Piroxicam induced alteration on membrane depolarization and caspase levels in PC3 prostate cancer cells

Cemile Şahiner Kışla; Filiz Bakar Ateş

Piroxicam induced alteration on membrane depolarization and caspase levels in PC3 prostate cancer cells

Abstract

The relationship between cancer and inflammation has been known for years, and the interaction between prostate cancer and inflammation and inflammatory agents is still under investigation. Studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs), which are effective in the treatment of inflammation, can also be effective in some types of cancer. In this study, the efficacy of piroxicam on human prostate cancer cells was evaluated. Piroxicam showed a significant cytotoxic effect in PC-3 cells at a concentration of 50 µM and above at the 48th hour, and induced cell cycle arrest in the S phase. On the other hand, piroxicam was found to increase annexin V binding in PC3 cells, and the early apoptotic cell population was found to be significantly higher at 25 µM and higher concentrations (p<0.05). The apoptosis-inducing effect of piroxicam was also confirmed by high total caspase levels (p<0.0001). In addition, increased membrane depolarization was observed in PC3 cells treated with piroxicam. In conclusion, this study showed the cytotoxic and apoptotic effect of piroxicam in PC-3 cells, and the obtained findings shed light on further studies on the use of piroxicam as a promising compound in prostate cancer.

Keywords

References

[1] Bray F, Ferlay J, Soerjomataram I, Sıegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2018;68(6):394. [CrossRef]
[2] Beatty J. Viral causes of feline lymphoma: Retroviruses and beyond. Vet J. 2014;201:174-180. [CrossRef]
[3] De Falco M, Lucarıello A, Iaquınto S, Esposito V, Guerra G, De Luca A. Molecular mechanisms of Helicobacter pylori pathogenesis. J Cell Physiol. 2015;230(8):1702-1707. [CrossRef]
[4] Rothman I, Stanford JL, Kuniyuki A, Berger RE. Self-report of prostatitis and its risk factors in a random sample of middle-aged men. Urology. 2004;64:876-879. [CrossRef]
[5] Nelson WG, De Marzo AM, Deweese TL, Isaacs WB. The role of inflammation in the pathogenesis of prostate cancer. J Urol. 2004;172(5):6-12. [CrossRef]
[6] Rosenblatt KA, Wicklund KG, Stanford JL. Sexual factors and the risk of prostate cancer. Am J Epidemiol. 2001;153:1152-1158. [CrossRef]
[7] Loftus EV Jr. Epidemiology and risk factors for colorectal dysplasia and cancer in ulcerative colitis. Gastroenterol Clin North Am. 2006;35:517-531. [CrossRef]
[8] Sethi G, Shanmugam MK, Ramachandran L, Kumar AP, Tergaonkar V. Multifaceted link between cancer and inflammation. Biosci Rep. 2012;32:1-15. [CrossRef]

[9] Kundu JK, Surh YJ. Emerging avenues linking inflammation and cancer. Free Radic Biol Med. 2012;52:2013–2037. [CrossRef]
[10] Sica A, Allavena P, Mantovani A. Cancer related inflammation: the macrophage connection. Cancer Lett. 2008;267:204-215. [CrossRef]
[11] Ang HL, Tergaonkar V. Notch and NFκB signaling pathways: do they collaborate in normal vertebrate brain development and function? BioEssays. 2007;29:1039-1047. [CrossRef]
[12] Chai EZP, Siveen KS, Shanmugam MK, Arfuso F, Sethi G. Analysis of the intricate relationship between chronic inflammation and cancer. Biochem J. 2015;468:1-15. [CrossRef]
[13] Rakoff-Nahoum S. Why cancer and inflammation? Yale J Biol Med. 2006;79:123-130.
[14] Norrish AE, Jackson RT, McRae CU. Non-steroidal anti-inflammatory drugs and prostate cancer progression. Int J Cancer. 1998;77:511-515. [CrossRef]
[15] Nelson JE, Harris RE. Inverse association of prostate cancer and non-steroidal anti-inflammatory drugs (NSAIDs): results of a case–control study. Oncol Rep. 2000;7:169-170. [CrossRef]
[16] Roberts RO, Jacobson DJ, Girman CJ, Rhodes T, Lieber MM, Jacobsen SJ. A population-based study of daily nonsteroidal anti-inflammatory drug use and prostate cancer. Mayo Clin Proc. 2002;77:219-225. [CrossRef]
[17] Kirschenbaum A, Liu X, Yao S, Levine AC. The role of cyclooxygenase-2 in prostate cancer. Urology. 2001;58:127-131. [CrossRef]
[18] Tjandrawinata RR, Hughes-Fulford M. Up-regulation of cyclooxygenase-2 by product-prostaglandin E2. Adv Exp Med Biol. 1997;407:163-170. [CrossRef]
[19] Liu XH, Kirschenbaum A, Lu M, Yao S, et al. Prostaglandin E(2) stimulates prostatic intraepithelial neoplasia cell growth through activation of the interleukin-6/GP130/STAT-3 signaling pathway. Biochem Biophys Res Commun. 2002;290:249-255. [CrossRef]
[20] Campione E, Paternò EJ, Candi E, et al. The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors. Drug Des Devel Ther. 2015;9:5843-5850. [CrossRef]
[21] Jetter N, Chandan N, Wang S, Tsoukas M. Field cancerization therapies for management of actinic keratosis: A narrative review. Am J Clin Dermatol. 2018;19:543–557. [CrossRef]
[22] Balkwill F, Mantovani A. Inflammation and cancer: Back to Virchow? Lancet. 2001;357:539–545. [CrossRef]
[23] Rayburn E, Ezell SJ, Zhang R. Anti-inflammatory agents for cancer therapy. Mol Cell Pharmacol. 2009;1(1):29–43. [CrossRef]
[24] Jiao J, Ishikawa TO, Dumlao DS, et al. Targeted deletion and lipidomic analysis identify epithelial cell COX-2 as a major driver of chemically induced skin cancer. Mol Cancer Res. 2014;12:1677–1688. [CrossRef]
[25] Wang W, Bergh A, Damber JE. Morphological transition of proliferative inflammatory atrophy to high-grade intraepithelial neoplasia and cancer in human prostate. Prostate. 2009;69(13):1378–1386. [CrossRef]
[26] Wu K, Fukuda K, Xing F, et al. Roles of the cyclooxygenase 2 matrix metalloproteinase 1 pathway in brain metastasis of breast cancer. J Biol Chem. 2015;290:9842–9854. [CrossRef]
[27] Qu L, Liu B. Cyclooxygenase-2 promotes metastasis in osteosarcoma. Cancer Cell Int. 2015;15:69. [CrossRef]
[28] Misron NA, Looi LM, Nik Mustapha NRN. Cyclooxygenase-2 expression in invasive breast carcinomas of no special type and correlation with pathological profiles suggest a role in tumorigenesis rather than cancer progression. Asian Pac J Cancer Prev. 2015;16:1553–1558. [CrossRef]
[29] Park WS, Lee HK, Lee JY, et al. p53 mutations in solar keratoses. Hum Pathol. 1996;27(11):1180–1184. [CrossRef]
[30] Sharpe CR, Collet JP, McNutt M, et al. Nested case-control study of the effects of nonsteroidal anti-inflammatory drugs on breast cancer risk and stage. Br J Cancer. 2000;83:112–120. [CrossRef]
[31] Khuder SA, Mutgi AB. Breast cancer and NSAID use: A meta-analysis. Br J Cancer. 2001;84:1188–1192. [CrossRef]
[32] Alshafie GA, Abou-Issa HM, Seibert K, Harris RE. Chemotherapeutic evaluation of celecoxib, a cyclooxygenase-2 inhibitor, in a rat mammary tumour model. Oncol Rep. 2000;7:1377–1381. [CrossRef]
[33] Yao M, Zhou W, Sangha S, et al. Effects of nonselective cyclooxygenase inhibition with low-dose ibuprofen on tumor growth, angiogenesis, metastasis, and survival in a mouse model of colorectal cancer. Clin Cancer Res. 2005;11(4):1618–1628. [CrossRef]
[34] Kanda A, Ebihara S, Takahashi H, Sasaki H. Loxoprofen sodium suppresses mouse tumor growth by inhibiting vascular endothelial growth factor. Acta Oncol. 2009;42(1):62–70. [CrossRef]
[35] Hossain MA, Kim DH, Jang JY, et al. Aspirin enhances doxorubicin-induced apoptosis and reduces tumour growth in human hepatocellular carcinoma cells in vitro and in vivo. Int J Oncol. 2012;40(5):1636–1642. [CrossRef]
[36] Diluvio L, Bavetta M, Costanza G, et al. Monitoring treatment response in patients affected by actinic keratosis: Dermoscopic assessment and metalloproteinases evaluation after piroxicam 0.8% and sunfilter cream. Dermatol Ther. 2019;32(1):e12772. [CrossRef]
[37] Gorsky VA, Agapov MA, Khoreva MV, et al. The effect of lornoxicam on TLR2 and TLR4 messenger RNA expression and tumor necrosis factor-α, interleukin-6, and interleukin-8 secretion in patients with systemic complications of acute pancreatitis. Pancreas. 2015;44(5):824–830. [CrossRef]
[38] Jiao H, Ren F. Pretreatment with lornoxicam, a cyclooxygenase inhibitor, relieves postoperative immunosuppression after total abdominal hysterectomy. Tohoku J Exp Med. 2009;219(4):289–294. [CrossRef]
[39] Mirshafiey A, Vaezzadeh F, Khorramizadeh MR, Saadat F. Effect of piroxicam on matrix metalloproteinase 2 and apoptosis. Int J Tissue React. 2004;26(1-2):1–7.
[40] Pollard M, Luckert PH. Indomethacin treatment of rats with dimethylhydrazine-induced intestinal tumors. Cancer Treat Rep. 1980;64:1323–1327.
[41] Rai N, Sarkar M, Raha S. Piroxicam, a traditional non-steroidal anti-inflammatory drug (NSAID), causes apoptosis by ROS mediated Akt activation. Pharmacol Rep. 2015;67:1215–1223. [CrossRef]
[42] Bakar-Ates F, Ozkan E. The combined treatment of brassinin and imatinib synergistically downregulated the expression of MMP-9 in SW480 colon cancer cells. Phytother Res. 2019;33(2):397–402. [CrossRef]
[43] Celik A, Bakar-Ates F. The confounding effect of interleukin-6 on apoptosis of MCF-7 cells through downregulation of MMP-2/-9 mRNA expression. Turkish J Biochem. 2021;46:549–555. [CrossRef]
[44] Ergul M, Bakar-Ates F. Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021;73:105138. [CrossRef]

Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Cemile Şahiner Kışla This is me
Türkiye

Filiz Bakar Ateş ^*
Türkiye

Publication Date

June 28, 2025

Submission Date

April 12, 2022

Acceptance Date

July 18, 2022

Published in Issue

Year 2022 Volume: 26 Number: 6

IZ

https://izlik.org/JA44BJ57TS

Cite

RIS / Bibtex

APA

Şahiner Kışla, C., & Bakar Ateş, F. (2025). Piroxicam induced alteration on membrane depolarization and caspase levels in PC3 prostate cancer cells. Journal of Research in Pharmacy, 26(6), 1646-1655. https://izlik.org/JA44BJ57TS

AMA

1.Şahiner Kışla C, Bakar Ateş F. Piroxicam induced alteration on membrane depolarization and caspase levels in PC3 prostate cancer cells. J. Res. Pharm. 2025;26(6):1646-1655. https://izlik.org/JA44BJ57TS

Chicago

Şahiner Kışla, Cemile, and Filiz Bakar Ateş. 2025. “Piroxicam Induced Alteration on Membrane Depolarization and Caspase Levels in PC3 Prostate Cancer Cells”. Journal of Research in Pharmacy 26 (6): 1646-55. https://izlik.org/JA44BJ57TS.

EndNote

Şahiner Kışla C, Bakar Ateş F (June 1, 2025) Piroxicam induced alteration on membrane depolarization and caspase levels in PC3 prostate cancer cells. Journal of Research in Pharmacy 26 6 1646–1655.

IEEE

[1]C. Şahiner Kışla and F. Bakar Ateş, “Piroxicam induced alteration on membrane depolarization and caspase levels in PC3 prostate cancer cells”, J. Res. Pharm., vol. 26, no. 6, pp. 1646–1655, June 2025, [Online]. Available: https://izlik.org/JA44BJ57TS

ISNAD

Şahiner Kışla, Cemile - Bakar Ateş, Filiz. “Piroxicam Induced Alteration on Membrane Depolarization and Caspase Levels in PC3 Prostate Cancer Cells”. Journal of Research in Pharmacy 26/6 (June 1, 2025): 1646-1655. https://izlik.org/JA44BJ57TS.

JAMA

1.Şahiner Kışla C, Bakar Ateş F. Piroxicam induced alteration on membrane depolarization and caspase levels in PC3 prostate cancer cells. J. Res. Pharm. 2025;26:1646–1655.

MLA

Şahiner Kışla, Cemile, and Filiz Bakar Ateş. “Piroxicam Induced Alteration on Membrane Depolarization and Caspase Levels in PC3 Prostate Cancer Cells”. Journal of Research in Pharmacy, vol. 26, no. 6, June 2025, pp. 1646-55, https://izlik.org/JA44BJ57TS.

Vancouver

1.Cemile Şahiner Kışla, Filiz Bakar Ateş. Piroxicam induced alteration on membrane depolarization and caspase levels in PC3 prostate cancer cells. J. Res. Pharm. [Internet]. 2025 Jun. 1;26(6):1646-55. Available from: https://izlik.org/JA44BJ57TS