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
相关论文
共 39 条
[1]   Telomeres, telomerase, and telomerase inhibition: Clinical implications for cancer [J].
Ahmed, A ;
Tollefsbol, T .
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 2003, 51 (01) :116-122
[2]   Telomerase in breast cancer [J].
Baykal, A ;
Rosen, D ;
Zhou, CY ;
Liu, JS ;
Sahin, AA .
ADVANCES IN ANATOMIC PATHOLOGY, 2004, 11 (05) :262-268
[3]   Telomerase activity and prognosis in primary breast cancers [J].
Carey, LA ;
Kim, NW ;
Goodman, S ;
Marks, J ;
Henderson, G ;
Umbricht, CB ;
Dome, JS ;
Dooley, W ;
Amshey, SR ;
Sukumar, S .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (10) :3075-3081
[4]   Telomeres, telomerase, and myc.: An update [J].
Cerni, C .
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2000, 462 (01) :31-47
[5]   Inhibitory effects of costunolide on the telomerase activity in human breast carcinoma cells [J].
Choi, SH ;
Im, E ;
Kang, HK ;
Lee, JH ;
Kwak, HS ;
Bae, YT ;
Park, HJ ;
Kim, ND .
CANCER LETTERS, 2005, 227 (02) :153-162
[6]   TRANSCRIPTIONAL REGULATION BY MAP KINASES [J].
DAVIS, RJ .
MOLECULAR REPRODUCTION AND DEVELOPMENT, 1995, 42 (04) :459-467
[7]   Telomeres, telomerase and cancer: an up-date [J].
Dhaene, K ;
Van Marck, E ;
Parwaresch, R .
VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY, 2000, 437 (01) :1-16
[8]   Telomerase: regulation, function and transformation [J].
Dong, CK ;
Masutomi, K ;
Hahn, WC .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2005, 54 (02) :85-93
[9]  
DUBIK D, 1988, J BIOL CHEM, V263, P12705
[10]  
FARNSWORTH NR, 1985, B WORLD HEALTH ORGAN, V63, P965