Introduction: Gallic acid (GA) and curcumin (Cur) are natural phenolic compounds that their anti-tumor effects on many types of cancers have been proved. In the current study, the effect of the combination of these agents on MDA-MB-231 breast cancer cells was investigated. Methods: Inhibition of cell proliferation (MTT assay), light microscopy, fluorescence microscopy, cell cycle analysis, nitrite detection, ROS levels, measurement of the mitochondrial membrane potential, GSH level, Annexin V assay, RT-PCR and Western blotting methods were applied. Results: The results revealed the combination of GA and Cur strongly decreased MDA-MB-231 cell growth. Moreover, this combination increased ROS level and cytotoxic activity along with the glutathione depletion in MDA-MB-231 cells. Flow cytometry analysis showed the combination of GA and Cur increased sub-G1 cell population. Furthermore, fluorescent staining and Annexin V/PI assay showed that apoptotic cells were significantly increased in the presence of GA and Cur. At last, protein expression evaluation showed that the combination of GA and Cur significantly decreased Bcl-2 level while increased Bax, cleaved-caspase3 and PARP levels in MDA-MB-231 cells. Conclusion: These results suggest that GA in combination with Cur could be a possible candidate for chemoprevention agent of triple negative breast cancer.

No abstract

Breast cancer is a neoplastic disease with a high mortality rate among women. Recently, photodynamic therapy (PDT) and photothermal therapy (PTT) attracted considerable attention because of their minimal invasiveness. The PTT approach works based on hyperthermia generation, and PDT approach employs laser irradiation to activate a reagent named photosensitizer. Therefore, in the current paper, a dual-functioned nanocomposite (NC) was designed for the treatment of breast cancer model in Balb/c mice with the combination of photodynamic and photothermal approaches. Transmission electron microscopy, UV–visible spectroscopy, FTIR, and XRD were employed to validate the nanostructure and silica coating and curcumin (CUR) immobilization on the Fe3O4 nanoparticles. The effect of Fe3O4/SiO2-CUR combined with PDT and PTT was assessed in vivo on the breast tumor mice model, and immunohistochemistry (IHC) was employed to evaluate the expression of apoptotic Bax and Caspase3 proteins. The TEM images, UV–visible absorption, and FTIR spectra demonstrated the successful immobilization of curcumin molecules on the surface of Fe3O4/SiO2. Also, MTT assay confirmed the nontoxic nature of Fe3O4/SiO2 nanoparticles in vitro. In the breast tumor mice model, we have assessed six treatment groups, including control, CUR + PDT, Blue + NIR (near-infrared) lasers, NC, NC + PTT, and NC + PDT + PTT. The tumor volume in the NC + PDT + PTT group showed a significant reduction compared to other groups (p < 0.05). More interestingly, the tumor volume of NC + PDT + PTT group showed a 27% decrease compared to its initial amount. It should be noted that no detectable weight loss or adverse effects on the vital organs was observed due to the treatments. Additionally, the IHC data represented that the expression of proapoptotic Bax and Caspase3 proteins were significantly higher in the NC + PDT + PTT group compared to the control group, indicative of apoptosis. To conclude, our data supported the fact that the NC + PDT + PTT strategy might hold a promising substitute for chemotherapy for the treatment of triple-negative breast cancers.

Breast cancer is the leading cause of cancer death in women worldwide. Due to the side effects of current chemo‐reagents on healthy tissues, it is essential to search for alternative compounds with less toxicity and better efficacy. In the present study, we have investigated the anticancer effects of flavonoid xanthomicrol on the mice breast cancer model using MTT assay, cell cycle and Annexin/PI analysis, colony formation assay, H&E staining, immunohistochemistry, and miRNA analysis. Our results demonstrated that xanthomicrol decreased the cell viability and clonogenic capability, induced G1‐arrest and apoptosis in the breast cancer cells in vitro, and caused a significant reduction in the volume and weight of mice tumors in vivo. In addition, xanthomicrol reduced the expression of TNFα, VEGF, MMP9, and Ki67, while upregulating the expression of apoptotic markers such as Bax, caspase3, and caspase9. Finally, the expression of miR21, miR27, and miR125, known as oncomirs, decreased significantly after xanthomicrol administration, while the expression of miR29 and miR34, functioning as tumor suppressors, increased significantly (p < .001). Our data demonstrated that xanthomicrol can induce apoptosis and suppress angiogenesis in breast cancer cells due to its inhibitory effect on oncomirs and its stimulatory effect on tumor suppressor miRNAs.

MicroRNAs (miRNAs) with 20-30 nucleotides have recently emerged as the multidimensional regulators of cell fate decisions. Recent improvement in high-throughput sequencing has highlighted the potential role of LIN28/let-7 regulatory network in several developmental events. It was proposed that this pathway might represent a functional signature in cell proliferation, transition between commitment and pluripotency, and regulation of cancer and tumorigenicity. LIN28/let-7 regulatory pathway is one of the excellent examples of the relationship between an miRNA and mRNAs. This review article highlights the potentials of LIN28/let-7 signaling in gene regulatory pathways during pluripotency, reprogramming, and tumorigenicity.