title: Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent Apoptosis.
abstract: The use of doxorubicin (Dox) was severely constrained by dose-dependent side effects, which might be attenuated by combining a "sensitizer" to decrease its cumulative dosage. In this study, it was investigated whether ocotillol could enhance the antiproliferation activity of Dox. MTT assays and xenograft tumor model were firstly conducted to evaluate the effect of ocotillol on the antitumor activity of Dox. Flow cytometry and Hoechst staining assays were then performed to assess cell apoptosis. Western blot and real-time PCR were finally used to detect the expression of p53 and its target genes. Our results showed ocotillol to enhance Dox-induced cell death in p53 wild-type cancer cells. Compared with Dox alone, Dox with ocotillol (Dox-O) could induce much more cell apoptosis and activate p53 to a much greater degree, which in turn markedly increased expression of proapoptosis genes. The enhanced cytotoxic activity was partially blocked by pifithrin- α , which might be through attenuating the increased apoptosis. Furthermore, ocotillol significantly increased the antitumor activity of Dox in A549 xenograft tumor in nude mice. These findings indicated that ocotillol could potentiate the cytotoxic effect of Dox through p53-dependent apoptosis and suggested that coadministration of ocotillol with Dox might be a potential therapeutic strategy.
authors: Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, China.
authors: Hongbo
authors: H
authors: Wang
authors: Pengfei
authors: P
authors: Yu
authors: Jing
authors: J
authors: Bai
authors: Jianqiao
authors: J
authors: Zhang
authors: Liang
authors: L
authors: Kong
authors: Fangxi
authors: F
authors: Zhang
authors: Guangying
authors: G
authors: Du
authors: Shiqian
authors: S
authors: Pei
authors: Lixia
authors: L
authors: Zhang
authors: Yongtao
authors: Y
authors: Jiang
authors: Jingwei
authors: J
authors: Tian
authors: Fenghua
authors: F
authors: Fu
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