Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells (original) (raw)
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Iranian Journal of Basic Medical Sciences, 2021
Objective(s): Recently, there is a significant focus on combination chemotherapy for cancer using a cytotoxic drug and a phytochemical compound. We investigated the effect of silibinin on etoposide-induced apoptosis in MCF-7 and MDA-MB-231 breast carcinoma cell lines.Materials and Methods: The cytotoxic effects of silibinin and etoposide were determined using MTT assay after 24 and 48 hr incubation with these drugs individually and combined. The mRNA expression of Bax and Bcl2, and protein levels of P53, phosphorylated p53 (P-P53), and P21 were determined using real-time PCR and western blot analysis, respectively. The caspase 9 activity was measured using an ELISA kit. Results: Silibinin and etoposide alone and combined significantly inhibit cell growth in a dose and time-dependent manner in both cell lines. The strongest synergistic effects in terms of MCF-7 cell growth inhibition [combination index (CI) = 0.066] were evident. The silibinin-etoposide combinations cause a much powe...
European Online Journal of Natural and Social Sciences, 2014
Given the prevalence of breast cancer, the mortality of patients and the public's convenient access to the herbal extract of milk thistle, we decided to examine the effectiveness of this plant's components on the breast cancer cell line MCF-7. Silibinin is a naturally occurring flavonoid antioxidant found in the milk thistle. Recently, it has demonstrated potent, anti-proliferative effects against various malignant cell lines. In the present study, MCF-7 cells were incubated and treated with various concentrations of silibinin repeatedly. The degree of cell cytotoxicity depended on the dose of the milk thistle's extract and also on the duration of its exposure, imparting an inhibitory effect on the viability of metastatic MCF-7 cells. Finally, the expression of apoptotic genes (BCL-2 and BAX) was assessed by Real time PCR. Cell viability and growth of MCF-7 cell lines were inhibited by silibinin. The results of the present study confirm the efficacy of the herbal supplement against breast cancer. Due to the nature of the product, its low cost and potential accessibility to the public, adding this herbal supplement to the human food diet may be effective in preventing and treating breast cancer.
Asian Pacific journal of cancer prevention : APJCP, 2016
Silibinin is a natural polyphenol with high antioxidant and anticancer properties. In this study, its influence on two of the most commonly employed human breast cancer cell lines, MCF-7 and T47D, and one non-malignant MCF-10A cell line, were investigated and compared. Cell viability, the cell cycle distribution and apoptosis induction were analyzed by MTT and flow cytometry, respectively. The effect of silibinin on PTEN, Bcl-2, P21, and P27 mRNAs expression was also investigated by real-time RT-PCR. It was found that silibinin caused G1 cell cycle arrest in MCF-7 and MCF-10A cells but had no effect on the T47D cell cycle. Silibinin induced cytotoxic and apoptotic effects in T47D cells more than the MCF-7 cells and had no cytotoxic effect in MCF-10A cells under the same conditions. Silibinin upregulated PTEN in MCF-7 and caused slightly increased P21 mRNA expression in T47D cells and slightly increased PTEN and P21 expression in MCF-10A cells. Bcl-2 expression decreased in all of th...
Acta Pharmacologica Sinica, 2007
The chemotherapeutic and cytotoxic effects of alkylating agents are directly related to the formation of carbonium ion intermediates or related transition complexes that alkylate DNA [3,4]. The potential of these drugs to induce cell death via interference with DNA integrity in fast proliferating tissues forms the basis for their therapeutic and toxic properties [3,4]. Platinum complexes do not alkylate DNA;
Silibilin-Induces Apoptosis in Breast Cancer Cells by Modulating p53, p21, Bak and Bcl-xl Pathways
Asian Pacific journal of cancer prevention : APJCP, 2015
Nowadays herbal-derived medicines are attracting attention as new sources of drugs with few side effects. Silibinin is a flavonoid compound with chemotheraputic effects on different cancers such as examples in the prostate, lung, colon and breast. In the present study, the cytotoxic effects of silibinin on MCF7 breast cancer cells were investigated. Apoptosis was determined by flow cytometry and the impact of silibinin on the expression of pivotal genes including Bak, P53, P21, BRCA1, BCL-X1 and ATM was analyzed. Treatment for 24h had a significant dose-dependent inhibitory effect on cell growth (p<0.05) with dose- and time- dependent induction of apoptosis (p<0.05). In addition, there were significant increases in BRCA1, ATM, Bak and Bcl-XL gene expression at the mRNA level with different concentrations of silibinin for 24 or 48 h (p<0.05). Taken together, the results suggest that silibinin inhibits the proliferation and induces apoptosis of MCF-7 cells by down-regulating ...
Clinical cancer research : an official journal of the American Association for Cancer Research, 2002
We recently demonstrated the strong anticancer efficacy of silibinin,an active constituent of a widely consumed dietary supplement milk thistle extract, against human prostate cancer cells in culture and nude mice xenografts. We also observed that pharmacologically achievable concentrations of silibinin in animal studies were in the range of 25-100 microM, depending on the dose regimen, which did not show any apparent toxicity to the animals. In this study, we assessed whether silibinin synergizes the therapeutic potential of the chemotherapeutic drug doxorubicin against prostate cancer, the effectiveness of which is limited because of high systemic toxicity. Prostate cancer cells were treated with silibinin and doxorubicin, either alone or in combination, and cell growth was determined by manual cell counting. Cell cycle progression was assessed by saponin/propidium iodide staining and fluorescence-activated cell sorter analysis. Protein levels of cell cycle regulators were determi...
Anti-cancer Effects of Silibinin: The Current Status in Cancer Chemoprevention
Natural Products for Cancer Chemoprevention
The naturally occurring flavonolignan Silibinin (also known as Silybin) is a bioactive constituent of silymarin isolated from the seeds of the milk thistle plant (Silybum marianum L. Gaernt.), a member of the Asteraceae family. The milk thistle plant is a part of the native vegetation in Southern Europe, Southern Russia, Asia Minor and Northern Africa. This multi-functional flavonolignan possesses strong hepatoprotective, cardioprotective, neuroprotective, immune-modulatory, antidotal and anti-neoplastic properties. To date, over 600 peer-reviewed research reports and limited clinical trials have evaluated the anti-oncogenic efficacy of silibinin to combat tumor growth, angiogenesis, and metastasis. As a promising agent, silibinin mediates a wide-range of potent chemopreventive and anti-cancer activities in several frequently diagnosed epithelial malignancies, including skin, colon, prostate and lung. In addition, several combinatorial anti-cancer strategies of silibinin with other therapeutics exhibit synergistic interactions to suppress drug-induced toxic effects and chemoresistance. In this chapter, the pre-clinical and clinical efficacy of silibinin and/or silymarin derivatives against several cancers will be reviewed. Moreover, the chapter will summarize silibinin effects on key signaling pathways, such as: transforming Growth Factor beta (TGFβ), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), and NF-κB (nuclear factor-kappa B), which are crucial to the anti-cancer activity of silibinin in cancer prevention, disease progression/recurrence and reversal of drug resistance.
Molecular Cancer Therapeutics, 2009
Colorectal cancer is one of the leading causes of cancerrelated morbidity and mortality. The use of nontoxic phytochemicals in the prevention and intervention of colorectal cancer has been suggested as an alternative to chemotherapy. Here we assessed the anticancer efficacy of silibinin against advanced colorectal cancer LoVo cells both in vitro and in vivo. Our results showed that silibinin treatment strongly inhibits the growth of LoVo cells (P < 0.05-0.001) and induces apoptotic death (P < 0.01-0.001), which was associated with increased levels of cleaved caspases (3 and 9) and cleaved poly (ADP-ribose) polymerase. Additionally, silibinin caused a strong cell cycle arrest at G 1 phase and a slight but significant G 2 -M-phase arrest at highest concentration (P < 0.01-0.001). Molecular analyses for cell cycle regulators showed that silibinin decreases the level of cyclins (D1, D3, A and B1) and cyclin-dependent kinases (1, 2, 4, and 6) and increases the level of cyclin-dependent kinase inhibitors (p21 and p27). Consistent with these results, silibinin treatment also decreased the phosphorylation of retinoblastoma protein at Ser 780 , Ser 795 , and Ser 807 /Ser 811 sites without significantly affecting its total level. In animal studies, oral administration of silibinin for 6 weeks (at 100 and 200 mg/kg/d for 5 days/wk) significantly inhibited the growth of LoVo xenograft (P < 0.001) in athymic nude mice without any apparent toxicity. Analyses of xenograft tissue showed that silibinin treatment inhibits proliferation and increases apoptosis along with a strong increase in p27 levels but a decrease in retinoblastoma phosphorylation. Together, these results suggest the potential use of silibinin against advanced human colorectal cancer.
Synergistic Anticancer Effects of Silibinin and Chrysin in T47D Breast Cancer Cells
Asian Pacific journal of cancer prevention : APJCP, 2017
Objective: Breast cancer is one of the most significant causes of female cancer death worldwide. Although several chemotherapeutics have been developed to treat this type of cancer, issues remain such as low survival rates and high reoccurrence after chemotherapy and radiotherapy. To explore a chemopreventive approach to enhancing breast cancer treatment efficacy, the antiproliferative effects of a combination of chrysin and silibinin, two herbal substances, in T47D breast cancer cells were assessed. Materials and Methods: Cytotoxicity of the agents singly and in combination was evaluated by MTT assay. Also, qRT-PCR was used to measure the expression levels of hTERT and cyclin D1 genes after 48 h treatment. Results: Cell viability assays revealed that chrysin or silibinin alone inhibited proliferation in a dose and time-dependent manner, and combining the drugs synergistically induced growth inhibition in the breast cancer cell line. The precise nature of this interaction was furthe...
Leukemia Research, 2014
Silibinin have been introduced for several years as a potent antioxidant in the field of nutraceuticals. Based on wide persuasive effects of this drug, we have decided to investigate the effects of silibinin on chronic myelogenous leukemia (CML) in vitro models, K562 and KCL22 cell lines. Lactate dehydrogenase (LDH) release, microculture tetrazolium test (MTT assay) and real-time PCR were employed to evaluate the effects of silibinin on cell cytotoxicity, cell proliferation and expression of various multidrug resistance genes in these cell lines, respectively. Our results have shown that presence of silibinin has inhibitory effects on cell proliferation of K562 and KCL22 cell lines. Also, our data indicated that silibinin, in a dosedependent manner with applying no cytotoxic effects, inhibited cell proliferation and reduced mRNA expression levels of some transporter genes e.g. MDR1, MRP3, MRP2, MRP1, MRP5, MRP4, ABCG2, ABCB11, MRP6 and MRP7. The multifarious in vitro inhibitory effects of silibinin are in agreement with growing body of evidence that silibinin would be an efficient anticancer agent in order to be used in multi-target therapy to prevail the therapeutic hold backs against CML.