Effects of Indomethacin on Expression of PTEN Tumour Suppressor in Human Cancers

Overview

Journal Niger Med J

Specialty General Medicine

Date 2013 Jun 27

PMID 23798795

Citations 3

Authors

Imran Haruna Abdulkareem

Maria Blair

Affiliations

Soon will be listed here.

Abstract

Background: Previous studies reported that Non-steroidal Anti-inflammatory Drugs (NSAIDs), chemicals, and food supplements can be used to up-regulate the PTEN mRNA and protein expression, suggesting that these substances may be used in prevention and/or treatment of various human cancers like spinal, brain, colon, breast, prostate, bladder and endometrial cancers.

Aim: This was to study expression and sub-cellular localisation of PTEN protein, and review the effect(s) of indomethacin on PTEN's expression in cultured Human Endometrial Cancer (HEC 1B) cell line, which is known to express significant amounts of the wild-type PTEN.

Materials And Methods: This involves culture and incubation of artificial HEC 1B cells. All procedures were undertaken in the cell culture hood under the recommended sterile conditions. The cells were then incubated with different concentrations of indomethacin solution, for variable durations and finally fixed (with paraformaldehyde) and stained with fluorescein-labelled diluted secondary antibody (FITC). Immunocytochemistry (IHC) and fluorescent microscopy were then employed for the detection and localisation of the specific antigen (PTEN), using antibodies.

Results: The HEC 1B cells, which were cultured and incubated with different concentrations of indomethacin solution, expressed the PTEN protein, most of which was localised to the nucleus with minimal cytoplasmic expression. Increased PTEN expression was observed following treatment of the cells with various concentrations of the solution for variable durations, although there was cell death at higher concentrations and longer duration. This procedure was repeated several times, in order to have consistency and to validate the results.

Conclusion: This study agrees with previous studies in similar human cell lines and supports the idea that NSAIDs and other drugs may be used in the future for prevention of human cancers. However, more studies need to be carried out to substantiate these observations.

Citing Articles

Biological Activity of -[Re(CO)(phen)(aspirin)], -[Re(CO)(phen)(indomethacin)] and Their Original Counterparts against Ishikawa and HEC-1A Endometrial Cancer Cells.

Kuzmycz O, Kowalczyk A, Staczek P Int J Mol Sci. 2022; 23(19).

PMID: 36232870 PMC: 9569891. DOI: 10.3390/ijms231911568.

Prospects of NSAIDs administration as double-edged agents against endometrial cancer and pathological species of the uterine microbiome.

Kuzmycz O, Staczek P Cancer Biol Ther. 2020; 21(6):486-494.

PMID: 32174282 PMC: 7515452. DOI: 10.1080/15384047.2020.1736483.

Clinicopathological significance of PTEN and PI3K/AKT signal transduction pathway in non-small cell lung cancer.

Yun F, Jia Y, Li X, Yuan L, Sun Q, Yu H Int J Clin Exp Pathol. 2013; 6(10):2112-20.

PMID: 24133589 PMC: 3796233.

References

Li D, Sun H . TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res. 1997; 57(11):2124-9. View

Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang S . PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997; 275(5308):1943-7. DOI: 10.1126/science.275.5308.1943. View

Herlevsen M, Oxford G, Ptak C, Shabanowitz J, Hunt D, Conaway M . A novel model to identify interaction partners of the PTEN tumor suppressor gene in human bladder cancer. Biochem Biophys Res Commun. 2006; 352(2):549-55. PMC: 1933505. DOI: 10.1016/j.bbrc.2006.11.067. View

Stiles B, Groszer M, Wang S, Jiao J, Wu H . PTENless means more. Dev Biol. 2004; 273(2):175-84. DOI: 10.1016/j.ydbio.2004.06.008. View

Lazcoz P, Munoz J, Nistal M, Pestana A, Encio I, Castresana J . Loss of heterozygosity and microsatellite instability on chromosome arm 10q in neuroblastoma. Cancer Genet Cytogenet. 2007; 174(1):1-8. DOI: 10.1016/j.cancergencyto.2006.08.014. View

Steck P, Pershouse M, Jasser S, Yung W, Lin H, Ligon A . Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997; 15(4):356-62. DOI: 10.1038/ng0497-356. View

Li H, Bubley G, Balk S, Gaziano J, Pollak M, Stampfer M . Hypoxia-inducible factor-1alpha (HIF-1alpha) gene polymorphisms, circulating insulin-like growth factor binding protein (IGFBP)-3 levels and prostate cancer. Prostate. 2007; 67(12):1354-61. DOI: 10.1002/pros.20589. View

Leslie N, Downes C . PTEN: The down side of PI 3-kinase signalling. Cell Signal. 2002; 14(4):285-95. DOI: 10.1016/s0898-6568(01)00234-0. View

Sharrard R, Maitland N . Regulation of protein kinase B activity by PTEN and SHIP2 in human prostate-derived cell lines. Cell Signal. 2006; 19(1):129-38. DOI: 10.1016/j.cellsig.2006.05.029. View

10.

Tsao H, Goel V, Wu H, Yang G, Haluska F . Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma. J Invest Dermatol. 2004; 122(2):337-41. PMC: 2586668. DOI: 10.1046/j.0022-202X.2004.22243.x. View

11.

Jin X, Gossett D, Wang S, Yang D, Cao Y, Chen J . Inhibition of AKT survival pathway by a small molecule inhibitor in human endometrial cancer cells. Br J Cancer. 2004; 91(10):1808-12. PMC: 2410058. DOI: 10.1038/sj.bjc.6602214. View

12.

Gericke A, Munson M, Ross A . Regulation of the PTEN phosphatase. Gene. 2006; 374:1-9. DOI: 10.1016/j.gene.2006.02.024. View

13.

Priulla M, Calastretti A, Bruno P, Azzariti A, Amalia A, Angelo Paradiso . Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase. Prostate. 2007; 67(7):782-9. DOI: 10.1002/pros.20566. View

14.

Liaw D, Marsh D, Li J, Dahia P, Wang S, Zheng Z . Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet. 1997; 16(1):64-7. DOI: 10.1038/ng0597-64. View

15.

Norimatsu Y, Moriya T, Kobayashi T, Sakurai T, Shimizu K, Tsukayama C . Immunohistochemical expression of PTEN and beta-catenin for endometrial intraepithelial neoplasia in Japanese women. Ann Diagn Pathol. 2007; 11(2):103-8. DOI: 10.1016/j.anndiagpath.2006.06.009. View

16.

Stambolic V, Macpherson D, Sas D, Lin Y, Snow B, Jang Y . Regulation of PTEN transcription by p53. Mol Cell. 2001; 8(2):317-25. DOI: 10.1016/s1097-2765(01)00323-9. View

17.

Yaginuma Y, Yamashita T, Ishiya T, Morizaki A, Katoh Y, Takahashi T . Abnormal structure and expression of PTEN/MMAC1 gene in human uterine cancers. Mol Carcinog. 2000; 27(2):110-6. DOI: 10.1002/(sici)1098-2744(200002)27:2<110::aid-mc6>3.0.co;2-e. View

18.

Flores-Delgado G, Liu C, Sposto R, Berndt N . A limited screen for protein interactions reveals new roles for protein phosphatase 1 in cell cycle control and apoptosis. J Proteome Res. 2007; 6(3):1165-75. DOI: 10.1021/pr060504h. View

19.

Kim S, Domon-Dell C, Wang Q, Chung D, Di Cristofano A, Pandolfi P . PTEN and TNF-alpha regulation of the intestinal-specific Cdx-2 homeobox gene through a PI3K, PKB/Akt, and NF-kappaB-dependent pathway. Gastroenterology. 2002; 123(4):1163-78. DOI: 10.1053/gast.2002.36043. View

20.

Sulis M, Parsons R . PTEN: from pathology to biology. Trends Cell Biol. 2003; 13(9):478-83. DOI: 10.1016/s0962-8924(03)00175-2. View