國家衛生研究院 NHRI:Item 3990099045/14639

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/14639

Title:	BPR0C261, an analogous of microtubule disrupting agent D-24851 enhances the radiosensitivity of human non-small cell lung cancer cells via p53-dependent and p53-independent pathways
Authors:	Leu, JD;Lin, ST;Chen, CT;Chang, CA;Lee, YJ
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	(1) Destabilization of microtubule dynamics is a primary strategy to inhibit fast growing tumor cells. The low cytotoxic derivative of microtubule inhibitor D-24851, named BPR0C261 exhibits antitumor activity via oral administration. In this study, we investigated if BPR0C261 could modulate the radiation response of human non-small cell lung cancer (NSCLC) cells with or without p53 expression. (2) Different doses of BPR0C261 was used to treat human NSCLC A549 (p53+/+) cells and H1299 (p53-/-) cells. The cytotoxicity, radiosensitivity, cell cycle distribution, DNA damage, and protein expression were evaluated using an MTT assay, a colony formation assay, flow cytometry, a comet assay, and an immunoblotting analysis, respectively. (3) BPR0C261 showed a dose-dependent cytotoxicity on A549 cells and H1299 cells with IC(50) at 0.38 μM and 0.86 μM, respectively. BPR0C261 also induced maximum G(2)/M phase arrest and apoptosis in both cell lines after 24 h of treatment with a dose-dependent manner. The colony formation analysis demonstrated that a combination of low concentration of BPR0C261 and X-rays caused a synergistic radiosensitizing effect on NSCLC cells. Additionally, we found that a low concentration of BPR0C261 was sufficient to induce DNA damage in these cells, and it increased the level of DNA damage induced by a fractionation radiation dose (2 Gy) of conventional radiotherapy. Furthermore, the p53 protein level of A549 cell line was upregulated by BPR0C261. On the other hand, the expression of PTEN tumor suppressor was found to be upregulated in H1299 cells but not in A549 cells under the same treatment. Although radiation could not induce PTEN in H1299 cells, a combination of low concentration of BPR0C261 and radiation could reverse this situation. (4) BPR0C261 exhibits specific anticancer effects on NSCLC cells by the enhancement of DNA damage and radiosensitivity with p53-dependent and p53-independent/PTEN-dependent manners. The combination of radiation and BPR0C261 may provide an important strategy for the improvement of radiotherapeutic treatment.
Date:	2022-11-15
Relation:	International Journal of Molecular Sciences. 2022 Nov 15;23(22):Article number 14083.
Link to:	http://dx.doi.org/10.3390/ijms232214083
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000887425600001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85142855195
Appears in Collections:	[Chiung-Tong Chen] Periodical Articles

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