Effects of the Inhibition of Cytosolic Phospholipase A(2)α in Non-small Cell Lung Cancer Cells

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2012 Jan 26

PMID 22274867

Citations 8

Authors

Shenbagamoorthy Sundarraj

Soundarapandian Kannan

Ramar Thangam

Palani Gunasekaran

Affiliations

Soon will be listed here.

Abstract

Purpose: The aim of this study was to investigate the expression of cPLA(2)α in non-small lung cancer cell lines and tissues, and we sought to determine the in vitro effects of the pyrrolidine-2 inhibitor on cPLA(2)α sensitivity in three different non-small lung cancer cell lines.

Methods: The expression of cPLA(2)α was determined in lung cancer cells by Western blot. Cytotoxicity, cell growth and inhibition of cPLA(2)α activity were determined in relation to the concentration of pyrrolidine-2. Finally, this study investigated immunohistochemical expressions of cPLA(2)α in 23 species of human non-small lung cancer and 5 species of human normal lung to assess their clinicopathological relevance.

Results: cPLA(2)α is expressed in A549 and H460, however, no expression in H661 cells. Pyrrolidine-2 demonstrated a dose-dependent inhibitory effect on cell growth and its significantly inhibited BrdU incorporation of human non-small lung cancer cells. Inhibition with pyrrolidine-2 results in reduction in cPLA(2)α activity in A549 and H460 lung cancer cells by 50% when present at IC(50) concentration in arachidonoyl thio-PC assay. Immunohistochemistry of human lung tissue revealed that cPLA(2)α is increased in lung cancer tissues.

Conclusions: Pyrrolidine-2 is a more potent and specific cPLA(2)α inhibitor than MAFP and AACOCF3 and represents an excellent pharmacological tool to investigate the biosynthesis and the biological roles of cancer. The present study suggests that pyrrolidine-2 could be a potential therapeutic agent for cancer therapy.

Citing Articles

Survival prediction in acute myeloid leukemia using gene expression profiling.

Lai B, Lai Y, Zhang Y, Zhou M, Ouyang G BMC Med Inform Decis Mak. 2022; 22(1):57.

PMID: 35241089 PMC: 8892720. DOI: 10.1186/s12911-022-01791-z.

A Novel 85-Gene Expression Signature Predicts Unfavorable Prognosis in Acute Myeloid Leukemia.

Lai Y, Sheng L, Wang J, Zhou M, Ouyang G Technol Cancer Res Treat. 2021; 20:15330338211004933.

PMID: 33784904 PMC: 8020099. DOI: 10.1177/15330338211004933.

Novel prognostic genes and subclasses of acute myeloid leukemia revealed by survival analysis of gene expression data.

Lai Y, Ouyang G, Sheng L, Zhang Y, Lai B, Zhou M BMC Med Genomics. 2021; 14(1):39.

PMID: 33536020 PMC: 7860023. DOI: 10.1186/s12920-021-00888-0.

Identifying a novel 5-gene signature predicting clinical outcomes in acute myeloid leukemia.

Sha K, Lu Y, Zhang P, Pei R, Shi X, Fan Z Clin Transl Oncol. 2020; 23(3):648-656.

PMID: 32776271 DOI: 10.1007/s12094-020-02460-1.

Modeling Membrane Curvature Generation due to Membrane⁻Protein Interactions.

Alimohamadi H, Rangamani P Biomolecules. 2018; 8(4).

PMID: 30360496 PMC: 6316661. DOI: 10.3390/biom8040120.

References

Laye J, Gill J . Phospholipase A2 expression in tumours: a target for therapeutic intervention?. Drug Discov Today. 2003; 8(15):710-6. DOI: 10.1016/s1359-6446(03)02754-5. View

Ono T, Yamada K, Chikazawa Y, Ueno M, Nakamoto S, Okuno T . Characterization of a novel inhibitor of cytosolic phospholipase A2alpha, pyrrophenone. Biochem J. 2002; 363(Pt 3):727-35. PMC: 1222525. DOI: 10.1042/0264-6021:3630727. View

Sundarraj S, Kannan S . Immunohistochemical expression of cytosolic phospholipase A2α in non-small cell lung carcinoma. Asian Pac J Cancer Prev. 2011; 11(5):1367-72. View

Sawaoka H, Tsuji S, Tsujii M, Gunawan E, Sasaki Y, Kawano S . Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Lab Invest. 2000; 79(12):1469-77. View

Seno K, Okuno T, Nishi K, Murakami Y, Watanabe F, Matsuura T . Pyrrolidine inhibitors of human cytosolic phospholipase A(2). J Med Chem. 2000; 43(6):1041-4. DOI: 10.1021/jm9905155. View

Hughes-Fulford M, Tjandrawinata R, Li C, Sayyah S . Arachidonic acid, an omega-6 fatty acid, induces cytoplasmic phospholipase A2 in prostate carcinoma cells. Carcinogenesis. 2005; 26(9):1520-6. DOI: 10.1093/carcin/bgi112. View

Jackson B, Goldstein R, Roy R, Cozzani M, Taylor L, Polgar P . Effects of transforming growth factor beta and interleukin-1 beta on expression of cyclooxygenase 1 and 2 and phospholipase A2 mRNA in lung fibroblasts and endothelial cells in culture. Biochem Biophys Res Commun. 1993; 197(3):1465-74. DOI: 10.1006/bbrc.1993.2642. View

Korystov YuN , Shaposhnikova V, Levitman M, Kudryavtsev A, Kublik L, Narimanov A . The effect of inhibitors of arachidonic acid metabolism on proliferation and death of tumor cells. FEBS Lett. 1998; 431(2):224-6. DOI: 10.1016/s0014-5793(98)00757-1. View

Ghomashchi F, Stewart A, Hefner Y, Ramanadham S, Turk J, Leslie C . A pyrrolidine-based specific inhibitor of cytosolic phospholipase A(2)alpha blocks arachidonic acid release in a variety of mammalian cells. Biochim Biophys Acta. 2001; 1513(2):160-6. DOI: 10.1016/s0005-2736(01)00349-2. View

10.

Pidgeon G, Kandouz M, Meram A, Honn K . Mechanisms controlling cell cycle arrest and induction of apoptosis after 12-lipoxygenase inhibition in prostate cancer cells. Cancer Res. 2002; 62(9):2721-7. View

11.

Ikawa H, Kamitani H, Calvo B, Foley J, Eling T . Expression of 15-lipoxygenase-1 in human colorectal cancer. Cancer Res. 1999; 59(2):360-6. View

12.

Wendum D, Comperat E, Boelle P, Parc R, Masliah J, Trugnan G . Cytoplasmic phospholipase A2 alpha overexpression in stromal cells is correlated with angiogenesis in human colorectal cancer. Mod Pathol. 2004; 18(2):212-20. DOI: 10.1038/modpathol.3800284. View

13.

Zhu Y, Azahri N, Yu D, Woll P . Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells. BMC Cancer. 2008; 8:218. PMC: 2516523. DOI: 10.1186/1471-2407-8-218. View

14.

Hirabayashi T, Shimizu T . Localization and regulation of cytosolic phospholipase A(2). Biochim Biophys Acta. 2000; 1488(1-2):124-38. DOI: 10.1016/s1388-1981(00)00115-3. View

15.

Wu T, Han C, Lunz 3rd J, Michalopoulos G, Shelhamer J, Demetris A . Involvement of 85-kd cytosolic phospholipase A(2) and cyclooxygenase-2 in the proliferation of human cholangiocarcinoma cells. Hepatology. 2002; 36(2):363-73. DOI: 10.1053/jhep.2002.34743. View

16.

Blaine S, Wick M, Dessev C, Nemenoff R . Induction of cPLA2 in lung epithelial cells and non-small cell lung cancer is mediated by Sp1 and c-Jun. J Biol Chem. 2001; 276(46):42737-43. DOI: 10.1074/jbc.M107773200. View

17.

Osterstrom A, Dimberg J, Fransen K, Soderkvist P . Expression of cytosolic and group X secretory phospholipase A(2) genes in human colorectal adenocarcinomas. Cancer Lett. 2002; 182(2):175-82. DOI: 10.1016/s0304-3835(02)00081-2. View

18.

Ghosh M, Tucker D, Burchett S, Leslie C . Properties of the Group IV phospholipase A2 family. Prog Lipid Res. 2006; 45(6):487-510. DOI: 10.1016/j.plipres.2006.05.003. View

19.

Seno K, Okuno T, Nishi K, Murakami Y, Yamada K, Nakamoto S . Pyrrolidine inhibitors of human cytosolic phospholipase A2. Part 2: synthesis of potent and crystallized 4-triphenylmethylthio derivative 'pyrrophenone'. Bioorg Med Chem Lett. 2001; 11(4):587-90. DOI: 10.1016/s0960-894x(01)00003-8. View

20.

Lehr M, Griessbach K . Involvement of different protein kinases and phospholipases A2 in phorbol ester (TPA)-induced arachidonic acid liberation in bovine platelets. Mediators Inflamm. 2000; 9(1):31-4. PMC: 1781745. DOI: 10.1080/09629350050024357. View