Synergistic Antiproliferative Effects of Co-nanoencapsulated Curcumin and Chrysin on MDA-MB-231 Breast Cancer Cells Through Upregulating miR-132 and miR-502c.

In this study, we explored whether co-nanoencapsulated Curcumin (Cur) and Chrysin (Chr), natural herbal compounds with antitumor activities, regulate miR-132 and miR-502c and their downstream targets, leading to the synergistic growth inhibition in MDA-MB-231 breast cancer cells. For this purpose, Cur and Chr were co-encapsulated into PLGA-PEG nanoparticles (NPs) and characterized through DLS, FTIR and FE-SEM. MTT assay and cell cycle arrest analysis revealed that CurChr-loaded NPs had a considerable synergistic cytotoxicity against MDA-MB-231 cells with more cell accumulation in G2/M phase compared to the other groups. In addition, highest percentage of cell apoptosis was acquired in cells treated with CurChr-loaded NPs according to apoptosis analysis. Real-time PCR findings revealed that co-encapsulated form of Cur and Chr than free combination could further upregulate miR-132 and miR-502c expression (P < 0.001). Also, the strong reduction was detected in the protein levels of HN1 and P65 at the cells co-nanodelivered with Cur and Chr. These findings demonstrated that the co-nanodelivery of Cur and Chr through targeting miR-132 and miR-205c might be a novel strategy for the treatment of breast cancer.

Leukemia therapy by flavonoids: Future and involved mechanisms.

Flavonoids are a varied family of phytonutrients (plant chemicals) usually are detected in fruits and vegetables. In this big family, there exist more than 10,000 members that is separated into six chief subtypes: isoflavonols, flavonoenes, flavones, flavonols, anthocyanins, and chalcones. The natural compounds, such as fruits, have visible positive effects in regulating of survival involved signaling pathways that performance as the regulator of cell survival, growth, and proliferation. Researchers have established that commonly consumption up flavonoids decreases incidence and development risk of certain cancers, especially leukemia. Flavonoids have been able to induce apoptosis and stimulate cell cycle arrest in cancer cells via different pathways. Similarly, they have antiangiogenesis and antimetastasis capability, which were shown in wide ranges of cancer cells, particularly, leukemia. It seems that flavonoid because of their widespread approval, evident safety and low rate of side effects, have hopeful anticarcinogenic potential for leukemia therapy. Based on the last decade reports, the most important acting mechanisms of these natural compounds in leukemia cells are stimulating of apoptosis pathways by upregulation of caspase 3, 8, 9 and poly ADP-ribose polymerase (PARP) and proapoptotic proteins, particularly Bax activation. As well, they can induce cell cycle arrest in target cells not only via increasing of activated levels of p21 and p53 but also by inhibition of cyclins and cyclin-dependent kinases. Furthermore, attenuation of neclear factor-κB and signal transducer and activator of transcription 3 activation, suppression of signaling pathway and downregulation of intracellular antiapoptotic proteins are other significant antileukemic function mechanism of flavonoids. Overall, it appears that flavonoids are promising and effective compounds in the field of leukemia therapy. In this review, we tried to accumulate and revise most promising flavonoids and finally declared their major working mechanisms in leukemia cells.