mir-451a-5p Modulates Breast Cancer Cell Apoptosis, Migration, and Chemosensitivity to Carboplatin through the PTEN Pathway

Background: MicroRNAs (miRNAs) can play essential roles in the modulation of cancer cell growth, survival, and resistance to chemotherapy. Thus, we hypothesized that restoration of miR-451a-5p (a tumor suppressor) might affect sensitivity to chemotherapeutics in breast cancer cells. Methods: For this purpose, malignant breast cancer cells (MDA-MB-231) were transfected with miR-451a-5p mimic and exposed with carboplatin. Then, the apoptotic rate was evaluated by flow cytometry and DAPI staining (apoptosis), q-RT-PCR (expression levels of caspase-3, caspase-8, MMP9, ROCK, vimentin, c-Myc genes). Moreover, the proliferation and migration of cancer cells were assessed by MTT (cell viability) and wound healing assay. The western blot assay was used for protein expression of PTEN, AKT, and P-AKT. Results: Our findings demonstrated that a combination of miR-451a-5p restoration with carboplatin administration could additionally induce apoptosis, repress the proliferation and migration, and also increase PTEN protein expression with no significant alteration on the AKT/P-AKT protein expressions in the breast cancer cells. The present data was analyzed using GraphPad Prism 6 software by non-parametric one-way ANOVA and t-test. Conclusion: In conclusion, it seems that overexpression of miR-451a can enhance the chemosensitivity of breast cancer cells to carboplatin therapy. Thus, it may shed new light on miR-451a management of breast cancer chemoresistance and may be a beneficial strategy for future cancer therapy. However, further studies, particularly in other signaling pathways, should be required

A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid on 5637 (bladder cancer) and 4T1 (Breast cancer) cell lines

Context: Anticancer properties of artemisinin and its derivatives have been shown in many experiments. Aims: Addition of butyric acid, miconazole, and iron to this traditional drug has been done in order to enhance its anticancer potency. Materials and Methods: Cell lines 5637 and 4T1, were cultivated and classified into 13 groups of three each. Different doses of artemisinin with constant doses of iron, miconazole and butyric acid, were added to the cultures. At the end of exposure pathological and enzymatic studies were performed. Results: In four groups treated with different doses of artemisinin and iron, dose-dependent changes were observed. These changes included apoptosis and necrosis with dominance of apoptosis. The supernatant lactate dehydrogenase (LDH) level was increased in a dose-dependent manner, but there was no significant increase in the cell fraction of malonyldialdehyde (MDA) or LDH. In four other groups, which received miconazole, butyric acid and iron in addition to different doses of artemisinin, necrosis was more prominent than apoptosis, and the MDA level did not show any significant change, but LDH was increased. The groups treated with miconazole showed identical changes, with less severity compared to combination therapy groups. In butyric acid-treated groups, the only detectable changes were, mild cell swelling, few apoptosis, and rare necrosis. Conclusions: A combination therapy with artemisinin can be more effective against cancer cells than monotherapy with that. Butyric acid was not effective on cancer cells. Miconazole deviated the nature of cell death from apoptosis to necrosis and it must be used under caution