A Phenylbutenoid Dimer, cis-3-(3′,4′-Dimethoxyphenyl)-4-[(E)-3′′′,4′′′-Dimethoxystyryl]Cyclohex-1-ene, Exhibits Apoptogenic Properties in T-Acute Lymphoblastic Leukemia Cells via Induction of p53-Independent Mitochondrial Signalling Pathway

被引:14
作者
Anasamy, Theebaa [1 ]
Abdul, Ahmad Bustamam [1 ]
Sukari, Mohd Aspollah [2 ]
Abdelwahab, Siddig Ibrahim [3 ,4 ]
Mohan, Syam [3 ]
Kamalidehghan, Behnam [3 ]
Azid, Mohd Zulkhairi [2 ]
Nadzri, Nabilah Muhammad [1 ]
Andas, A. Reenaa Joys [1 ]
Beng, Ng Kuan [1 ]
Hadi, A. Hamid A. [5 ]
Rahman, Heshu Sulaiman [1 ,6 ]
机构
[1] Univ Putra Malaysia, UPM MAKNA Canc Res Lab, Inst Biosci, Serdang 43400, Selangor, Malaysia
[2] Univ Putra Malaysia, Dept Chem, Fac Sci, Serdang 43400, Selangor, Malaysia
[3] Univ Malaya, Fac Med, Dept Pharm, Kuala Lumpur 50603, Malaysia
[4] Jazan Univ, Med Res Ctr, Fac Med, Jazan, Saudi Arabia
[5] Univ Malaya, Fac Sci, Kuala Lumpur 50603, Malaysia
[6] Univ Putra Malaysia, Dept Pathol & Microbiol, Fac Vet Med, Upm Serdang 43400, Selangor, Malaysia
关键词
HEAT-SHOCK-PROTEIN-70 INHIBITS APOPTOSIS; S-PHASE ARREST; DNA FRAGMENTATION; MEDICINAL-PLANTS; DRUG DISCOVERY; PROLIFERATION; CYTOTOXICITY; EXPRESSION; GROWTH; RHODAMINE-123;
D O I
10.1155/2013/939810
中图分类号
R [医药、卫生];
学科分类号
10 ;
摘要
The current study was designed to evaluate the in vitro cytotoxicity effect of a phenylbutenoid dimer, cis-3-(3',4'-dimethoxyphenyl)4-[(E)-3"',4"'-dimethoxystyryl]cyclohex-1-ene (ZC-B11) isolated from the rhizome of Zingiber cassumunar on various cancer cell line, and normal human blood mononuclear cells, and to further investigate the involvement of apoptosis-related proteins that leads, to the probable pathway in which apoptosis is triggered. Cytotoxicity test using MTT assay showed selective inhibition of ZC-B11 towards T-acute lymphoblastic leukemia cells, CEMss, with an IC50 value of 7.11 +/- 0.240 mu g/mL, which did not reveal cytotoxic effects towards normal human blood mononuclear cells (IC50 > 50 mu g/mL). Morphology assessments demonstrated distinctive morphological changes corresponding to a typical apoptosis. ZC-B11 also arrested cell cycle progression at S phase and causes DNA fragmentation in CEMss cells. Decline of mitochondrial membrane potential was also determined qualitatively. In the apoptosis-related protein determination, ZC-B11 was found to significantly upregulate Bax, caspase 3/7, caspase 9, cytochrome c, and SMAC and downregulate Bcl-2, HSP70, and XIAP, but did not affect caspase 8, p53, and BID. These results demonstrated for the first time the apoptogenic property of ZC-B11 on CEMss cell line, leading to the programmed cell death via intrinsic mitochondrial pathway of apoptosis induction.
引用
收藏
页数:14
相关论文
共 37 条
[1]   p53-independent apoptosis mediated by tachpyridine, an anti-cancer iron chelator [J].
Abeysinghe, RD ;
Greene, BT ;
Haynes, R ;
Willingham, MC ;
Turner, JL ;
Planalp, RP ;
Brechbiel, MW ;
Torti, FM ;
Torti, SV .
CARCINOGENESIS, 2001, 22 (10) :1607-1614
[2]   Evolution of anticancer drug discovery and the role of cell-based screening [J].
Balis, FM .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2002, 94 (02) :78-79
[3]   Drug discovery from medicinal plants [J].
Balunas, MJ ;
Kinghorn, AD .
LIFE SCIENCES, 2005, 78 (05) :431-441
[4]   Rhodamine 123 as a probe of mitochondrial membrane potential:: evaluation of proton flux through F0 during ATP synthesis [J].
Baracca, A ;
Sgarbi, G ;
Solaini, G ;
Lenaz, G .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2003, 1606 (1-3) :137-146
[5]   Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome [J].
Beere, HM ;
Wolf, BB ;
Cain, K ;
Mosser, DD ;
Mahboubi, A ;
Kuwana, T ;
Tailor, P ;
Morimoto, RI ;
Cohen, GM ;
Green, DR .
NATURE CELL BIOLOGY, 2000, 2 (08) :469-475
[6]   In vitro testing of the potential for orthopedic bone cements to cause apoptosis of osteoblast-like cells [J].
Ciapetti, G ;
Granchi, D ;
Savarino, L ;
Cenni, E ;
Magrini, E ;
Baldini, N ;
Giunti, A .
BIOMATERIALS, 2002, 23 (02) :617-627
[7]  
COLE SPC, 1986, CANCER CHEMOTH PHARM, V17, P259
[8]   Major DNA fragmentation is a late event in apoptosis [J].
Collins, JA ;
Schandl, CA ;
Young, KK ;
Vesely, J ;
Willingham, MC .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1997, 45 (07) :923-934
[9]   Apoptosome formation and caspase activation:: is it different in the heart? [J].
Czerski, L ;
Nuñez, G .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2004, 37 (03) :643-652
[10]  
DAVIS S, 1985, J BIOL CHEM, V260, P3844