tolfenamic-acid and Neoplasms

Tolfenamic acid is one of the conventional non-steroidal anti-inflammatory drugs (NSAIDs) commonly used for the treatment of inflammation, migraines and pain. There has been a growing body of experimental evidence that tolfenamic acid possesses anti-cancer activity. However, in order to develop a therapeutic strategy using tolfenamic acid for the treatment of cancer, further research is required to highlight reliable cellular and molecular mechanisms of anti-cancer properties. Tolfenamic acid has been shown to alter the expression of several genes that represent cancer hallmarks including apoptosis, growth arrest, angiogenesis and metastasis. Recently, a couple of research groups including ours reported that tolfenamic acid targets multiple oncogenic or tumor suppressive signaling pathways in various types of cancer models. Here, we highlight multiple molecular targets responsible for the anti-cancer mechanism of tolfenamic acid and the benefits of combinational use of this drug with other anti-cancer drugs.

Topics: Animals; Antineoplastic Agents; Apoptosis; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; ortho-Aminobenzoates; Signal Transduction

The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Humans; Lipogenesis; Neoplasms; Oxidative Stress; Pentose Phosphate Pathway; Phosphogluconate Dehydrogenase; Protein Serine-Threonine Kinases; Ribulosephosphates; Signal Transduction

Non-steroidal anti-inflammatory drugs (NSAIDs) are used extensively for analgesic and antipyretic treatments. In addition, NSAIDs reduce the risk and mortality to several cancers. Their mechanisms in anti-tumorigenesis are not fully understood, but both cyclooxygenase (COX)-dependent and -independent pathways play a role. We and others have been interested in elucidating molecular targets of NSAID-induced apoptosis. In this review, we summarize updated literature regarding cellular and molecular targets modulated by NSAIDs. Among those NSAIDs, sulindac sulfide and tolfenamic acid are emphasized in this review because these two drugs have been well investigated for their anti-tumorigenic activity in many different types of cancer.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Humans; Neoplasms; ortho-Aminobenzoates; Prostaglandin-Endoperoxide Synthases; Sulindac

Non-steroidal anti-inflammatory drugs (NSAIDs) are primarily used for the treatment of acute or chronic conditions with pain and inflammation. Evidence from a wide range of sources suggested that chronic administration of NSAIDs reduced the risk of cancer incidences. Both the epidemiological and animal studies showed an inverse association between the incidence of various cancers and the use of aspirin or other NSAIDs. The chemopreventive and therapeutic interventions of NSAIDs in cancer are obvious; however, the instigation of drug and treatment period depends on the study objective. Typically, prevention involves initiating the medication before the appearance of clinical symptoms and lasts long-term; while treatment could be short-term and contingent to the response of patient to the medication. Recent studies from our laboratories provided substantial evidence on the anti-cancer activity of tolfenamic acid, a NSAID for the potential applications in pancreatic, esophageal and lung cancers. In this review, we provide a summary on the potential benefits of NSAIDs in a variety of human cancers with more emphasis on tolfenamic acid.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Proliferation; Humans; Mice; Neoplasms; ortho-Aminobenzoates; Radiation Tolerance; Sp Transcription Factors

The non-steroidal anti-inflammatory drug, Tolfenamic acid (TA) acts as an anti-cancer agent in several adult and pediatric cancer models. Copper (Cu) is an important element with multiple biological functions and has gained interest in medical applications. Recently, [Cu(TA)

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Apoptosis; Cell Proliferation; Copper; Humans; Neoplasms; ortho-Aminobenzoates; Tumor Cells, Cultured