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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

Anasamy, Theebaa and Abdul, Ahmad Bustamam and Sukari, Mohd Aspollah and Abdelwahab, Siddig Ibrahim and Mohan, Syam and Kamalidehghan, Behnam and Azid, Mohd Zulkhairi and Muhammad Nadzri, Nabilah and Andas, A. Reenaa Joys and Beng, Ng Kuan and A. Hadi, A. Hamid and Rahman, Heshu Sulaiman (2013) 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. Evidence-Based Complementary and Alternative Medicine, 2013 (939810). pp. 1-14. ISSN 1741-427X; ESSN: 1741-4288

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Official URL: http://dx.doi.org/10.1155/2013/939810

Abstract

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 ICvalue of 7.11 ± 0.240 g/mL, which did not reveal cytotoxic effects towards normal human blood mononuclear cells (IC> 50 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.

Item Type:Article
Keyword:Phenylbutenoid dimer; Acute lymphoblastic leukemia; Antileukemic agent
Faculty or Institute:Faculty of Science
Faculty of Veterinary Medicine
Institute of Bioscience
Publisher:Hindawi Publishing Corporation
DOI Number:10.1155/2013/939810
ID Code:30040
Deposited By: Umikalthom Abdullah
Deposited On:19 Jun 2014 08:53
Last Modified:12 Feb 2016 16:13

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