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

被引:50
作者
Duangmano, Suwit [1 ]
Dakeng, Sumana [1 ]
Jiratchariyakul, Weena [2 ]
Suksamrarn, Apichart [3 ]
Smith, Duncan R. [4 ]
Patmasiriwat, Pimpicha [1 ]
机构
[1] Mahidol Univ, Fac Med Technol, Salaya 73170, Nakornpathom, Thailand
[2] Mahidol Univ, Fac Pharm, Bangkok 10700, Thailand
[3] Ramkhamhang Univ, Fac Sci, Bangkok, Thailand
[4] Mahidol Univ, Inst Mol Biosci, Bangkok 10700, Thailand
关键词
cucurbitacin B; telomerase; hTERT; c-Myc; breast cancer; estrogen receptor; TELOMERASE ACTIVITY; TRANSCRIPTIONAL REGULATION; MYC; INHIBITION; EXPRESSION; APOPTOSIS; TRANSFORMATION; COSTUNOLIDE; ESTROGEN; THERAPY;
D O I
10.3390/ijms11125323
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:5323 / 5338
页数:16
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