title: 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.
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 IC50 value of 7.11 ± 0.240  μ g/mL, which did not reveal cytotoxic effects towards normal human blood mononuclear cells (IC50 > 50  μ 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.
authors.affiliation: UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Theebaa
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authors.lastname: Anasamy
authors.forename: Ahmad Bustamam
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authors.lastname: Abdul
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authors.forename: Siddig Ibrahim
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authors.lastname: Abdelwahab
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authors.lastname: Mohan
authors.forename: Behnam
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authors.lastname: Kamalidehghan
authors.forename: Mohd Zulkhairi
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authors.forename: Nabilah
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authors.lastname: Muhammad Nadzri
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authors.lastname: Hadi
authors.forename: Heshu
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authors.lastname: Sulaiman Rahman