Celecoxib and Bcl-2: Emerging Possibilities for Anticancer Drug Design

Overview

Journal Future Med Chem

Specialties Chemistry
Pharmacy

Date 2012 Mar 8

PMID 22393942

Citations 6

Authors

Leyte L Winfield

Florastina Payton-Stewart

Affiliations

Soon will be listed here.

Abstract

Celecoxib is a multifaceted drug with promising anticancer properties. A number of studies have been conducted that implicate the compound in modulating the expression of Bcl-2 family members and mitochondria-mediated apoptosis. The growing data surrounding the role of celecoxib in the regulation of the mitochondrial death pathway provides a platform for ongoing debate. Studies that describe celecoxib's properties as a BH3 mimic or as a direct inhibitor of Bcl-2 are not available. The motivations for this review are: to provide the basis for the development of novel compounds that modulate Bcl-2 expression using celecoxib as a structural starting point and to encourage additional biological studies (such as binding and enzymatic assays) that would provide information regarding celecoxib's role as a Bcl-2 antagonist. The current review summarizes work that identifies the role of celecoxib in blocking the activity of Bcl-2.

Citing Articles

Celecoxib and rofecoxib have different effects on small intestinal ischemia/reperfusion injury in rats.

Laszlo S, Hutka B, Toth A, Hegyes T, Demeter Z, Haghighi A Front Pharmacol. 2024; 15:1468579.

PMID: 39584137 PMC: 11582421. DOI: 10.3389/fphar.2024.1468579.

Concomitant effects of paclitaxel and celecoxib on genes involved in apoptosis of triple-negative metastatic breast cancer cells.

Hedayat M, Khezri M, Jafari R, Malekinejad H, Zolbanin N Med Oncol. 2023; 40(9):263.

PMID: 37548777 DOI: 10.1007/s12032-023-02119-1.

Discovery and Therapeutic Exploitation of Mechanisms of Resistance to MET Inhibitors in Glioblastoma.

Cruickshanks N, Zhang Y, Hine S, Gibert M, Yuan F, Oxford M Clin Cancer Res. 2018; 25(2):663-673.

PMID: 30201763 PMC: 6335175. DOI: 10.1158/1078-0432.CCR-18-0926.

Advances in the proteomic discovery of novel therapeutic targets in cancer.

Guo S, Zou J, Wang G Drug Des Devel Ther. 2013; 7:1259-71.

PMID: 24187485 PMC: 3810204. DOI: 10.2147/DDDT.S52216.

Triggering of suicidal erythrocyte death by celecoxib.

Lupescu A, Bissinger R, Jilani K, Lang F Toxins (Basel). 2013; 5(9):1543-54.

PMID: 24025609 PMC: 3798872. DOI: 10.3390/toxins5091543.

References

Reed S, Li H, Li C, Lin J . Celecoxib inhibits STAT3 phosphorylation and suppresses cell migration and colony forming ability in rhabdomyosarcoma cells. Biochem Biophys Res Commun. 2011; 407(3):450-5. DOI: 10.1016/j.bbrc.2011.03.014. View

Nagase Y, Iwasawa M, Akiyama T, Kadono Y, Nakamura M, Oshima Y . Anti-apoptotic molecule Bcl-2 regulates the differentiation, activation, and survival of both osteoblasts and osteoclasts. J Biol Chem. 2009; 284(52):36659-36669. PMC: 2794780. DOI: 10.1074/jbc.M109.016915. View

Sun W, Chen G, Ou X, Yang Y, Luo C, Zhang Y . Inhibition of COX-2 and activation of peroxisome proliferator-activated receptor gamma synergistically inhibits proliferation and induces apoptosis of human pancreatic carcinoma cells. Cancer Lett. 2008; 275(2):247-55. DOI: 10.1016/j.canlet.2008.10.023. View

Williams C, Sheng H, Brockman J, Armandla R, Shao J, Washington M . A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts. Neoplasia. 2001; 3(5):428-36. PMC: 1506203. DOI: 10.1038/sj.neo.7900177. View

De Chiara G, Marcocci M, Torcia M, Lucibello M, Rosini P, Bonini P . Bcl-2 Phosphorylation by p38 MAPK: identification of target sites and biologic consequences. J Biol Chem. 2006; 281(30):21353-21361. DOI: 10.1074/jbc.M511052200. View

Kaloustian S, Wann B, Bah T, Falcao S, Dufort A, Ryvlin P . Celecoxib after the onset of reperfusion reduces apoptosis in the amygdala. Apoptosis. 2007; 12(11):1945-51. DOI: 10.1007/s10495-007-0122-4. View

Chen J, Chen Y, Su Y, Tseng S . Celecoxib increased expression of 14-3-3sigma and induced apoptosis of glioma cells. Anticancer Res. 2007; 27(4B):2547-54. View

Chattopadhyay S, Bhattacharyya S, Saha B, Chakraborty J, Mohanty S, Sakib Hossain D . Tumor-shed PGE(2) impairs IL2Rgammac-signaling to inhibit CD4 T cell survival: regulation by theaflavins. PLoS One. 2009; 4(10):e7382. PMC: 2753647. DOI: 10.1371/journal.pone.0007382. View

Adams J, Cory S . The Bcl-2 protein family: arbiters of cell survival. Science. 1998; 281(5381):1322-6. DOI: 10.1126/science.281.5381.1322. View

10.

Yuan Z, Wang F, Zhao Z, Zhao X, Qiu J, Nie C . BIM-mediated AKT phosphorylation is a key modulator of arsenic trioxide-induced apoptosis in cisplatin-sensitive and -resistant ovarian cancer cells. PLoS One. 2011; 6(5):e20586. PMC: 3105099. DOI: 10.1371/journal.pone.0020586. View

11.

Verdine G, Walensky L . The challenge of drugging undruggable targets in cancer: lessons learned from targeting BCL-2 family members. Clin Cancer Res. 2007; 13(24):7264-70. DOI: 10.1158/1078-0432.CCR-07-2184. View

12.

Anether G, Tinhofer I, Senfter M, Greil R . Tetrocarcin-A--induced ER stress mediates apoptosis in B-CLL cells via a Bcl-2--independent pathway. Blood. 2003; 101(11):4561-8. DOI: 10.1182/blood-2002-08-2501. View

13.

Yu P, Liu Q, Liu K, Yagasaki K, Wu E, Zhang G . Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-kappaB signaling. Cytotechnology. 2009; 59(3):219-29. PMC: 2774574. DOI: 10.1007/s10616-009-9225-9. View

14.

Gallicchio M, Rosa A, Dianzani C, Brucato L, Benetti E, Collino M . Celecoxib decreases expression of the adhesion molecules ICAM-1 and VCAM-1 in a colon cancer cell line (HT29). Br J Pharmacol. 2007; 153(5):870-8. PMC: 2267284. DOI: 10.1038/sj.bjp.0707634. View

15.

Arlorio M, Bottini C, Travaglia F, Locatelli M, Bordiga M, Coisson J . Protective activity of Theobroma cacao L. phenolic extract on AML12 and MLP29 liver cells by preventing apoptosis and inducing autophagy. J Agric Food Chem. 2009; 57(22):10612-8. DOI: 10.1021/jf902419t. View

16.

Elder D, Halton D, Hague A, Paraskeva C . Induction of apoptotic cell death in human colorectal carcinoma cell lines by a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug: independence from COX-2 protein expression. Clin Cancer Res. 1998; 3(10):1679-83. View

17.

Tacconelli S, Capone M, Patrignani P . Clinical pharmacology of novel selective COX-2 inhibitors. Curr Pharm Des. 2004; 10(6):589-601. DOI: 10.2174/1381612043453108. View

18.

Kumar P, Ning Y, Polverini P . Endothelial cells expressing Bcl-2 promotes tumor metastasis by enhancing tumor angiogenesis, blood vessel leakiness and tumor invasion. Lab Invest. 2008; 88(7):740-9. DOI: 10.1038/labinvest.2008.46. View

19.

Azmi A, Wang Z, Philip P, Mohammad R, Sarkar F . Emerging Bcl-2 inhibitors for the treatment of cancer. Expert Opin Emerg Drugs. 2010; 16(1):59-70. PMC: 3084453. DOI: 10.1517/14728214.2010.515210. View

20.

Chen Y, Tsai Y, Tseng S . Combined valproic acid and celecoxib treatment induced synergistic cytotoxicity and apoptosis in neuroblastoma cells. Anticancer Res. 2011; 31(6):2231-9. View