1.Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid.
Soriano-Hernandez AD1, Madrigal-Pérez D2, Galvan-Salazar HR1, Martinez-Fierro ML3, Valdez-Velazquez LL4, Espinoza-Gómez F2, Vazquez-Vuelvas OF4, Olmedo-Buenrostro BA2, Guzman-Esquivel J5, Rodriguez-Sanchez IP6, Lara-Esqueda A7, Montes-Galindo DA8, Delgado-Enciso I1. Oncol Lett. 2015 Oct;10(4):2574-2578. Epub 2015 Aug 7.
Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluated in vitro. Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10-40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50-90% of cell death corresponding to 100 µM).
2.Effect of N-Phenylanthranilic Acid Scaffold Nonsteroidal Anti-inflammatory Drugs on the Mitochondrial Permeability Transition.
Tatematsu Y1, Hayashi H, Taguchi R, Fujita H, Yamamoto A, Ohkura K. Biol Pharm Bull. 2016;39(2):278-84. doi: 10.1248/bpb.b15-00717.
Hepatotoxicity is a known side effect of nonsteroidal anti-inflammatory drugs (NSAIDs). In the present study, the effects of N-phenylanthranilic acid (NPA) scaffold NSAIDs on rat liver mitochondria were examined. Mefenamic acid (MEF, 200 µM) induced mitochondrial swelling, which was inorganic phosphate (Pi)-dependent and suppressed by cyclosporin A (CsA, 2.5 µM), similar to calcium-induced swelling. Mitochondrial swelling was also observed following the addition of 200 µM flufenamic acid (FLU), meclofenamic acid (MCL), and tolfenamic acid (TOL). Less swelling was observed with the addition of 200 µM diclofenac (DIC) or NPA. Diphenylamine (DPA)-induced swelling occurred in a Pi-independent manner and was not sensitive to CsA. The mechanism by which DPA interacted with the mitochondrial inner membrane differed from those of the other NPA scaffold NSAIDs. The addition of 50 µM MEF, MCL, TOL, and FLU had uncoupling effects in mitochondrial inner membrane.
3.Histological changes caused by meclofenamic acid in androgen-independent prostate cancer tumors: evaluation in a mouse model.
Delgado-Enciso I1,2, Soriano-Hernández AD1, Rodriguez-Hernandez A1, Galvan-Salazar HR1,2, Montes-Galindo DA1, Martinez-Martinez R1, Valdez-Velazquez LL3, Gonzalez-Alvarez R1, Espinoza-Gómez F1, Newton-Sanchez OA1, Lara-Esqueda A4, Guzman-Esquivel J1,5. Int Braz J Urol. 2015 Sep-Oct;41(5):1002-7. doi: 10.1590/S1677-5538.IBJU.2013.00186.
Meclofenamic acid is a nonsteroidal anti-inflammatory drug that has shown therapeutic potential for different types of cancers, including androgen-independent prostate neoplasms. The antitumor effect of diverse nonsteroidal anti-inflammatory drugs has been shown to be accompanied by histological and molecular changes that are responsible for this beneficial effect. The objective of the present work was to analyze the histological changes caused by meclofenamic acid in androgen-independent prostate cancer. Tumors were created in a nude mouse model using PC3 cancerous human cells. Meclofenamic acid (10 mg/kg/day; experimental group, n=5) or saline solution (control group, n=5) was administered intraperitoneally for twenty days. Histological analysis was then carried out on the tumors, describing changes in the cellular architecture, fibrosis, and quantification of cellular proliferation and tumor vasculature. Meclofenamic acid causes histological changes that indicate less tumor aggression (less hypercellularity, fewer atypical mitoses, and fewer nuclear polymorphisms), an increase in fibrosis, and reduced cellular proliferation and tumor vascularity.
4.Mefenamic acid in combination with ribavirin shows significant effects in reducing chikungunya virus infection in vitro and in vivo.
Rothan HA1, Bahrani H2, Abdulrahman AY3, Mohamed Z4, Teoh TC5, Othman S6, Rashid NN7, Rahman NA8, Yusof R9. Antiviral Res. 2016 Mar;127:50-6. doi: 10.1016/j.antiviral.2016.01.006. Epub 2016 Jan 18.
Chikungunya virus (CHIKV) infection is a persistent problem worldwide due to efficient adaptation of the viral vectors, Aedes aegypti and Aedes albopictus mosquitoes. Therefore, the absence of effective anti-CHIKV drugs to combat chikungunya outbreaks often leads to a significant impact on public health care. In this study, we investigated the antiviral activity of drugs that are used to alleviate infection symptoms, namely, the non-steroidal anti-inflammatory drugs (NSAIDs), on the premise that active compounds with potential antiviral and anti-inflammatory activities could be directly subjected for human use to treat CHIKV infections. Amongst the various NSAID compounds, Mefenamic acid (MEFE) and Meclofenamic acid (MECLO) showed considerable antiviral activity against viral replication individually or in combination with the common antiviral drug, Ribavirin (RIBA). The 50% effective concentration (EC50) was estimated to be 13 μM for MEFE, 18 μM for MECLO and 10 μM for RIBA, while MEFE + RIBA (1:1) exhibited an EC50 of 3 μM, and MECLO + RIBA (1:1) was 5 μM.