METHODOLOGY AND USE BASED ON NEXT-GENERATION ULTRASOUND CURCUMIN (NGUC) APPLICATION IN PANCREATIC ADENOCARCINOMA CELLS

Abstract

The invention relates to a method for suppressing cell proliferation and inhibiting the NF-κB signaling pathway, which plays a critical role in tumor progression, by applying Next Generation Ultrasol Curcumin (NGUC), a curcumin formulation with increased bioavailability, to pancreatic cancer cells, and to an in vitro application involving the application of NGUC to a pancreatic adenocarcinoma cell line at specific concentrations and time intervals. Within this application, cell viability and NF-κB protein expression levels are determined.

Description

1 TARIFF NEW GENERATION ULTRASOL IN PANCREATIC ADENOCARCINOMA CELLS METHOD AND USE BASED ON CURCUMIN (NGUC) APPLICATION TECHNICAL AREA 5 The invention is in the technical fields of biotechnology, molecular biology, and oncology; Curcumin with increased bioavailability, especially in pancreatic cancer cells. Suppression of cellular proliferation through the use of formulations and This relates to a method and its application for inhibiting the NF-κB signaling pathway. STATE OF THE ART Pancreatic cancer is characterized by its aggressive clinical course and resistance to chemotherapeutic agents. treatment success rates are low due to the potential for developing high resistance. These are malignancies. In current clinical practice, chemotherapy regimens are widely used. It is currently in use, but due to its high side effect profile and limited survival advantage, 15 Treatment efficacy is not reaching the desired level. Therefore, pancreatic... Targeted therapies for cancer, inflammation and cellular proliferation Extensive research is being conducted on agents that suppress these processes. NF-κB is involved in chemotherapy resistance, proliferation, metastasis, and in pancreatic cancer. It is one of the key regulatory signaling pathways associated with inflammation. Therefore, 20 NF-κB inhibitors are an important therapeutic target in the preclinical field. It is being evaluated. Currently, some small molecule inhibitors and natural... Derived compounds are under investigation for suppressing NF-κB; however There is no effective agent that has received clinical approval. Furthermore, due to the low selectivity of the currently available agents, healthy 25 Toxic effects can also be seen in cells; this can affect the quality of life of patients. This leads to a decline in treatment adherence and decreased compliance. In conclusion, compared to the previous technique; - Limited therapeutic effect due to low bioavailability, - Inability to effectively suppress the NF-κB signaling pathway, 30 - Resistance to chemotherapy, - High side effect profile and normal cell toxicity, - There are significant technical issues, such as limited contribution to survival. 2 Plant-derived polyphenolic compounds have a low toxicity profile and multiple effects. Due to its properties, curcumin is attracting attention in cancer research. Widely used due to its antioxidant, anti-inflammatory and antiproliferative effects. It has potential. However, low bioavailability is a major limiting factor in clinical efficacy. This has been identified as a problem. Various nano-carriers have been developed to overcome this problem. 5 Although formulations based on liposomal and micellar substances have been developed, However, efforts to increase its effectiveness are ongoing. Next Generation Ultrasol Curcumin (NGUC) improves the bioavailability of curcumin. It is an innovative formulation developed to improve gastrointestinal function. The aim was to increase the stability of the system. However, NGUC's pancreatic 10 its use in cancer-specific treatment, its effect on NF-κB-mediated mechanisms, and The cytotoxic response profile is not described in the literature. In this context, in the previous technique... The following technical problems were found to exist simultaneously:  Due to the low bioavailability of curcumin, sufficient therapeutic efficacy is not achieved. failure to provide, 15  The inability to effectively and selectively inhibit the NF-κB signaling pathway,  Resistance to chemotherapy developing in pancreatic cancer cells inability to overcome these mechanisms,  Current treatments have high toxicity and target healthy cells. damage, 20  Insufficient treatment approaches that provide targeted and controlled effects. being. Consequently, by using a curcumin formulation with increased bioavailability In pancreatic cancer cells, it both suppresses cell proliferation and... by directly inhibiting the NF-κB signaling pathway, thus enabling chemotherapy 25 a treatment that reduces resistance and offers high therapeutic efficacy with lower toxicity Developing a new methodology is extremely important. A BRIEF DESCRIPTION OF THE INVENTION The invention describes a curcumin 30 with increased bioavailability in pancreatic cancer cells. By applying Next Generation Ultrasol Curcumin (NGUC), which is a formulation, suppression of cell proliferation and plays a critical role in tumor progression. A method and its application that enables the inhibition of the NF-κB signaling pathway. It is related. 3 Within the scope of the invention, NGUC's pancreatic adenocarcinoma cell line (PSN- 1) Cell viability through application under specific dose and duration parameters. and protein expression levels are analyzed; according to the results obtained NGUC reduces cell viability in a dose- and time-dependent manner, and NF-κB It has been shown to significantly suppress protein expression. 5 Our discovery addresses the low bioavailability of classic curcumin formulations. by providing a technical solution to the problem, achieving an effective concentration in target cells. It offers an accessible application. In this way, both in pancreatic cancer Cytotoxic effects are created at the cellular level, as well as chemotherapy resistance. The directly related NF-κB signaling pathway is suppressed. 10 Our invention allows for not only the use of a single compound, but also a specific concentration. intervals, application times and measurable biological outputs (cell viability and defined by protein expression, which is technically verifiable and reproducible. It presents a new method. In this respect, our invention differs from the previous technique. as a treatment optimized at both the pharmacokinetic and molecular levels 15 Our invention offers significant technical and therapeutic advantages. These provide: 1. Increased bioavailability and effective concentration. The NGUC formulation ensures the stability and absorption of curcumin in the gastrointestinal system. By increasing it, it provides higher bioavailability in target cells. This situation is different from the classic 20 Eliminating the problem of low efficacy observed in curcumin formulations. This allows for significant biological effects to be achieved even at lower doses. He recognizes. 2. Dose- and time-dependent controlled cytotoxic effect. Experimental data obtained within the scope of the invention show that NGUC maintains cell viability for a specific 25 days. controllable within concentration ranges and application times This shows that it reduces [the effects of treatment]. This situation leads to the optimization of treatment protocols and It allows for targeted dose adjustments. 3. Direct inhibition of the NF-κB signaling pathway. One of the most important technical contributions of the invention is that it reduces the progression of pancreatic cancer by 30 It is the direct suppression of the NF-κB signaling pathway, which plays a critical role. NGUC Significant reduction in NF-κB protein expression with this application, tumor mechanisms of cell proliferation, invasion and chemotherapy resistance It helps to weaken it. 4 4. Low toxicity and high selectivity. Because it is based on natural compounds, NGUC is an alternative to classical chemotherapeutic agents. It has a lower toxicity potential in comparison. This means that healthy cells It helps protect against disease while reducing treatment-related side effects. 5. Bidirectional mechanism of action 5 The invention explores both the cytotoxic effect, which directly reduces cell viability, and the molecular effect. By simultaneously providing signal pathway inhibition at this level, it creates a bidirectional effect. This provides a mechanism. This situation is an important factor in increasing treatment effectiveness. This creates an advantage. LIST OF FIGURES Figure 1. PSN-1 cell line at 24, 48, and 72 hours after NGUC administration. subsequent cell survival rates (percentage) Figure 2. Effect of NGUC application on NF-1 in PSN-1 pancreatic cancer cell line. Effect on κB protein levels (a) % ratio (b) Western blot comparison 15 appearance DETAILED DESCRIPTION OF THE INVENTION The invention involves increasing bioavailability in pancreatic cancer cells. By applying Next Generation Ultrasol Curcumin (NGUC), a curcumin formulation, 20 Cellular responses are being analyzed. NGUC; standardized 95% curcuminoid isopropyl extract along with phospholipids, monoglycerides and acidifying components a curcumin-based mixture prepared by mixing in alcohol at 55–60 °C It can be defined as a formulation. After the resulting mixture is cooled to 40 °C... Then, hypromellose, medium-chain triglyceride oil, and tocopherol are added to achieve a homogeneous structure. 25 provided; then spray drying and vacuum drying processes were applied. A yellowish-orange, free-flowing, homogeneous powder product was obtained. The NGUC formulation contains approximately 20% curcuminoid by weight. The invention is realized as a method involving the following steps: Step 1: Preparing the cell line 30 SN-1 human pancreatic adenocarcinoma cell line in suitable culture medium It is reproduced. Step 2: NGUC application To the cells;  In concentrations ranging from 283.6 µM to 640 µM  For periods of 24, 48 and 72 hours NGUC is administered. Thus, at these concentrations, NGUC exhibits strong cytotoxic activity. This has shown that NGUC has high anticancer potential in pancreatic cancer. This shows that it has potential. 5 Step 3: Measuring cell viability Cell viability after application is assessed using appropriate cell viability analysis methods. It is determined. According to the results obtained:  Cell viability decreased in a dose- and time-dependent manner. 10  Half-maximum inhibitory concentration (IC50) values ​​are as follows: - 24 hours → 310.3 µM - 48 hours → 304.9 µM - 72 hours → 283.6 µM It is determined that all groups are assigned their corresponding negative control with 15 compared (Figure 1). Step 4: Protein expression analysis NF-κB protein levels in NGUC-treated cells were analyzed using the Western blot method. It is done. In conclusion: 20  NF-κB expression was significantly reduced compared to the control group.  This reduction has a tumor progression suppressive effect. This is detected. Therefore, NF-κB inhibition by NGUC inhibits both tumor growth. a valuable tool that can both suppress and improve the effectiveness of existing treatments It offers a mechanism. 25 In an application example; 300 µM NGUC was applied to the SN-1 cell line, and after 48 hours the cells... A decrease of more than 50% in viability was observed in the same sample. NF-κB protein A significant suppression of its expression was detected.

Claims

6 REQUESTS 1. Suppression of cell proliferation in pancreatic cancer cells and It is a method aimed at inhibiting the NF-κB signaling pathway, and its characteristic feature is; - pancreatic adenocarcinoma cell line in culture medium 5 preparation, - Curcumin with increased bioavailability to the cell line in question Next Generation Ultrasol Curcumin (NGUC), a formulation with a concentration of 283.6 µM Application at concentrations ranging from 640 µM, - NGUC's 10 cells for periods ranging from 24 to 72 hours. making contact, - subsequently determining cell viability, - Analysis of NF-κB protein expression levels It is characterized by including its steps.

2. Next Generation Ultrasol 15, a curcumin formulation with enhanced bioavailability. Curcumin (NGUC) and NF-κB protein expression levels It has been determined for in vitro use and its characteristic feature is; pancreatic adenocarcinoma cells in the line at concentrations ranging from 283.6 µM to 640 µM and 24 It is characterized by being applied for periods ranging from 7 to 72 hours.

3. The method is based on Claim 1 and its characteristic feature is that the cell line is SN-1 human pancreatic 20 It is characterized by being an adenocarcinoma cell line.

4. This method, according to claim 1, is characterized by its ability to maintain cell viability through dose and time. It is characterized by the determination that it decreases in a dependent manner.

5. This method is based on Claim 1 and its characteristic feature is that cell viability is at half maximum. The inhibitory concentration (IC50) value should be 25. - 310.3 µM for 24 hours, - 304.9 µM for 48 hours, - 283.6 µM for 72 hours It is characterized by being determined within a certain range.

6. This method, according to claim 1, is characterized by its ability to produce NF-κB 30 as a result of NGUC implementation. It is characterized by a decrease in protein expression compared to the control group.

7. It is a method according to claim 1, and its characteristic is that the method in question is a cell. It is characterized by its cytotoxic effect, which suppresses proliferation.

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