Therapeutic properties of Isoliquiritigenin with molecular modeling studies: Investigation of anti-pancreatic acinar cell tumor and as HMG-CoA reductase inhibitor for treatment of hypercholesterolemia

IntroductionIsoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have an anti-tumor activity in vitro and in vivo. HMG-CoA reductase inhibitors, called statins, are used to reduce the risk of heart disease by lowering blood cholesterol levels.Material and methodsHMG-CoA Reductase activity according to the method described by Takahashi S. et al. The structure of human HMG-COA reductase in the resolution of 2.22 Å with X-RAY diffraction method (PDB ID: 1HWK) was obtained from the PDB database.ResultsIn our study, inhibition result of Isoliquiritigenin on HMG-CoA reductase showed lower value IC50 = 193.77±14.85 µg / mL. For a better understanding of biological activities and interactions, the molecular docking study was accomplished. The results of molecular docking revealed that isoliquiritigenin with a docking score of -6.740 has a strong binding affinity to the HMG-COA reductase. Therefore, this compound could be considered as a potential inhibitor for the enzyme. Also, the properties of Isoliquiritigenin against common human pancreatic acinar cell tumor cell lines i.e. 266-6, TGP49, and TGP47 were evaluated.ConclusionsThe treated cells with Isoliquiritigenin were assessed by MTT assay for 48h about the cytotoxicity and anti-human pancreatic acinar cell tumor properties on normal (HUVEC) and human pancreatic acinar cell tumor cell lines i.e. 266-6, TGP49, and TGP47. The IC50 of Isoliquiritigenin were 262, 389, and 211 µg/mL against 266-6, TGP49, and TGP47 cell lines, respectively.

Survival Outcome and Prognostic Factors for Pancreatic Acinar Cell Carcinoma: Retrospective Analysis from the German Cancer Registry Group

Background: Pancreatic acinar cell carcinoma (PACC) is a distinct type of pancreatic cancer with low prevalence. We aimed to analyze prognostic factors and survival outcome for PACC in comparison to pancreatic ductal adenocarcinoma (PDAC), based on data from the German Cancer Registry Group. Methods: Patients with PACC and PDAC were extracted from pooled data of the German clinical cancer registries (years 2000 to 2019). The distribution of demographic parameters, tumor stage and therapy modes were compared between PACC and PDAC. The Kaplan–Meier method and Cox regression analysis were used to delineate prognostic factors for PACC. Propensity score matching was used to compare survival between PACC and PDAC. Results: There were 233 (0.44%) patients with PACC out of 52,518 patients with pancreatic malignancy. Compared to PDAC, patients with PACC were younger (median age 66 versus 70, respectively, p < 0.001) and the percentage of males was higher (66.1% versus 53.3%, respectively, p < 0.001). More patients were resected with PACC than with PDAC (56.2% versus 38.9%, respectively, p < 0.001). The estimated overall median survival in PACC was 22 months (95% confidence interval 15 to 27), compared to 12 months (95% confidence interval 10 to 13) in the matched PDAC cohort (p < 0.001). Surgical resection was the strongest positive prognostic factor for PACC after adjusting for sex, age, and distant metastases (hazard ratio 0.34, 95% confidence interval 0.22 to 0.51, p < 0.001). There was no survival benefit for adjuvant therapy in PACC. Conclusions: PACC has overall better prognosis than PDAC. Surgical resection is the best therapeutic strategy for PACC and should be advocated even in advanced tumor stages.