Antiproliferative effects of cucurbitacin B in breast cancer cells: down-regulation of the c-Myc/hTERT/telomerase pathway and obstruction of the cell cycle

Int J Mol Sci. 2010;11(12):5323-38. doi: 10.3390/ijms11125323. Epub 2010 Dec 22.

Abstract

Naturally occurring cucurbitacins have been shown to have anticancer, antimicrobial and anti-inflammatory activities. In this study, we determined the effects of cucurbitacin B extracted from the Thai herb Trichosanthes cucumerina L. on telomerase regulation in three human breast cancer cell lines (T47D, SKBR-3, and MCF-7) and a mammary epithelium cell line (HBL-100). Cell viability after treatment with cucurbitacin B, which is an active ingredient of this herb, was assessed. Telomeric Repeat Amplification Protocol (TRAP) assays and RT-PCR (qualitative and realtime) were performed to investigate activity of telomerase as well as expression of human telomerase reverse transcriptase (hTERT) and c-Myc. The c-Myc protein level was also determined in SKBR-3 and HBL-100 cells. Our results show that the cucurbitacin B inhibits growth and telomerase activity in the three breast cancer cell lines and exerts an obvious inhibitory effect in the estrogen receptor (ER)-negative breast cancer SKBR-3 cells. The expression of hTERT and c-Myc were also inhibited by cucurbitacin B, In addition, a clear reduction of c-Myc protein was observed after treatment in SKBR-3 cells even with a concentration of cucurbitacin B that was ten-times lower compared to the concentration used for HBL-100. Our findings imply that cucurbitacin B exerts an anticancer effect by inhibiting telomerase via down regulating both the hTERT and c-Myc expression in breast cancer cells.

Keywords: breast cancer; c-Myc; cucurbitacin B; estrogen receptor; hTERT; telomerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Proto-Oncogene Proteins c-myc / biosynthesis*
  • Telomerase / biosynthesis*
  • Trichosanthes / chemistry
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Triterpenes
  • cucurbitacin B
  • TERT protein, human
  • Telomerase