A Phenylbutenoid Dimer, cis-3-(3 %26apos;,4 %26apos;-Dimethoxyphenyl)-4-[(E)-3 %26apos;%26apos;%26apos;,4 %26apos;%26apos;%26apos;-Dimethoxystyryl]Cyclohex-1-ene, Exhibits Apoptogenic Properties in T-Acute Lymphoblastic Leukemia Cells via Induction of p53-Independent Mitochondrial Signalling Pathway

作者：Anasamy Theebaa; Abdul Ahmad Bustamam^*; Sukari Mohd Aspollah; Abdelwahab Siddig Ibrahim; Mohan Syam; Kamalidehghan Behnam; Azid Mohd Zulkhairi; Nadzri Nabilah Muhammad; Andas A Reenaa Joys; Beng Ng Kuan; Hadi A Hamid A; Rahman Heshu Sulaiman

来源：Evidence-Based Complementary and Alternative Medicine, 2013, 2013: 939810.

DOI：10.1155/2013/939810

The current study was designed to evaluate the in vitro cytotoxicity effect of a phenylbutenoid dimer, cis-3-(3%26apos;,4%26apos;-dimethoxyphenyl)4-[(E)-3%26quot;%26apos;,4%26quot;%26apos;-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 %26gt; 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.

• 出版日期2013