Abstract

Context: Multiple drug resistance is the major obstacle to conventional chemotherapy. Silibinin, a nontoxic naturally occurring compound, has anticancer activity and can increase the cytotoxic effects of chemotherapy in various cancer models.

Objective: To evaluate the effects of silibinin on enhancing the sensitivity of chemo-resistant human breast cell lines to doxorubicin (DOX) and paclitaxel (PAC).

Materials and methods: The cells were treated with silibinin (at 50 to 600 μM concentrations) and/or chemo drugs for 24 and 48 h, then cell viability and changes in oncogenic proteins were determined by MTT assay and Western blotting/RT-PCR, respectively. Flow cytometry was used to study apoptosis in the cells receiving different treatments. The antitumorigenic effects of silibinin (at 200 to 400 μM concentration) were evaluated by mammosphere assay.

Results: Silibinin exerted significant growth inhibitory effects with IC50 ranging from 200 to 570 μM in different cell lines. Treatment of DOX-resistant MDA-MB-435 cells with silibinin at 200 μM reduced DOX IC50 from 71 to 10 μg/mL and significantly suppressed the key oncogenic pathways including STAT3, AKT, and ERK in these cells. Interestingly treatment of DOX-resistant MDA-MB-435 cells with silibinin at 400 μM concentration for 48 h induced a 50% decrease in the numbers of colonies as compared with DMSO-treated cells. Treatment of PAC-resistant MCF-7 cells with silibinin at 400 μM concentration generated synergistic effects when it was used in combination with PAC at 250 nM concentration (CI = 0.81).

Conclusion: Silibinin sensitizes chemo-resistant cells to chemotherapeutic agents and can be useful in treating breast cancers.

Details

Title
Silibinin sensitizes chemo-resistant breast cancer cells to chemotherapy
Author
Molavi, Ommoleila 1 ; Narimani, Farzaneh 2 ; Asiaee, Farshid 2 ; Sharifi, Simin 2 ; Tarhriz, Vahideh 2 ; Shayanfar, Ali 2 ; Hejazi, Mohammadsaied 2 ; Lai, Raymond 3 

 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;; Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran;; Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada 
 Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; 
 Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada 
Pages
729-739
Publication year
2017
Publication date
Dec 2017
Publisher
Taylor & Francis Ltd.
ISSN
13880209
e-ISSN
17445116
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2195293436
Copyright
© 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.