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Silibinin sensitizes chemo-resistant breast cancer cells to chemotherapy.


ABSTRACT: 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.To evaluate the effects of silibinin on enhancing the sensitivity of chemo-resistant human breast cell lines to doxorubicin (DOX) and paclitaxel (PAC).The cells were treated with silibinin (at 50 to 600??M 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??M concentration) were evaluated by mammosphere assay.Silibinin exerted significant growth inhibitory effects with IC50 ranging from 200 to 570??M in different cell lines. Treatment of DOX-resistant MDA-MB-435 cells with silibinin at 200??M reduced DOX IC50 from 71 to 10??g/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??M 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??M concentration generated synergistic effects when it was used in combination with PAC at 250?nM concentration (CI?=?0.81).Silibinin sensitizes chemo-resistant cells to chemotherapeutic agents and can be useful in treating breast cancers.

SUBMITTER: Molavi O 

PROVIDER: S-EPMC6130726 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Silibinin sensitizes chemo-resistant breast cancer cells to chemotherapy.

Molavi Ommoleila O   Narimani Farzaneh F   Asiaee Farshid F   Sharifi Simin S   Tarhriz Vahideh V   Shayanfar Ali A   Hejazi Mohammadsaied M   Lai Raymond R  

Pharmaceutical biology 20171201 1


<h4>Context</h4>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.<h4>Objective</h4>To evaluate the effects of silibinin on enhancing the sensitivity of chemo-resistant human breast cell lines to doxorubicin (DOX) and paclitaxel (PAC).<h4>Materials and methods</h4>The cells were treated with silibinin (at 50 to 600   ...[more]

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