RESUMEN
Background: Inflammation is generally connected to tumour progression and development. The secretory phospholipase A2IIa (sPLA2IIa) is an important inflammatory enzyme that catalyse the hydrolysis of membrane phospholipids into arachidonic and lysophosphatidic acid, which are the precursors for production of a lot of pro-inflammatory mediators like prostaglandins, prostacyclins, thromboxanes, leukotrienes and platelet activating factors, which involved in the proliferation, migration, invasion, and metastasis. Therefore, investigating safe and effective sPLA2IIa inhibitors as a therapeutic agent to treat cancer is indeed in need. Methods: Anti-inflammatory function of corosolic acid was evaluated by docking it with sPLA2IIa enzyme, sPLA2IIa inhibition, calcium and substrate concentration-dependent assays; intrinsic fluorescence and UV-CD analysis; neutralisation of sPLA2IIa induced indirect hemolytic and edema. Evaluated the anticancer activity of corosolic acid by MTT assays and caspase-3 expression; the anti-tumour activity by EAC-induced cell line and interleukin 6 expression. Results: The corosolic acid inhibits sPLA2IIa activity to 82.21±2.82%. The inhibition was evaluated by increasing calcium from 2.5 to 15 µM and substrate from 20 to 120 nM, it did not affect the level of inhibition. Corosolic acid altered the intrinsic fluorescence and UV-CD spectra of sPLA2IIa enzyme, indicating the direct interaction. It neutralised sPLA2IIa induced hemolytic activity from 97±1.23% to 15.75±1.44% and edema from 171.51±2.39% to 119.3±2.6%. Further, as antiproliferative activity, corosolic acid reduced the PC3 cell viability from 99.66±0.57% to 23±2.64% and suppressed LPS-induced IL-6 level from 94.35±2.2% to 34.36±2.4%. It increased mean survivability time from 30 to 38 days and displayed the drug-like qualities. Conclusion: All the experimental results have proven the corosolic acid as an anti-inflammatory and anticancer molecule that may further be used to develop it as a drug.
RESUMEN
PURPOSE: This study aims to compare hematological and biochemical profile changes in pre- and post-chemotherapy among cancer patients admitted at the Oncology Unit of Ayder Comprehensive Specialized Hospital (ACSH), Mekelle, Northern Ethiopia. PATIENTS AND METHODS: A retrospective cohort study was conducted in 376 cancer patients admitted in the Oncology Unit at ACSH. Demographic data, hematological and biochemical profiles were collected from smart care and patient cards. The data were analyzed using SPSS version 20 statistical package. Descriptive statistics and paired sample students T-test statistical methods were used. RESULTS: From 376 study subjects, 228 (60.6%) were females. All the hematological profiles, except lymphocyte (LYM) (P > 0.05), showed significant decrement in post-chemotherapy compared to pre-chemotherapy; white blood cell (WBC) (P < 0.01), red blood cell (RBC) (P < 0.01), hemoglobin (Hb) (P<0.001), hematocrit (HCT) (P < 0.05), platelet (PLT) (P < 0.001) and neutrophil (NUT) (P < 0.05). The biochemical profiles showed that blood urea nitrogen and creatinine levels were non-significantly decreased, urea (P > 0.05) and creatinine (CR) (P > 0.05), in post-chemotherapy compared to pre-chemotherapy whereas alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were non significantly increased, ALT (P > 0.05) and AST (P> 0. 05), in post-chemotherapy compared to pre-chemotherapy. CONCLUSION: Hematological profiles, except lymphocytes, were found significantly decreased whereas biochemical profiles, urea, and creatinine were decreased non-significantly, while AST and ALT showed non-significant increments in post-chemotherapy compared to pre-chemotherapy.