Damnacanthal is a potent inducer of apoptosis with anticancer activity by stimulating p53 and p21 genes in MCF-7 breast cancer cells

被引:38
作者
Aziz, Muhammad Yusran Abdul [1 ]
Omar, Abdul Rahman [2 ]
Subramani, Tamilselvan [1 ]
Yeap, Swee Keong [2 ]
Ho, Wan Yong [1 ]
Ismail, Nor Hadiani [3 ]
Ahmad, Syahida [4 ]
Alitheen, Noorjahan Banu [1 ]
机构
[1] Univ Putra Malaysia, Fac Biotechnol & Biomol Sci, Dept Cell & Mol Biol, Serdang 43400, Selangor, Malaysia
[2] Univ Putra Malaysia, Inst Biosci, Serdang 43400, Selangor, Malaysia
[3] Univ Teknol Mara, Fac Sci Appl, Shah Alam 40450, Selangor, Malaysia
[4] Univ Putra Malaysia, Fac Biotechnol & Biomol Sci, Dept Biochem, Serdang 43400, Selangor, Malaysia
关键词
damnacanthal; MCF-7; anticancer; caspase; p53; p21; apoptosis; MORINDA-CITRIFOLIA; ANTHRAQUINONES; CURCUMIN;
D O I
10.3892/ol.2014.1898
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases, including cancer. Although noni has long been consumed in Asian and Polynesian countries, the molecular mechanisms by which it exerts several benefits are starting to emerge. In the present study, the effect of damnacanthal on MCF-7 cell growth regulation was investigated. Treatment of MCF-7 cells with damnacanthal for 72 h indicated an antiproliferative activity. The MTT method confirmed that damnacanthal inhibited the growth of MCF-7 cells at the concentration of 8.2 mu g/ml for 72 h. In addition, the drug was found to induce cell cycle arrest at the G1 checkpoint in MCF-7 cells by cell cycle analysis. Damnacanthal induced apoptosis, determined by Annexin V-fluorescein isothiocyanate/propidium iodide (PI) dual-labeling, acridine-orange/PI dyeing and caspase-7 expression. Furthermore, damnacanthal-mediated apoptosis involves the sustained activation of p21, leading to the transcription of p53 and the Bax gene. Overall, the present study provided significant evidence demonstrating that p53-mediated damnacanthal induced apoptosis through the activation of p21 and caspase-7.
引用
收藏
页码:1479 / 1484
页数:6
相关论文
共 25 条
  • [1] Ali AM, 2000, PHARM BIOL, V38, P298, DOI 10.1076/1388-0209(200009)38:4
  • [2] 1-A
  • [3] FT298
  • [4] Alitheen NB, 2010, INT FOOD RES J, V17, P711
  • [5] DiSalvo J, 1997, P SOC EXP BIOL MED, V214, P285
  • [6] WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION
    ELDEIRY, WS
    TOKINO, T
    VELCULESCU, VE
    LEVY, DB
    PARSONS, R
    TRENT, JM
    LIN, D
    MERCER, WE
    KINZLER, KW
    VOGELSTEIN, B
    [J]. CELL, 1993, 75 (04) : 817 - 825
  • [7] Promoting apoptosis as a strategy for cancer drug discovery
    Fesik, SW
    [J]. NATURE REVIEWS CANCER, 2005, 5 (11) : 876 - 885
  • [8] Targeting apoptosis pathways in cancer therapy
    Ghobrial, IM
    Witzig, TE
    Adjei, AA
    [J]. CA-A CANCER JOURNAL FOR CLINICIANS, 2005, 55 (03) : 178 - 194
  • [9] Mitochondria and apoptosis
    Green, DR
    Reed, JC
    [J]. SCIENCE, 1998, 281 (5381) : 1309 - 1312
  • [10] Curcumin: From ancient medicine to current clinical trials
    Hatcher, H.
    Planalp, R.
    Cho, J.
    Tortia, F. M.
    Torti, S. V.
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2008, 65 (11) : 1631 - 1652