Clustered regularly interspaced short palindromic repeats/CRISPR‐associated nuclease 9 (CRISPR‐Cas9) is an RNA‐guided gene editing tool which offers several advantageous characteristics in comparison with the conventional methods (e.g., zinc finger nucleases and transcription activator‐like effector nucleases) such as cost‐effectiveness, flexibility, and being easy‐to‐use. Despite some limitations such as efficient delivery and safety, CRISPR‐Cas9 is still the most convenient tool for gene editing purposes. Due to the potential capability of the CRISPR‐Cas9 system in genome editing and correction of casual mutations, it can be considered as a possible therapeutic system in the treatment of disorders associated with the genome mutations and in particular cancer treatment. In this review, we will discuss CRISPR‐Cas‐based gene editing along with its classifications and mechanism of action. Furthermore, the therapeutic application of the CRISPR‐Cas9 system in mutational disorders, delivery systems, as well as its advantages and limitations with a special emphasis on cancer treatment will be discussed.
The study was aimed at investigating the synergistic inhibitory effect of unique combinational regimen of nanocapsulated Metformin (Met) and Curcumin (Cur) against T47D breast cancer cells. For this purpose, Met and Cur 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 nanoformulations. 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 T47D breast cell line were evaluated using MTT assay and qPCR, respectively. The results showed that free drugs and formulations exhibited a dose-dependent cytotoxicity against T47D cells and especially, Met-Cur-PLGA/PEG NPs had more synergistic antiproliferative effect and significantly arrested the growth of cancer cells than the other groups (p < .05). Real-time PCR results revealed that Cur, Met and combination of Met-Cur in free and encapsulated forms inhibited hTERT gene expression. It was found that Met-Cur-PLGA/PEG NPs in relative to free combination could further decline hTERT expression in all concentration (p < .05). Taken together, our study demonstrated that Met-Cur-PLGA/PEG NPs based combinational therapy holds promising potential towards the treatment of breast cancer.
Globally at 2014, it was estimated that there was 347 million people with diabetes in which 90 percent of them were diagnosed with type 2 diabetes mellitus (T2DM). Although the association between diabetes mellitus and cancer risk was found about 100 years ago, the issue is not still clear. Many studies especially cohort and case-control studies have suggested a higher risk of cancer in patients with diabetes mainly in those with type 2 diabetes. Insulin concentration is high in these patients, and due to its mitogenic effects, it may be a possible hypotheses for higher risk of cancer in diabetic patients. Therefore, antidiabetic drugs, which are involved in insulin secretion and sensitivity, may have beneficial effects in cancer treatment. Several groups of drugs with different mechanisms of action, mostly prescribed orally, are used for the treatment of type 2 diabetes mellitus including, insulin sensitizers (thiazolidinediones), insulin secretagogues (sulfonylureas), and biguanides. In this review, the possible effects of antidiabetic drugs (biguanides, thiazolidinediones, and sulfonylureas) and some of their mechanisms for overcoming cancer will be discussed.
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