Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent Apoptosis
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 xeno...
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Series: | Evidence-Based Complementary and Alternative Medicine |
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doaj-7c224357889e454893716ae7961212462020-11-24T23:42:19ZengHindawi LimitedEvidence-Based Complementary and Alternative Medicine1741-427X1741-42882013-01-01201310.1155/2013/468537468537Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent ApoptosisHongbo Wang0Pengfei Yu1Jing Bai2Jianqiao Zhang3Liang Kong4Fangxi Zhang5Guangying Du6Shiqian Pei7Lixia Zhang8Yongtao Jiang9Jingwei Tian10Fenghua Fu11Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, ChinaCenter of Basic Medicine, Binzhou Medical College, Yantai 264005, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, ChinaThe 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.http://dx.doi.org/10.1155/2013/468537 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hongbo Wang Pengfei Yu Jing Bai Jianqiao Zhang Liang Kong Fangxi Zhang Guangying Du Shiqian Pei Lixia Zhang Yongtao Jiang Jingwei Tian Fenghua Fu |
spellingShingle |
Hongbo Wang Pengfei Yu Jing Bai Jianqiao Zhang Liang Kong Fangxi Zhang Guangying Du Shiqian Pei Lixia Zhang Yongtao Jiang Jingwei Tian Fenghua Fu Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent Apoptosis Evidence-Based Complementary and Alternative Medicine |
author_facet |
Hongbo Wang Pengfei Yu Jing Bai Jianqiao Zhang Liang Kong Fangxi Zhang Guangying Du Shiqian Pei Lixia Zhang Yongtao Jiang Jingwei Tian Fenghua Fu |
author_sort |
Hongbo Wang |
title |
Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent Apoptosis |
title_short |
Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent Apoptosis |
title_full |
Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent Apoptosis |
title_fullStr |
Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent Apoptosis |
title_full_unstemmed |
Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent Apoptosis |
title_sort |
ocotillol enhanced the antitumor activity of doxorubicin via p53-dependent apoptosis |
publisher |
Hindawi Limited |
series |
Evidence-Based Complementary and Alternative Medicine |
issn |
1741-427X 1741-4288 |
publishDate |
2013-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2013/468537 |
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