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

• Published in: Evidence-based complementary and alternative medicine 2013-01, Vol.2013 (2013), p.1-14
• Main Authors: Abdul, Ahmad Bustamam, Anasamy, Theebaa, Sukari, Mohd Aspollah, Abdel Wahab, Siddig Ibrahim, Mohan, Syam, Kamalidehghan, Behnam, Azid, Mohd Zulkhairi, Muhammad Nadzri, Nabilah, Andas, A. Reenaa Joys, Ng, Kuan Beng, Hadi, A. Hamid A., Sulaiman Rahman, Heshu
• Format: Article
• Language: English
• Subjects: Acute lymphoblastic leukemia; Apoptosis; BAX protein; Bcl-2 protein; Blood; Cancer; Caspase; Caspase-3; Caspase-8; Caspase-9; Cell cycle; Cell death; Chromatography; Cytochrome c; Cytotoxicity; DIABLO protein; DNA fragmentation; Hsp70 protein; Leukemia; Leukocytes (mononuclear); Lymphatic leukemia; Medical research; Membrane potential; Mitochondria; NMR; Nuclear magnetic resonance; p53 Protein; Penicillin; Proteins; S phase; Signal transduction; Toxicity testing; XIAP protein; Zingiber cassumunar
• ISSN: 1741-427X; 1741-4288
• DOI: 10.1155/2013/939810

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 μg/mL, which did not reveal cytotoxic effects towards normal human blood mononuclear cells (IC50 > 50 μg/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.