Osteoarthritis of the Knee Treated with Tolfenamic Acid

Zachariae, E; Sylvest, Jesper

doi:10.3109/03009747209103005

Cited by 12 publications

(6 citation statements)

References 5 publications

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“…GAPDH, glyceraldehyde 3-phosphate dehydrogenase. (Zachariae and Sylvest, 1972;Rejholec et al, 1979;Wankya et al, 1981). Recent studies showed that Tol suppresses the cell growth and angiogenesis in pancreatic and colorectal cancer (Abdelrahim et al, 2007;Lee et al, 2008;Konduri et al, 2009).…”

Section: Discussionmentioning

confidence: 93%

Chemopreventive effect of tolfenamic acid on KB human cervical cancer cells and tumor xenograft by downregulating specificity protein 1

Shim¹,

Shin²,

Jung

et al. 2011

European Journal of Cancer Prevention

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Earlier studies have shown that tolfenamic acid (Tol) exhibits anticancer activity in several cancer models by inhibiting tumor growth and angiogenesis. However, the chemopreventive effect of Tol on a cervical cancer model and the underlying mechanism of action are unknown. In this study, Tol was found to inhibit cell proliferation by inducing apoptosis without affecting cyclo-oxygenase 2 expression, but ampiroxicam did not. Tol decreases the specificity protein 1 (Sp1) mRNA and its promoter activity in KB cervical cancer cells, and the downregulation of Sp1 protein by affecting several proteins that contain GC-rich sites on their promoters. Studies using small interference RNA and an Sp1-specific inhibitor (mithramycin A) confirmed that the decrease in Sp1 by Tol affects survivin and p27. Tol also inhibited tumor growth and Sp1 protein in athymic nude mice xenografts. These results show that Tol could be a potent anticervical cancer drug that acts by regulating Sp1 protein and its downstream pathways.

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Section: Discussionmentioning

confidence: 93%

Chemopreventive effect of tolfenamic acid on KB human cervical cancer cells and tumor xenograft by downregulating specificity protein 1

Shim¹,

Shin²,

Jung

et al. 2011

European Journal of Cancer Prevention

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“…Tolfenamic acid is remarkably non-irritative towards the gastric mucosa (Axelsson et al 1977), is well tolerated by the patients and has shown good results in clinical studies, including long-term treatment of rheumatoid arthritis (Kajander et al 1976;Nyfos 1979;Rejholec et al 197914 & B;Sorensen & Christiansen 1977;Zachariae & Sylvest 1972). Clinical efficacy in dysmenorrhoea (Kauppila & Ylikorkala 1977;Kauppila et al 1979;Kim et al 1983) and migraine (Hakkarainen et al 1979;Mikkelsen & Falk 1982;Mikkelsen et al 1986; has also been documented.…”

Section: Introductionmentioning

confidence: 99%

Biopharmaceutical Aspects of Tolfenamic Acid

Pedersen¹

1994

Pharmacology & Toxicology

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The pharmacokinetics of tolfenamic acid is well described by a two-compartment model with relatively short half-lives (T/2 beta 1-2 hours) and tolfenamic acid is highly protein-bound with small volumes of distribution. It is cleared relatively fast (150-200 ml/min), mainly by hepatic metabolism and the metabolites are renally cleared as glucuronic acid conjugates. The peroral absorption is good and the peroral bioavailability is about 75%, as first pass metabolism accounts for about 20%. Tolfenamic acid shows linear pharmacokinetics and during multiple dosage regimen, i.e. thrice daily, no accumulation beyond the second dose is observed. The bioavailability in dependence of age and disease has been studied and only in the case of severe liver or kidney impairment, a change in dosage regimen seems warranted. The development of different formulations will be outlined, mainly on rectal delivery, on sustained release and rapid release oral formulations, on topical ointment, and on parenteral delivery. The problems with tolfenamic acid in pharmaceutical formulation caused mainly by poor solubility will be discussed. Formulations ready for the market now or very soon are Clotam capsules (tablets). Clotam retard tablets, Clotam suppositories, and Clotam oral suspension, whereas rapid tablets, topical ointments, and parenteral formulations need further development to be ready for marketing in the years to come.

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“…(7) It possesses analgesic and antipyretic properties, as demonstrated in several animal models, and has shown good results in the treatment of osteoarthritis and rheumatoid arthritis. (8)(9)(10) Recent studies have suggested that Tol also affects apoptosis in colorectal cancer cells as well as metastasis and tumorigenesis in pancreatic cancer models. (11)(12)(13) However, there are no reports on the role of Tol or its molecular basis on the apoptosis of prostate cancer cells.Specificity protein 1 (Sp1) is an essential transcription factor for many genes essential for the regulation of multiple aspects of tumor cell survival, growth and angiogenesis, (14)(15)(16) and the abnormal expression of Sp1 may contribute to cancer development and progression.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Apoptotic effect of tolfenamic acid in androgen receptor‐independent prostate cancer cell and xenograft tumor through specificity protein 1

et al. 2011

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Tolfenamic acid (Tol) is a non-steroidal anti-inflammatory drug that was reported to exhibit anticancer activity in pancreatic and colorectal cancer models. This study examined the role of Tol in the death regulation of PC-3 and DU145 human androgen-independent prostate cancer cells. The results showed that Tol inhibited cell growth and induced apoptosis, as evidenced by nuclear fragmentation and cleaved caspase 3 and poly(ADP-ribose) polymerase. Tol suppressed the specificity protein 1 (Sp1) protein in both PC-3 and DU145 cells. Tol also attenuated Sp1 mRNA and its promoter activity in DU145 cells, but did not alter them in PC-3 cells, indicating that Tol degrades Sp1 protein in these cells. Tol also downregulated protein levels, mRNA levels and promoter activities of survivin and myeloid cell leukemia-1, which are downstream targets of Sp1. The expressions of survivin and Mcl-1 and cancer cell growth were lower in the PC-3 cells treated with Sp1 interfering RNA and mithramycin A. Moreover, an oral injection of Tol decreased tumor growth and downregulated the Sp1 protein in athymic nude mice bearing DU145 cell xenografts without hepatotoxicity. Overall, Tol downregulates the Sp1 protein to inhibit growth and induce apoptosis in androgen-refractory prostate cancers, both in vitro and in vivo, that show resistance against many chemotherapeutic agents. (Cancer Sci 2011; 102: 742-748)

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Osteoarthritis of the Knee Treated with Tolfenamic Acid

Cited by 12 publications

References 5 publications

Chemopreventive effect of tolfenamic acid on KB human cervical cancer cells and tumor xenograft by downregulating specificity protein 1

Chemopreventive effect of tolfenamic acid on KB human cervical cancer cells and tumor xenograft by downregulating specificity protein 1

Biopharmaceutical Aspects of Tolfenamic Acid

Apoptotic effect of tolfenamic acid in androgen receptor‐independent prostate cancer cell and xenograft tumor through specificity protein 1

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