The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene Lactone in MCF7 Cells: A Bioassay-Guided Approach

被引:18
作者
Karimian, Hamed [1 ]
Fadaeinasab, Mehran [2 ]
Moghadamtousi, Soheil Zorofchian [2 ]
Hajrezaei, Maryam [1 ]
Zahedifard, Maryam [1 ]
Razavi, Mahboubeh [1 ]
Safi, Sher Zaman [3 ]
Mohan, Syam [4 ]
Khalifa, Shaden A. M. [5 ]
El-Seedi, Hesham R. [5 ,6 ]
Abdulla, Mahmood Amin [7 ]
Ali, Hapipah Mohd [2 ]
Noordin, Mohamad Ibrahim [1 ]
机构
[1] Univ Malaya, Fac Med, Dept Pharm, Kuala Lumpur 50603, Malaysia
[2] Univ Malaya, Fac Sci, Dept Chem, Kuala Lumpur 50603, Malaysia
[3] Univ Malaya, Fac Med, Dept Med, Kuala Lumpur 50603, Malaysia
[4] Jazan Univ, Med Res Ctr, Jazan, Saudi Arabia
[5] Karolinska Univ Hosp, Dept Expt Hematol, Stockholm, Sweden
[6] Uppsala Univ, Dept Med Chem, Div Pharmacognosy, Uppsala, Sweden
[7] Univ Malaya, Fac Med, Dept Biomed Sci, Kuala Lumpur 50603, Malaysia
关键词
Tanacetum polycephalum; Asteraceae; Sesquiterpene lactone; 8; beta-; hydroxyl-4; beta; 15-dihydrozaluzanin C; Breast cancer; Apoptosis; LA7; cells; MCF7; ESSENTIAL OIL; PARTHENOLIDE; CYCLE; DEATH; BCL-2; SENSITIVITY; ANTICANCER; STRATEGIES; HELENALIN; INDUCTION;
D O I
10.1159/000430273
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: Tanacetum polycephalum L. Schultz-Bip is a member of the Asteraceae family. This study evaluated the chemopreventive effect of a T. polycephalum hexane extract (TPHE) using in in vivo and in vitro models. Methods and Results: Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8 beta-hydroxyl-4 beta, 15-dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels. Conclusion: This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis. Copyright (C) 2015 S. Karger AG, Basel
引用
收藏
页码:988 / 1003
页数:16
相关论文
共 51 条
[1]   Thyroid status affects rat liver regeneration after partial hepatectomy by regulating cell cycle and apoptosis proteins [J].
Alisi, A ;
Demori, I ;
Spagnuolo, S ;
Pierantozzi, E ;
Fugassa, E ;
Leoni, S .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2005, 15 (1-4) :69-76
[2]   Survivin and IAP proteins in cell-death mechanisms [J].
Altieri, Dario C. .
BIOCHEMICAL JOURNAL, 2010, 430 :199-205
[3]  
Amiri Hamzeh, 2007, International Journal of Botany, V3, P321
[4]   New Guaiane Sesquiterpene Lactones from Ixeris dentata [J].
Cha, Mi-Ran ;
Choi, Yeon Hee ;
Choi, Chun Whan ;
Yoo, Dae Seok ;
Kim, Young Sup ;
Choi, Sang Un ;
Kim, Young Ho ;
Ryu, Shi Yong .
PLANTA MEDICA, 2011, 77 (04) :380-382
[5]   New chromosome counts in some species of Asteraceae from Iran [J].
Chehregani, Abdolkarim ;
Hajisadeghian, Somayeh .
NORDIC JOURNAL OF BOTANY, 2009, 27 (03) :247-250
[6]   Promoting apoptosis as a strategy for cancer drug discovery [J].
Fesik, SW .
NATURE REVIEWS CANCER, 2005, 5 (11) :876-885
[7]   What made sesquiterpene lactones reach cancer clinical trials? [J].
Ghantous, Akram ;
Gali-Muhtasib, Hala ;
Vuorela, Heikki ;
Saliba, Najat A. ;
Darwiche, Nadine .
DRUG DISCOVERY TODAY, 2010, 15 (15-16) :668-678
[8]   Age Sensitivity of NFκB Abundance and Programmed Cell Death in Erythrocytes Induced by NFKB Inhibitors [J].
Ghashghaeinia, Mehrdad ;
Cluitmans, Judith C. ;
Toulany, Mahmoud ;
Saki, Mohammad ;
Koeberle, Martin ;
Lang, Elisabeth ;
Dreischer, Peter ;
Biedermann, Tilo ;
Duszenko, Michael ;
Lang, Florian ;
Bosman, Giel J. ;
Wieder, Thomas .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2013, 32 (04) :801-813
[9]   The hallmarks of cancer A long non-coding RNA point of view [J].
Gutschner, Tony ;
Diederichs, Sven .
RNA BIOLOGY, 2012, 9 (06) :703-719
[10]   The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells [J].
Guzman, ML ;
Rossi, RM ;
Karnischky, L ;
Li, XJ ;
Peterson, DR ;
Howard, DS ;
Jordan, CT .
BLOOD, 2005, 105 (11) :4163-4169