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Int. J. Mol. Sci. 2010, 11(12), 5323-5338; doi:10.3390/ijms11125323
Article

Antiproliferative Effects of Cucurbitacin B in Breast Cancer Cells: Down-Regulation of the c-Myc/hTERT/Telomerase Pathway and Obstruction of the Cell Cycle

1
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1
,
2
,
3
,
4
 and
1,*
1 Faculty of Medical Technology, Mahidol University Main Campus, 999 Puttamonthon 4 street, Salaya, Nakornpathom 73170, Thailand 2 Faculty of Pharmacy, Mahidol University, Bangkok, Thailand 3 Faculty of Science, Ramkhamhaeng University, Bangkok, Thailand 4 Institute of Molecular Biosciences, Mahidol University, Bangkok, Thailand
* Author to whom correspondence should be addressed.
Received: 19 November 2010 / Revised: 20 December 2010 / Accepted: 21 December 2010 / Published: 22 December 2010
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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: cucurbitacin B; telomerase; hTERT; c-Myc; breast cancer; estrogen receptor cucurbitacin B; telomerase; hTERT; c-Myc; breast cancer; estrogen receptor
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Duangmano, S.; Dakeng, S.; Jiratchariyakul, W.; Suksamrarn, A.; Smith, D.R.; Patmasiriwat, P. 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, 5323-5338.

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