Investigation of the effect of PLGA-curcumin nano- formulation on the p65 sub-unit level of NF-kBb in cancer cell lines

In addition to the toxic effects of cancer chemotherapy agents on healthy cells, it is important to increase the effectiveness of these drugs with pro-oxidant polyphenols, especially considering the high cost of these drugs in clinical use. Although traditional cytotoxic chemotherapy remains the treatment of choice for many types of cancer, a dramatic change has occurred in cancer treatment in recent years. Great efforts have been made to design new drugs that will act more selectively for cancer cells and thus prevent unwanted side effects on normal cells and cause less side effects. With the use of polymeric nanoparticles as drug carriers, which has become an increasingly important approach in recent years, less systemic side effects are seen, higher drug concentrations are achieved in tumor tissue and the treatment efficiency is significantly increased. Polylactic-co-glycolic acid (PLGA), which is the most commonly used polymeric material, is a biomaterial that is inert, biodegradable, biocompatible in physiological environment, and is widely used in new drug delivery systems and has been approved by the FDA due to its ability to break down into non-toxic products. In many studies, the pharmacokinetics, safety and efficacy of curcumin, which is one of the leading polyphenols with prooxidant effect, have been revealed. Recently, anticancer activity of curcumin has been demonstrated and its preventive and therapeutic potential in cancer treatment has been emphasized. However, the use of this compound at high concentrations in biological activity tests is faced with problems due to its low solubility in water. NF-kB (Nuclear Factor Kappa B); It is a transcription factor that is an important regulator of many genes responsible for inflammation, immune response, proliferation and apoptosis. NF-kB is found inactive in the cytoplasm in all cells. NF-kB was identified by Ranjan Sen and David Baltimore in 1986 as a factor that binds to the enhancer region of the immunoglobulin kappa light chain gene in the nuclei of B lymphocytes. The NF-kB protein complex consists of five different sub-proteins (NF-kB1 (p50 / p105), NF-kB2 (p52 / p100), RelA (p65), RelB and c-Rel). NF-kB is necessary for the normal functioning of the immune system. It is stated that NF-kB is effective in the development of tumor cells and if NF-kB inhibition occurs, it makes the tumor cells sensitive to chemotherapy. The activation of NF-kB takes place with many different factors such as intracellular growth factors, oxidative stress, mitogens, pro-18 inflammatory cytokines, viruses, gram-negative bacteria products, environmental stress conditions. NF-kB is in a complex with the inhibitory protein IkB in the cell cytoplasm. By phosphorylation of the IkB protein by the IkB kinase complex (IKK), this protein is inactivated and separated from NF-kB. Thus, the released NF-KB passes into the nucleus. It leads to the activation of specific genes by binding to DNA. It was first demonstrated in 1995 by Singh and Aggarwal that curcumin has anti-inflammatory activity and provides its effect by suppressing NF-kB activation. Following the publication of this finding, studies conducted by other researchers have shown that it can inhibit other molecules in the NF-kB signaling pathway. It has been reported by many researchers that curcumin has an anti-cancer effect on many cancer cells such as pancreatic, breast, colorectal, oral, head-neck, glioblastoma, ovarian, prostate and T-cell lymphoma through inhibition of the NF-kB pathway. Many studies have proven the safety and effectiveness of curcumin in cancer treatment by preventing cancer development. It is thought that elucidating the structure and mechanism of NF-kB will play an important role in reducing cellular stress and eliminating the negative effects of stress with new perspectives. In the literature reviews, there is no study investigating the effect of PLGA-curcumin nanoformulation on the p65 subunit level of Nf-kB in cancer cells lines. Based on this point, our study aimed to examine the effect of PLGA-curcumin nanoformulation on the p65 subunit level of Nf-kB in cancer cells, with the thought that curcumin nanoformulation, which has been shown to have anticancer activity and emphasized its preventive and therapeutic potential in cancer treatment, can also be illuminating for NF-kB signaling mechanism. The effect of PLGA-Curcumin nano-formulation on the ratios of p65, was investigated on MDA-MB-231 breast cancer cells treated with paclitaxel. Although P65 is the unit most suppressed by PLGA-Curcumin, inhibition of inflammation in cancer cells with this nanoformulation increases the reliability of nanoformulations. Keywords: NF-kB, nano-formulation, curcumin, PLGA