levels were evaluated by western blotting. Results: Compound G1, having a chlorine moiety, showed a potent cytotoxic activity on both prostate cancer cells and HUVECs, and inhibited cell migration via decreasing the mRNA and protein levels of key angiogenesis-related molecules such as VEGF, MMP-2, and MMP-9. Conclusion: These results suggest that newly synthesized G1 may be a novel anti-angiogenic agent for prostate cancer treatment.


The Prostate ◽  
2010 ◽  
Vol 71 (2) ◽  
pp. 111-124 ◽  
Author(s):  
Sandra Cuffe ◽  
Catherine M. Dowling ◽  
James Claffey ◽  
Clara Pampillón ◽  
Megan Hogan ◽  
...  

Oncotarget ◽  
2017 ◽  
Vol 9 (13) ◽  
pp. 10962-10977 ◽  
Author(s):  
David W. McIlwain ◽  
Melissa L. Fishel ◽  
Alexander Boos ◽  
Mark R. Kelley ◽  
Travis J. Jerde

2008 ◽  
Vol 314 (17) ◽  
pp. 3162-3174 ◽  
Author(s):  
N PAPADOPOULOU ◽  
I CHARALAMPOPOULOS ◽  
K ALEVIZOPOULOS ◽  
A GRAVANIS ◽  
C STOURNARAS

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