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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. [ABSTRACT FROM AUTHOR]

Background: Biological activities of Zanthoxylum rhetsa have been well studied, and its various parts have been reported to possess anticancer activities. The reports on anticancer activities of proteins from the fruits of Z. rhetsa are limited. Objectives: The study assessed the proapoptotic and antiangiogenic activity of partially purified proteins from the pericarp of Z. rhetsa. Methods: MCF-7, MDA MB 231, HeLa, and HCT 116 cells treated with partially purified protein fractions of Z. rhetsa pericarp were assessed for cytotoxicity by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-diphenyl tetrazolium bromide (MTT) assay. Fraction ZR3 showed high cytotoxicity against the MCF-7 cells; hence, it was chosen for further assays. The proapoptotic activity was scrutinized by Giemsa staining, acridine orange-ethidium bromide staining, and DNA fragmentation assay. The study was supported by wound healing assay and colony formation assay. Cell cycle analysis was performed by fluorescence-activated cell sorter. Ehrlich ascitic carcinoma-bearing Swiss albino mice were used as in vivo model. Angiogenesis was studied by peritoneal angiogenesis in mice and chorioallantoic membrane assay in fertilized eggs. Results: MTT assay showed the inhibition of MCF-7 cells (IC50 = 21.5 µg/mL) by ZR3 fraction. Reduction in proliferation and failure to produce large cell colonies were observed. Proapoptotic activity was evident from the DNA fragmentation and staining methods. ZR3 blocked the cells in the G2/M phase of the cell cycle. In vivo studies suggested the antiproliferative and proapoptotic activities of ZR3. ZR3 exhibited antiangiogenic properties in vivo. Conclusion: This study confirmed the role of Z. rhetsa partially purified proteins as a potential proapoptotic and antiangiogenic agent against the MCF-7 cell line. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Pundalik et al.)