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

Author:

Anasamy Theebaa1,Abdul Ahmad Bustamam1,Sukari Mohd Aspollah2,Abdelwahab Siddig Ibrahim34,Mohan Syam3ORCID,Kamalidehghan Behnam3,Azid Mohd Zulkhairi2,Muhammad Nadzri Nabilah1,Andas A. Reenaa Joys1,Kuan Beng Ng1,Hadi A. Hamid A.5,Sulaiman Rahman Heshu16

Affiliation:

1. UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia

2. Department of Chemistry, Faculty of Science, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia

3. Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia

4. Medical Research Center, Faculty of Medicine, Jazan University, Jazan, P.O. Box 114, Saudi Arabia

5. Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

6. Department of Microbiology and Pathology, Faculty of Veterinary Medicine, University Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

Abstract

The current study was designed to evaluate thein vitrocytotoxicity effect of a phenylbutenoid dimer,cis-3-(3′,4′-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene (ZC-B11) isolated from the rhizome ofZingiber cassumunaron 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 IC50value of7.11±0.240μg/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.

Funder

Ministry of Higher Education, Malaysia

Publisher

Hindawi Limited

Subject

Complementary and alternative medicine

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