chrysin and Triple-Negative-Breast-Neoplasms

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

New chrysin-De-allyl-Pac-1 hybrid analogues, tethered with variable heterocyclic systems (

Topics: Allyl Compounds; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Movement; Cell Proliferation; Female; Flavonoids; Humans; Hydrazones; Piperazines; Triple Negative Breast Neoplasms; Tumor Cells, Cultured

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Female; Flavonoids; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Receptors, Estrogen; Receptors, G-Protein-Coupled; Triple Negative Breast Neoplasms; Up-Regulation; Xenograft Model Antitumor Assays

Triple-negative breast cancer (TNBC) is difficult to treat because there is no targeted therapy available. Clinical studies have demonstrated that S-phase kinase-associated protein 2 (Skp2) and low-density lipoprotein receptor-related protein 6 (LRP6) are highly expressed in TNBC. Therefore, therapeutic strategies designed to downregulate LRP6 or Skp2 may play an important clinical role in the treatment of TNBC. However, the regulatory effects of many drugs on Skp2 and LRP6 expression are currently unknown. In the present study, combined treatment with chrysin and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (5GG) synergistically induced apoptosis and cell cycle arrest and inhibited cell proliferation and colony formation in AU565 and MDA-MB-231 human breast cancer cells. Furthermore, the combination of chrysin and 5GG suppressed tumor growth in nude mice with xenografted MDA-MB-231 cells by downregulating the phospho-LRP6 (pLRP6) and Skp2 proteins. Overall, our findings suggested that the combination of chrysin and 5GG has a potential therapeutic value in treating breast cancer, particularly for TNBC associated with Skp2/LRP6 overexpression, and hence warrants further investigation.

Topics: Animals; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Drug Synergism; Female; Flavonoids; Heterografts; Humans; Hydrolyzable Tannins; Low Density Lipoprotein Receptor-Related Protein-6; Mice, Inbred BALB C; Mice, Nude; S-Phase Kinase-Associated Proteins; Triple Negative Breast Neoplasms

Chrysin, a naturally occurring flavone, has been shown to inhibit cell proliferation and induce cell apoptosis in various cancers. However, the effect and mechanisms of chrysin on cancer metastasis are still enigmatic. In this study, metastatic triple-negative breast cancer (TNBC) cell lines were used to evaluate the antimetastatic activity of chrysin. The results showed that chrysin (5, 10 and 20 μM) significantly suppressed TNBC cell migration and invasion in a dose-dependent manner. Human matrix metalloproteinase (MMP) antibody array demonstrated that MMP-10 was downregulated by chrysin, which was further verified by Western blotting and ELISA. Moreover, it was shown that chrysin induced increased E-cadherin expression and decreased expression of vimentin, snail and slug in TNBC cells, suggesting that chrysin had a reversal effect on epithelial-mesenchymal transition. More importantly, it was demonstrated that inhibiting the Akt signal pathway might play a central role in chrysin-induced antimetastatic activity by regulating MMP-10 and epithelial-mesenchymal transition. In conclusion, our study indicates that chrysin exerts antimetastatic activities in TNBC cells, which suggests that chrysin might be a potential therapeutic candidate for the treatment of advanced or metastatic breast cancer.

Topics: Antigens, CD; Antineoplastic Agents; Cadherins; Cell Line, Tumor; Cell Movement; Cell Survival; Down-Regulation; Epithelial-Mesenchymal Transition; Female; Flavonoids; Humans; Matrix Metalloproteinase 10; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Triple Negative Breast Neoplasms; Vimentin; Wound Healing