Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.canlet.2016.07.023
Title: A novel combinatorial strategy using Seliciclib (R) and Belinostat (R) for eradication of non-small cell lung cancer via apoptosis induction and BID activation
Authors: Ong, Pei-Shi 
Wang, Lingzhi 
Chia, Deborah Miao-Hui
Seah, Jolyn Yu-Xin
Kong, Li-Ren 
Thuya, Win-Lwin 
Chinnathambi, Arunachalam
Lau, Jie-Ying Amelia 
Wong, Andrea Li-Ann 
Yong, Wei-Peng 
Yang, Daiwen 
Ho, Paul Chi-Lui 
Sethi, Gautam 
Goh, Boon-Cher 
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Belinostat (R)
Seliciclib (R)
Non-small cell lung cancer
Caspase-8 activation
Truncated BID
HISTONE DEACETYLASE INHIBITORS
DEPENDENT KINASE INHIBITOR
DEATH
P53
FLAVOPIRIDOL
ENHANCEMENT
CARBOPLATIN
ROSCOVITINE
EXPRESSION
PACLITAXEL
Issue Date: 10-Oct-2016
Publisher: ELSEVIER IRELAND LTD
Citation: Ong, Pei-Shi, Wang, Lingzhi, Chia, Deborah Miao-Hui, Seah, Jolyn Yu-Xin, Kong, Li-Ren, Thuya, Win-Lwin, Chinnathambi, Arunachalam, Lau, Jie-Ying Amelia, Wong, Andrea Li-Ann, Yong, Wei-Peng, Yang, Daiwen, Ho, Paul Chi-Lui, Sethi, Gautam, Goh, Boon-Cher (2016-10-10). A novel combinatorial strategy using Seliciclib (R) and Belinostat (R) for eradication of non-small cell lung cancer via apoptosis induction and BID activation. CANCER LETTERS 381 (1) : 49-57. ScholarBank@NUS Repository. https://doi.org/10.1016/j.canlet.2016.07.023
Abstract: © 2016 Elsevier Ireland Ltd With conventional anticancer agents for non-small cell lung cancer (NSCLC) reaching therapeutic ceiling, the novel combination using histone deacetylase inhibitor, PXD101 (Belinostat®), and CDK inhibitor, CYC202 (Seliciclib®), was investigated as an alternative anticancer strategy. At clinically achievable concentration of CYC202 (15 µM), combination therapy resulted in significant reduction in cell proliferation (IC50 = 3.67 ± 0.80 µM, p < 0.05) compared with PXD101 alone (IC50 = 6.56 ± 0.42 µM) in p53 wild-type A549 cells. Significant increase in apoptosis that occurred independently of cell cycle arrest was observed after concurrent treatment. This result was corroborated by greater formation of cleaved caspase-8, caspase-3 and PARP. Up-regulation of p53 and truncated BID protein levels was seen while Mcl-1 and XIAP protein levels were down-regulated upon combined treatment. Further analysis of apoptotic pathways revealed that caspase inhibitors, but not p53 silencing, significantly abrogated the cytotoxic enhancement. Moreover, the enhanced efficacy of this combination was additionally confirmed in p53 null H2444 cells, suggesting the potential of this combination for treatment of NSCLC that are not amenable to effects of conventional p53-inducing agents.
Source Title: CANCER LETTERS
URI: https://scholarbank.nus.edu.sg/handle/10635/175510
ISSN: 03043835
18727980
DOI: 10.1016/j.canlet.2016.07.023
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