Inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cells

Abstract

Roburic acid (ROB) is a naturally occurred tetracyclic triterpenoid, and the anticancer activity of this compound has not been reported. Docetaxel (DOC) is the first-line chemotherapeutic agent for advanced stage prostate cancer but toxic side effects and drug resistance limit its clinical success. In this study, the potential synergistic anticancer effect and the underlying mechanisms of ROB in combination with DOC on prostate cancer were investigated. The results showed that ROB and DOC in combination synergistically inhibited the growth of prostate cancer cells. The combination also strongly induced apoptosis, and suppressed cell migration, invasion and sphere formation. Mechanistic study showed that the combined effects of ROB and DOC on prostate cancer cells were associated with inhibition of NF-κB activation, down regulation of Bcl-2 and up regulation of Bax. Knockdown of NF-κB by small interfering RNA (siRNA) significantly decreased the combined effect of ROB and DOC. Moreover, we found that esomeprazole (ESOM), a proton pump inhibitor (PPI), strongly enhanced the effectiveness of ROB and DOC on prostate cancer cells in acidic culture medium. Since acidic micro environment is known to impair the efficacy of current anticancer therapies, ESOM combined with ROB and DOC may be an effective approach for improving the treatment of prostate cancer patients.

Graphical abstract

Keywords:

• Prostate cancer
• roburic acid
• docetaxel
• combination

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The present study was supported by grants from the Department of Education of Guangdong Province [2017KZDXM084, 2017KSYS010, 2019KZDZX2003, and 2019KZDXM035], the Jiangmen Program for Innovative Research Team [No: 2017TD02], and the Department of Science and Technology of Jiangmen [No: 2016350100170008351, 2018110100330005446]. Dr. Xi Zheng is the Unilever Chair in Nutrition and Disease Prevention Research at Rutgers University.