The novel resveratrol analog HS-1793-induced polyploid LNCaP prostate cancer cells are vulnerable to downregulation of Bcl-xL.

Abstract

Since resveratrol is not a potent cytotoxic compound when compared with other chemotherapeutic agents, several previous studies have been performed to obtain synthetic analogs of resveratrol with potent activity. Our previous study demonstrated that the resveratrol analog HS-1793 showed stronger antitumor activity than resveratrol in various cancer cells. We examined the antitumor activity exerted by HS-1793 in prostate cancer cells, and we observed that HS-1793 acts as a polyploidy inducer. Noticeably, multinucleation and polyploidization were induced in most LNCaP cells treated with HS-1793 at the dose causing a slight decline in cell viability. However, the induction of multinucleation and polyploidization was much lower in PC-3 prostate cancer cells treated with the same dose of HS-1793. Western blot and RT-PCR analyses showed that the expression of Aurora B was almost undetectable in LNCaP cells, but it was highly expressed in PC-3 cells. Further, silencing of Aurora B sensitized PC-3 cells to HS-1793-induced multi-nucleation. These results indicate that expression of Aurora B determines multinucleation in prostate cancer cells treated with HS-1793. Additional assays using multiple cancer cell lines show that the population of multinucleated cells induced by HS-1793 treatment is inversely proportional to Aurora B expression. We further elicited that the HS-1793-induced polyploid LNCaP cells are vulnerable to downregulation of Bcl-xL. Since the polyploidization in LNCaP induced by HS-1793 does not appear to cause definite commitment to apoptosis, the termination of polyploid cells by inhibition of Bcl-xL could provide an advantageous means to improve chemotherapeutic efficacy of HS-1793.

• Authors: Na Young Jeong, Young Geol Yoon, Jee Hyun Rho, Jee Suk Lee, Sang Yeob Lee, Ki Soo Yoo, Suhee Song, Hongsuk Suh, Yung Hyun Choi, Young Hyun Yoo
• Journal: International journal of oncology (Int J Oncol) Vol. 38 Issue 6 Pg. 1597-604 (Jun 2011) ISSN: 1791-2423 [Electronic] Greece
• PMID: 21424121 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-(6-hydroxy-2-naphthyl)-1,3-benzenediol
• Antineoplastic Agents
• BCL2L1 protein, human
• Naphthols
• Resorcinols
• bcl-X Protein
• AURKB protein, human
• Aurora Kinase B
• Aurora Kinases
• Protein Serine-Threonine Kinases

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Aurora Kinase B
• Aurora Kinases
• Cell Line, Tumor
• Cell Survival (drug effects)
• Down-Regulation (drug effects)
• Drug Synergism
• HCT116 Cells
• Humans
• K562 Cells
• Male
• Naphthols (pharmacology)
• Polyploidy
• Prostatic Neoplasms
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Resorcinols (pharmacology)
• U937 Cells
• bcl-X Protein (antagonists & inhibitors, metabolism)