Crosstalk between possible cytostatic and antiinflammatory potential of ketoprofen in the treatment of culture of colon and cervix cancer cell lines

Damnjanović, Ivana; Najman, Stevo; Stojanović, Sanja; Stojanović, Dušica; Veljković, Andrej; Kocic, Hristina; Langerholc, Tomaž; Damnjanović, Zoran; Pešić, Milica

doi:10.4149/bll_2015_044

Cited by 9 publications

(8 citation statements)

References 21 publications

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“…45−47 However, a significant cytostatic effect was observed upon exposure of human cervical carcinoma (HeLa) and human colon cancer cells (Caco-2) to ketoprofen, which may be attributed to the NF-κB inhibition that was detected. 16…”

Section: Results and Discussionmentioning

confidence: 99%

Carboranyl Analogues of Ketoprofen with Cytostatic Activity against Human Melanoma and Colon Cancer Cell Lines

et al. 2019

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Ketoprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) that also exhibits cytotoxic activity against various cancers. This makes ketoprofen an attractive structural lead for the development of new NSAIDs and cytotoxic agents. Recently, the incorporation of carboranes as phenyl mimetics in structures of established drugs has emerged as an attractive strategy in drug design. Herein, we report the synthesis and evaluation of four novel carborane-containing derivatives of ketoprofen, two of which are prodrug esters with an nitric oxide-releasing moiety. One of these prodrug esters exhibited high cytostatic activity against melanoma and colon cancer cell lines. The most pronounced activity was found in cell lines that are sensitive to oxidative stress, which was apparently induced by the ketoprofen analogue.

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Section: Results and Discussionmentioning

confidence: 99%

Carboranyl Analogues of Ketoprofen with Cytostatic Activity against Human Melanoma and Colon Cancer Cell Lines

et al. 2019

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“…One of the antiproliferative mechanisms of this drug is the transcription factor of NF-κB because NF-κB was evident at low doses of ketoprofen. Given that NF-κB is controlled by the modified expression of COX-2, the inhibition of this enzyme by ketoprofen is an important step in the treatment and prevention of colon and cervix cancer (25). Previous studies have accurately examined the effects of some NSAIDs in treating colon cancer, and their results indicated the importance of NSAIDs in the treatment and prevention of cancer (26).…”

Section: Discussionmentioning

confidence: 99%

Anti-cancer Effects of Ketoprofen on the Expression of HE4 Gene and Viability of the A2780 Human Ovarian Cancer Cell Line

Yahyaie¹,

Morovati-Sharifabad²,

Salehi³

et al. 2021

Jentashapir J Cell Mol Biol

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Background: Ovarian cancer is the second leading cause of death in Iran compared with other gynecological diseases. Considering the role of cyclooxygenase (COX) enzymes and prostaglandin E2 production in tumor lesions, nonsteroidal anti-inflammatory drugs (NSAIDs) show antitumor properties by inhibiting COX. Furthermore, some compounds can serve as non-selective inhibitors of COX (such as ketoprofen) and prevent cancer development. Human epididymis protein 4 (HE4) is one of the most sensitive tumor markers known in the study of the disease of ovarian epithelial cancer. The expression of HE4 increases in different types of ovarian cancer. Objectives: The aim of this study was to determine the anti-cancer effects of ketoprofen on the viability of ovarian cancer cells and expression of HE4 gene. Methods: To calculate half-maximal inhibitory concentration (IC50), A2780S cells were treated with different concentrations of ketoprofen for 24 hours, then the cells were incubated with appropriate concentrations of IC50 for 24, 48, and 72 hours. Real-time polymerase chain reaction (PCR) was used to measure changes caused by the effect of drugs on HE4 gene expression and analyzed by the 2-ΔΔCT method. Results: The IC50 level of ketoprofen for 24 hours was 583.7 μM. According to real-time PCR results, treatment of cells with ketoprofen reduced HE4 expression. Conclusions: HE4 gene expression decreased in cells treated with ketoprofen compared with the cells in the control group, which proves the anti-cancer activity of ketoprofen and a reduction in the viability of ovarian cancer cells.

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“…A large number of epidemiological and experimental studies have revealed that prolonged treatment with non-steroidal anti-inflammatory drugs (NSAIDs), which are COX inhibitors, can reduce the risk of cancer (13). NSAIDs inhibit cell proliferation and induce apoptosis of a number of cancer cells in vitro and in vivo, which is considered to be an important mechanism for the anti-tumor and chemopreventive activity of NSAIDs (14). However, the molecular pathways of this process are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of Potential Synergi Stic Effect of Ketoprofen and Melox Icam With Convention Al Cytostatics in Human Cervix Cancer Cell Line

Damnjanović¹,

Kocić²,

Najman³

et al. 2018

AMM

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Cyclooxygenases clearly appear to be implicated in carcinogenesis. It has been reported that COX-2 is active throughout the entire process of cancer development and progression. Various molecular mechanisms may be responsible for this. Epidemiological and experimental studies have revealed that nonselective non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors can reduce the risk of cancer. Inhibition of COX provides a plausible explanation of the data on NSAIDs and cancer. However, the molecular pathways of this effect are still unclear, more complex and likely involve multiple COX-2dependent and independent mechanisms, where pro-and anti-apoptotic Bcl-2 family members may take part. We examined the effects of ketoprofen (KT), as nonselective COX-1/2, and meloxicam (MK), as selective COX-2 inhibitor, alone and combined with 5-fluorouarcil (FU) and cisplatin (CP), on the proliferation by MTT test and Bcl-2/Bax expression in HeLa cells (human cervical carcinoma cells). MC alone or combined with conventional anticancer drugs, FU and CP, showed better cytotoxic and antiproliferative effect than KT. The levels of Bcl-2 were decreased while the levels of Bax were increased dose-dependently by KT and MC. A significant increase in the expression of Bax protein in HeLa cells was more pronounced for MC. The synergy observed in the effects of ketoprofen and meloxicam with cisplatin and 5fluorouracil on the cervical cancer cell line was generated by an enhancement of apoptosis. Therefore, ketoprofen and meloxicam may represent therapeutic candidates to improve access of cervical cancer chemoprevention and chemotherapy.

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Crosstalk between possible cytostatic and antiinflammatory potential of ketoprofen in the treatment of culture of colon and cervix cancer cell lines

Cited by 9 publications

References 21 publications

Carboranyl Analogues of Ketoprofen with Cytostatic Activity against Human Melanoma and Colon Cancer Cell Lines

Carboranyl Analogues of Ketoprofen with Cytostatic Activity against Human Melanoma and Colon Cancer Cell Lines

Anti-cancer Effects of Ketoprofen on the Expression of HE4 Gene and Viability of the A2780 Human Ovarian Cancer Cell Line

Molecular Mechanisms of Potential Synergi Stic Effect of Ketoprofen and Melox Icam With Convention Al Cytostatics in Human Cervix Cancer Cell Line

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