Tolfenamic acid inhibits ovarian cancer cell growth and decreases the expression of c-Met and survivin through suppressing specificity protein transcription factors

Basha, Riyaz; Ingersoll, Susan B.; Sankpal, Umesh T.; Ahmad, Sarfraz; Baker, Cheryl H.; Edwards, John; Holloway, Robert W.; Kaja, Sumanth; Abdelrahim, Maen

doi:10.1016/j.ygyno.2011.03.014

Cited by 55 publications

(42 citation statements)

References 40 publications

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“…2). Cancer cell growth inhibition was accompanied with a decrease in the expression of both Sp1 and survivin in all three pancreatic cancer cell lines, which is also consistent with published pre-clinical work on pancreatic [26] and other cancers [30,32,35,36,37]. Notably, non-malignant hTERT-HPNE cells do not express survivin but do express Sp1, but TA treatment did not affect the expression of Sp1.…”

Section: Discussionsupporting

confidence: 89%

“…As expected, TA caused minimal effect on differentiated NB cells when compared to un-differentiated SH-SY5Y cells. Recent studies from our group demonstrated that TA induces apoptotic pathways and disrupts cell cycle progression in cancer cells [30,32,35,36,37]. It is plausible that apoptotic and cell cycle processes/pathways are potentially inactive in differentiated cells, thereby reducing the effect of TA in RA treated (differentiated) SH-SY5Y cells.…”

Section: Discussionmentioning

confidence: 99%

“…Pre-clinical studies from our laboratory and others demonstrated the anti-cancer and chemopreventive response of tolfenamic acid (TA, 2-(4-chloro-3-methylanilino)benzoic acid) in a variety of human cancers. TA has been studied in pre-clinical models for adult (pancreatic [26,27], lung [28], esophageal [14,29], ovarian [30], prostate [31,32], and colon [33,34]) cancers and pediatric (leukemia [35], neuroblastoma [36], and medulloblastoma [37]) malignancies. Experimental results from our laboratory also showed a chemopreventive effect by this drug in an animal model of esophageal cancer [29,38].…”

Section: Introductionmentioning

confidence: 99%

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Cellular and Organismal Toxicity of the Anti-Cancer Small Molecule, Tolfenamic Acid: a Pre-Clinical Evaluation

Sankpal¹,

Lee²,

Connelly³

et al. 2013

Cell Physiol Biochem

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Background/Aims: The small molecule, Tolfenamic acid (TA) has shown anti-cancer activity in pre-clinical models and is currently in Phase I clinical trials at MD Anderson Cancer Center Orlando. Since specificity and toxicity are major concerns for investigational agents, we tested the effect of TA on specific targets, and assessed the cellular and organismal toxicity representing pre-clinical studies in cancer. Methods: Panc1, L3.6pl, and MiaPaCa-2 (pancreatic cancer), hTERT-HPNE(normal), and differentiated/un-differentiated SH-SY5Y (neuroblastoma) cells were treated with increasing concentrations of TA. Cell viability and effect on specific molecular targets, Sp1 and survivin were determined. Athymic nude mice were treated with vehicle or TA (50mg/kg, 3times/week for 6 weeks) and alterations in the growth pattern, hematocrit, and histopathology of gut, liver, and stomach were monitored. Results: TA treatment decreased cell proliferation and inhibited the expression of Sp1 and survivin in cancer cells while only subtle response was observed in normal (hTERT-HPNE) and differentiated SH-SY5Y cells. Mice studies revealed no effect on body weight and hematocrit. Furthermore, TA regimen did not cause signs of internal-bleeding or damage to vital tissues in mice. Conclusion: These results demonstrate that TA selectively inhibits malignant cell growth acting on specific targets and its chronic treatment did not cause apparent toxicity in nude mice.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cellular and Organismal Toxicity of the Anti-Cancer Small Molecule, Tolfenamic Acid: a Pre-Clinical Evaluation

Sankpal¹,

Lee²,

Connelly³

et al. 2013

Cell Physiol Biochem

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“…TA treatment inhibited in vivo tumorigenesis through downregulating vascular endothelial growth factor (VEGF) and its receptor (VEGFR1) [27]. TA also decreased c-Met and survivin through suppressing specificity proteins (Sp) [19,24]. By using human colorectal cancer cells, we observed that TA-stimulated apoptosis is associated with up-regulation of pro-apoptotic proteins, early growth response-1 (EGR-1) and activating transcription factor 3 (ATF3) [14,15].…”

mentioning

confidence: 93%

“…Tolfenamic acid (TA) is a (N-(2-methyl-3-chlorophenyl)-anthranilic acid and possesses anti-cancer activity in several cancers such as pancreatic cancer [13], colorectal cancer [14][15][16], lung cancer [17], breast cancer [18], ovarian cancer [19], prostate cancer [20,21], brain cancer [22,23], esophageal cancer [24], sarcoma [25] and head and neck cancer [26]. Anti-cancer effect by TA is influenced by expressions of various cancer-related genes and cell signaling pathways.…”

Section: Introductionmentioning

confidence: 99%