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