Synergistic Anticancer Effects of Nano-encapsulated Artemisinin-Chrysin on hTERT gene expression in human Breast Cancer T۴۷D Cell line

Background and Aim: Cancer is a major public health problem worldwide and Breast cancer is one of the most significant causes of female cancer death worldwide. Despite the development of newer diagnostic methods, breast cancer recurrence, metastasis and drug resistance are still the major problems for breast cancer. Molecular targeted therapies are revolutionized therapeutics which interfere with specific molecules to block cancer growth, progression and metastasis. hTERT is usually silenced in almost all somatic cells but it is significantly expressed in ~۹۰ % of human cancers. Therefore telomerase is a known global therapeutic target in cancer cells. To explore the possibility of a novel chemopreventive strategy for improving breast cancer treatment, the anticancer effects of a combination two natural compounds, Artemisinin (Art) and Chrysin (Chr), against T۴۷D breast cancer cells were investigated.Methods: For this purpose, Artemisinin and Chrysin were co-encapsulated in PEGylated PLGA nanoparticles (NPs) and evaluated for their therapeutic efficacy. The morphology and dynamic light scattering (DLS) analyses were carried out to optimize the Nano formulations. The FT-IR and SEM method has also been used for further analysis. Drug release study was performed using dialysis method and then the cytotoxic and inhibitory effect of individual and combined drugs on expression level of hTERT in T۴۷D breast cell line were evaluated using MTT assay and qPCR, respectively.Results: The results showed that free drugs and formulations exhibited dose-dependent cytotoxicity against T۴۷D cells and especially, Art–Chr–PLGA/PEG NPs had more synergistic anti-proliferative effect and significantly arrested the growth of cancer cells than the other groups. Real-time PCR results revealed that Art, Chr and combination of Art–Chr in free and encapsulated forms inhibited hTERT gene expression. It was found that Art–Chr–PLGA/PEG NPs in relative to free combination could further decline hTERT expression in all concentration.Conclusion: Our study demonstrated that Art–Chr–PLGA/PEG NPs based combinational therapy holds promising potential towards the treatment of breast cancer.

Keywords:

Breast cancer , Artemisinin , Chrysin , hTERT , Nano-encapsulated , Target therapy