Back to Browse Journals » OncoTargets and Therapy » Volume 10

Apoptotic induction and inhibition of NF-κB signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from Litsea costalis: an in vitro study

Authors Abbaspour Babaei M, Zaman Huri H, Kamalidehghan B, Yeap SK, Ahmadipour F

Received 21 December 2015

Accepted for publication 9 August 2016

Published 10 January 2017 Volume 2017:10 Pages 277—294

DOI https://doi.org/10.2147/OTT.S102894

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ashok Kumar Pandurangan

Peer reviewer comments 2

Editor who approved publication: Dr Faris Farassati

Maryam Abbaspour Babaei,1 Hasniza Zaman Huri,1,2 Behnam Kamalidehghan,3,4 Swee Keong Yeap,5,6 Fatemeh Ahmadipour1

1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Clinical Investigation Centre (CIC), University of Malaya Medical Centre, Kuala Lumpur, Malaysia; 3Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Medical Genetics Department, National Institute for Genetics Engineering and Biotechnology (NIGEB), Tehran, Iran; 5Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia; 6Xiamen University Malaysia, Sepang, Malaysia

Abstract: Litsea is considered as an evergreen genus distributed in tropical and subtropical Asia; this genus belongs to the large family of Lauraceae. In this study, the cell-death metabolism of biseugenol B was investigated. Nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and release of cytochrome c have been detected in human prostate cancer cell line (PC3) treated with biseugenol B by high content screening (HCS). Fluorescent analysis was conducted to examine the reactive oxygen species formation. To determine the mechanism of cell death, the levels of Bcl-cell lymphoma (Bcl)-2 proteins, Bcl-2-associated X (Bax) protein and anti-apoptosis heat-shock protein 70 were tested by applying reverse transcription polymerase chain reaction and Western blot. Bioluminescent assays were also performed to assess the level of caspases such as 3/7, 8 and 9 during treatment. Furthermore, the involvement of nuclear factor kappa-B (NF-κB) was examined by Western blot and HCS. Biseugenol B showed significant cytotoxicity toward PC3 with no toxicity toward normal prostate cells (RWPE-1), which indicates that biseugenol B has qualities that induce apoptosis in tumor cells. The treatment of PC3 cells with biseugenol B provoked apoptosis with cell-death-transducing signals. Downregulation of Bcl-2 and upregulation of Bax regulated the MMP, which in turn caused the release of cytochrome c from mitochondria into cytosol. The release of cytochrome c activated caspase-9, which consequently activated caspase-3/7 with the cleaved poly(ADP-ribose) polymerase protein, thereby resulting in apoptosis alteration. Involvement of an extrinsic apoptosis pathway was exhibited by the increase in caspase-8, while the increase in caspase-3/7 and caspase-9 demonstrated involvement of an intrinsic apoptosis pathway. Meanwhile, no significant increase was observed in caspases 3/7, 8 or 9 in normal prostate cells (RWPE-1) after treatment with biseugenol B. Prevention of NF-κB translocation from the cytosol to the nucleus occurred in PC3 after treatment with biseugenol B. The results of our study reveal that biseugenol B triggers the apoptosis of PC3 cells via intrinsic and extrinsic apoptosis pathways and inhibition of NF-κB signaling pathway. Our findings suggest that biseugenol B is a potentially useful agent for prostate cancer treatment.

Keywords: biseugenol B, apoptosis, mitochondria, caspase, intrinsic, extrinsic, NF-κB

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other article by this author:

Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells

Abbaspour Babaei M, Kamalidehghan B, Saleem M, Huri HZ, Ahmadipour F

Drug Design, Development and Therapy 2016, 10:2443-2459

Published Date: 1 August 2016