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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Dentatin induces apoptosis in prostate cancer cells via Bcl-2, Bcl-xL, Survivin downregulation, caspase-9, -3/7 activation, and NF-κB inhibition
Evidence-based Complementary and Alternative Medicine, Volume 2012, Article 856029, Year 2012
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Description
This study was set to investigate antiproliferative potential of dentatin (a natural coumarin isolated from Clausena excavata Burm. F) against prostate cancer and to delineate the underlying mechanism of action. Treatment with dentatin dose-dependently inhibited cell growth of PC-3 and LNCaP prostate cancer cell lines, whereas it showed less cytotoxic effects on normal prostate epithelial cell line (RWPE-1). The inhibitory effect of dentatin on prostate cancer cell growth was due to induction of apoptosis as evidenced by Annexin V staining and cell shrinkage. We found that dentatin-mediated accumulation of reactive oxygen species (ROS) and downregulated expression levels of antiapoptotic molecules (Bcl-2, Bcl-xL, and Survivin), leading to disruption of mitochondrial membrane potential (MMP), cell membrane permeability, and release of cytochrome c from the mitochondria into the cytosol. These effects were associated with induction of caspase-9, -3/7 activities, and subsequent DNA fragmentation. In addition, we found that dentatin inhibited TNF-α-induced nuclear translocation of p65, suggesting dentatin as a potential NF-κB inhibitor. Thus, we suggest that dentatin may have therapeutic value in prostate cancer treatment worthy of further development. © 2012 Ismail Adam Arbab et al.
Authors & Co-Authors
Arbab, Ismail Adam
Malaysia, Serdang
Universiti Putra Malaysia
Looi, Chung Yeng
Malaysia, Kuala Lumpur
Universiti Malaya
Abdul, Ahmad Bustamam Hj
Malaysia, Serdang
Universiti Putra Malaysia
Cheah, Foo Kit
Malaysia, Kuala Lumpur
Universiti Malaya
Wong, Won Fen
Japan, Sendai
Tohoku University
Sukari, Mohd Aspollah Hj Md
Malaysia, Serdang
Universiti Putra Malaysia
Rasedee, Abdullah Bin
Malaysia, Serdang
Universiti Putra Malaysia
Mohan, Syam Morali
Malaysia, Kuala Lumpur
Universiti Malaya
Syam, Suvitha
Malaysia, Kuala Lumpur
Universiti Malaya
Arya, Aditya
Malaysia, Kuala Lumpur
Universiti Malaya
Mohamed Elhassan Taha, Manal Mohamed Elhassan
Malaysia, Serdang
Universiti Putra Malaysia
Moharram, Bushra Abdulkarim
Malaysia, Kuala Lumpur
Universiti Malaya
Mustafa, Mohd Rais
Malaysia, Kuala Lumpur
Universiti Malaya
Abdelwahab, Siddig Ibarhim
Saudi Arabia, Jazan
Jazan University
Statistics
Citations: 60
Authors: 14
Affiliations: 4
Identifiers
Doi:
10.1155/2012/856029
ISSN:
1741427X
e-ISSN:
17414288
Research Areas
Cancer
Genetics And Genomics