A new chalcone derivative (E)-3-(4-methoxyphenyl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one suppresses prostate cancer involving p53-mediated cell cycle arrests and apoptosis.

Abstract

Previous studies suggested chalcones as antineoplastic drug candidates. We synthesized a new chalcone derivative (E)-3-(4-methoxyphenyl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one, (CHO27) with an up to 1000-fold increased cytotoxic potency relative to its parent compound in cell culture assays. CHO27 at low nanomolar levels, inhibited prostate cancer (PCa) cell growth through cell cycle arrest and caspase-dependent apoptosis. Activation of p53 accounted for, at least in part, the growth inhibition by CHO27 in vitro. Furthermore, i.p. administration of CHO27 suppressed the growth of established PCa 22Rv1 xenograft tumors accompanied with p53 and p21(Cip1) induction. CHO27 may be a lead for development of new therapeutic agents for PCa.

• Authors: Yong Zhang, Balasubramanian Srinivasan, Chengguo Xing, Junxuan Lü
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 9 Pg. 3689-98 (Sep 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22993307 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Chalcones
• TP53 protein, human
• Tumor Suppressor Protein p53

Topics

• Animals
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Growth Processes (drug effects)
• Cell Line, Tumor
• Chalcones (pharmacology)
• Dose-Response Relationship, Drug
• HCT116 Cells
• Humans
• Male
• Mice
• Mice, Nude
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Random Allocation
• Tumor Suppressor Protein p53 (metabolism)
• Xenograft Model Antitumor Assays