Abstract

Abstract 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 Thai herb Trichosanthes cucumerina L. on the regulation of telomerase 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 by MTT assay and cell cycle analysis by flow cytometry. 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. Our results show that the cucurbitacin B inhibits growth and telomerase activity in the three breast cancer cell lines and an obvious inhibitory effect was seen in the estrogen receptor (ER)-negative breast cancer cell SKBR-3 rather than ER-positive MCF-7 and T47D cells. The expressions of hTERT and c-Myc were also inhibited by cucurbitacin B, In addition, the reduction of c-Myc protein after the treatment was clearly observed in SKBR-3 cells even at the ten times lower concentration of cucurbitacin B compared to the concentration used for the HBL-100. DNA flow cytometric analysis indicated that treatment with cucurbitacin B resulted in G2/M arrest. These results imply that cucurbitacin B exerts anticancer effect by inhibiting telomerase via down regulating both the hTERT and c-Myc expression and arrest of the cell cycle at G2/M phase in breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4235. doi:10.1158/1538-7445.AM2011-4235

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