Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid

Abstract

Abstract. 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). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug.

<p>Enhancing Anti-Tumor Activity of Sorafenib Mesoporous Silica Nanomatrix in Metastatic Breast Tumor and Hepatocellular Carcinoma via the Co-Administration with Flufenamic Acid</p>

“…FFA has slight to moderate toxicity (10-40% of cell death corresponding to 100 µM) in uterine cervical cancer cell lines. 58 The present study demonstrated that FFA had moderate anti-tumor activity (30-40% of cell death corresponding to 50 µg/mL) in 4T1/luc or HepG2 cells. FFA can also be used as a free radical scavenger and gap junction blocker in cancer cells.…”

Butein induces apoptotic cell death of human cervical cancer cells

“…In the context of its antitumor activity, butein is reported to downregulate metastatic protease and angiogenic factor expression of prostate cancer cells ( 41 ) and chemokine receptor expression and function of breast and pancreatic tumor cells ( 16 ), mainly through inactivating NF-κB signaling. Increasing evidence also supports the notion that anti-inflammatory drugs may also confer anti-neoplastic effect against uterine cervical cancer or HPV-dependent neoplasia ( 42 ). This raises the possibility that the combination strategy of using anti-inflammatory and conventional anti-tumor drugs may confer higher sensitivity to some types of tumors.…”

The m6A RNA Demethylase ALKBH5 Promotes Radioresistance and Invasion Capability of Glioma Stem Cells

“…Several RNA demethylases inhibitors have already been developed with a potent anticancer effect. More particularly, FTO inhibitors, meclofenamic acid (MA), or its ethyl ester form (MA2) have been recently identified as specific FTO inhibitors that have shown antitumor activity on myeloid leukemia (AML) and GBM, prostate, and uterine cervical cancers [ 12 , 53 , 54 , 55 , 56 ]. R-2-hydroxyglutarate (R-2HG), an oncometabolite resulting from the conversion of α-ketoglutarate by mutant IDH1/2 enzymes, has also been shown to specifically inhibit FTO and proliferation of leukemic or GBM cells [ 13 ].…”