cyclin-d1 and chrysin

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer, accounting for 20% of cases. Due to the lack of a molecular target, limited options are available for TNBC treatment. Radiation therapy (RT) is a treatment modality for the management of TNBC following surgery; however, it has a detrimental effect on surrounding healthy tissues/cells at a higher rate.. We examined the effect of RT in combination with chrysin as a possible radiosensitizing agent in an MDA-MB-231 cell line as a model of a TNBC. The growth inhibitory effects of chrysin were examined using an MTT assay. Flow cytometry was performed to evaluate apoptosis and expression of hypoxia-induced factor-1α (HIF-1α). The protein expression of p-STAT3/STAT3 and Cyclin D1 was examined using western blotting. Real-time PCR determined apoptotic-related genes (Bax, BCL2, p53).. Treatment of MDA-MB-231 cells with chrysin in combination with RT caused synergistic antitumor effects, with an optimum combination index (CI) of 0.495. Our results indicated that chrysin synergistically potentiated RT-induced apoptosis in MDA-MB-231 compared with monotherapies (chrysin and/or RT alone). Expression of HIF-1α was decreased in the cells exposed to combinational therapy. The apoptotic effect of combinational therapy was correlated with increased Bax (pro-apoptotic gene) and p53 levels along with reduced expression of Bcl-2 (anti-apoptotic gene). Increased apoptosis was associated with reduced expression of Cyclin D1, p-STAT3.. These findings highlight the potential effect of chrysin as a radiosensitizer, indicating the synergistic anti-cancer effect of chrysin and RT in TNBC. Further investigation is warranted in this regard.

Topics: Apoptosis; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Humans; Triple Negative Breast Neoplasms; Tumor Suppressor Protein p53

Objective: To explore the possibility of a novel chemopreventive strategy for improving breast cancer treatment,\ the anticancer effects of a combination two natural compounds, Chrysin and Metformin, against T47D breast cancer\ cells were investigated. Materials and Methods: After treatment of T47D cells with Metformin, Chrysin and the two\ drugs in combination, toxicity to cancer cells was evaluated by MTT assay. Real time PCR was then used to determine\ the expression levels of hTERT and cyclin D1 genes. Results: The MTT test findings showed that the combination of\ metformin and chrysin had high synergistic effects in killing cancer cells. In addition PCR demonstrated a significant\ decrease in cyclin D1 and hTERT gene expression in the T47D breast cancer cell line. Conclusion: The conmbination\ of metformin and chrysin suppressing hTERT and cyclin D1 gene expression might offer an appropriate approach for\ breast cancer therapy.

Topics: Apoptosis; Breast Neoplasms; Cell Proliferation; Cyclin D1; Drug Combinations; Drug Synergism; Female; Flavonoids; Gene Expression Regulation, Neoplastic; Humans; Hypoglycemic Agents; Metformin; Telomerase; Tumor Cells, Cultured

Polymeric nanoparticles are attractive materials that have been widely used in medicine for drug delivery, with therapeutic applications. In our study, polymeric nanoparticles and the anticancer drug, chrysin, were encapsulated into poly (D, L-lactic-co-glycolic acid) poly (ethylene glycol) (PLGA-PEG) nanoparticles for local treatment.. PLGA: PEG triblock copolymers were synthesized by ring-opening polymerization of D, L-lactide and glycolide as an initiator. The bulk properties of these copolymers were characterized using 1H nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy. In addition, the resulting particles were characterized by scanning electron microscopy.. The chrysin encapsulation efficiency achieved for polymeric nanoparticles was 70% control of release kinetics. The cytotoxicity of different concentration of pure chrysin and chrysin loaded in PLGA-PEG (5-640μM) on T47-D breast cancer cell line was analyzed by MTT-assay.. There is potential for use of these nanoparticles for biomedical applications. Future work should include in vivo investigation of the targeting capability and effectiveness of these nanoparticles in the treatment of breast cancer.

Topics: Apoptosis; Blotting, Western; Breast Neoplasms; Cell Cycle; Cell Proliferation; Cyclin D1; Drug Carriers; Drug Delivery Systems; Female; Flavonoids; Humans; Lactic Acid; Nanoparticles; Polyethylene Glycols; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured