Effects of leptin on the viability of MCF-7 and T47D cells at different glucose concentrations

Yıl 2020, Cilt: 37 Sayı: 4, 119 - 125, 11.09.2020

Pınar Demirel Soner Dogan Ümit Özorhan Bilge Güvenç Tuna Todd Schuster Margot Cleary

Öz

Obesity is associated with increased risk of breast cancer. Leptin is a well-known factor involved in obesity and its serum levels are increased in breast cancer. Hyperglycemia is another significant risk factor for breast cancer. Consistently, high glucose induces proliferation and invasion of breast cancer cells and in vivo calorie restriction reduces tumorigenesis in rodent models. The aim of this study was to investigate the effect of leptin on the viability and mode of cell death in breast cancer cells incubated in different glucose concentrations to represent caloric restriction. For this purpose, MCF-7 and T47D breast cancer cells incubated in different glucose concentrations for a total of 72 hours were treated with or without leptin either for one hour or 24 hours and the ratio of apoptotic, necrotic and alive cells were analyzed by flow cytometry. Our data revealed that glucose incubation significantly decreased apoptosis and necrosis, while increasing viability in both cell lines in a dose dependent manner. One-hour leptin treatment significantly decreased viability, and increased apoptosis but did not significantly affect necrosis in T47D cells incubated in 2.5 mM glucose. In MCF-7 cells, one-hour leptin incubation significantly increased necrosis but its effects on apoptosis and viability were not significant. In conclusion, glucose induces cell death by apoptosis and necrosis in T47D and MCF-7 cells, respectively in a dose dependent manner. One-hour leptin treatment reverses the effect of low glucose incubation on apoptosis of T47D and necrosis of MCF-7 cells. Moreover, the effect of one-hour leptin treatment on apoptosis or necrosis is significantly higher than that of 24-hour leptin treatment.

Anahtar Kelimeler

Leptin, Glucose, MCF-7, T47D, Cancer, Breast Cancer, Cell Viability

Destekleyen Kurum

NIH (National Institute of Health) and The Breast Cancer Research Foundation and The Hormel Foundation, Minnesota.

Proje Numarası

CA101858 and CA157012 (MPC) and The Breast Cancer Research Foundation and The Hormel Foundation, Minnesota.

Teşekkür

This work was supported by grants NIH-CA101858, CA157012 (MPC) and The Breast Cancer Research Foundation and The Hormel Foundation, Minnesota. The authors thank summer intern undergraduate student, Swetha S. Ramanan, for helping us maintaining the cell culture.

Kaynakça

• 1. Amitani, M., Asakawa, A., Amitani, H., Inui, A. 2013. The role of leptin in the control of insulin-glucose axis. Front. Neurosci.7, 51.
• 2. Artac, M., Altundag, K. 2012. Leptin and breast cancer: an overview. Med. Oncol. 29(3),1510-4.
• 3. Boyle, P., Boniol, M., Koechlin, A., Robertson, C., Valentini, F., Coppens, K., Fairley, L.L., Boniol, M., Zheng, T., Zhang, Y., Pasterk, M., Smans, M., Curado, M.P., Mullie, P., Gandini, S., Bota, M., Bolli, G.B., Rosenstock, J., Autier, P. 2012. Diabetes and breast cancer risk: a meta-analysis. Br. J. Cancer. 107(9),1608-17.
• 4. Chan, D.S., Vieira, A.R., Aune, D., Bandera, E.V., Greenwood, D.C., McTiernan, A., Navarro Rosenblatt, D., Thune, I., Vieira, R., Norat, T. 2014. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann. Oncol. 25(10),1901-14.
• 5. D'Souza, A.M., Neumann, U.H., Glavas, M.M., Kieffer, T.J. 2017. The glucoregulatory actions of leptin. Mol. Metab. 6(9), 1052-65.
• 6. Dogan, S., Hu, X., Zhang, Y., Maihle, N.J., Grande, J.P., Cleary, M.P. 2007. Effects of high fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-alpha mice. Breast Cancer Res. 9(6), R91.
• 7. Dogan, S., Johannsen, A.C., Grande, J.P., Cleary, M.P. 2011. Effects of intermittent and chronic calorie restriction on mammalian target of rapamycin (mTOR) and IGF-I signaling pathways in mammary fat pad tissues and mammary tumors. Nutr. cancer. 63(3),389-401.
• 8. Dogan, S., Rogozina, O.P., Lokshin, A.E., Grande, J.P., Cleary, M.P. 2010. Effects of chronic vs. intermittent calorie restriction on mammary tumor incidence and serum adiponectin and leptin levels in MMTV-TGF-alpha mice at different ages. Oncol. Lett. 1(1),167-76.
• 9. Duan, W., Shen, X., Lei, J., Xu, Q., Yu, Y., Li, R., Wu, E., Ma, Q. 2014. Hyperglycemia, a neglected factor during cancer progression. Biomed. Res. Int. 2014, 461917.
• 10. Hedbacker, K., Birsoy, K., Wysocki, R.W., Asilmaz, E., Ahima, R.S., Farooqi, I.S., Friedman, J.M. 2010. Antidiabetic effects of IGFBP2, a leptin-regulated gene. Cell Metab. 11(1), 11-22.
• 11. Hou, Y., Zhou, M., Xie, J., Chao, P., Feng, Q., Wu, J. 2017. High glucose levels promote the proliferation of breast cancer cells through GTPases. Breast Cancer (Dove Med Press). 9, 429-36.
• 12. Hu, X., Juneja, S.C., Maihle, N.J., Cleary, M.P. 2002. Leptin--a growth factor in normal and malignant breast cells and for normal mammary gland development. J. Natl. Cancer Inst. 94(22), 1704-11.
• 13. Ishikawa, M., Kitayama, J., Nagawa, H. 2004. Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clin, Cancer Res. 10(13),4325-31.
• 14. Johnson, J.A., Carstensen, B., Witte, D., Bowker, S.L., Lipscombe, L., Renehan, A.G. 2012. Diabetes and cancer (1): evaluating the temporal relationship between type 2 diabetes and cancer incidence. Diabetologia. 55(6),1607-18.
• 15. Keum, N., Greenwood, D.C., Lee, D.H., Kim, R., Aune, D., Ju, W., Hu, F.B., Giovannucci, E.L. 2015. Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of prospective observational studies. J. Natl. Cancer Inst.107(2).
• 16. Kretowski, R., Borzym-Kluczyk, M., Stypulkowska, A., Branska-Januszewska, J., Ostrowska, H., Cechowska-Pasko, M. 2016. Low glucose dependent decrease of apoptosis and induction of autophagy in breast cancer MCF-7 cells. Mol. Cell Biochem. 417(1-2),35-47.
• 17. Ligibel, J. Obesity and breast cancer. 2011. Oncology (Williston Park). 25(11), 994-1000.
• 18. Mooney, L.M., Al-Sakkaf, K.A., Brown, B.L., Dobson, P.R. 2002. Apoptotic mechanisms in T47D and MCF-7 human breast cancer cells. Br. J. Cancer. 87(8), 909-17.
• 19. Muti, P., Quattrin, T., Grant, B.J., Krogh, V., Micheli, A., Schünemann, H.J., Ram, M., Freudenheim, J.L., Sieri, S., Trevisan, M., Berrino, F. 2002. Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol. Biomarkers Prev. 11(11),1361-8.
• 20. Neve, R.M., Chin, K., Fridlyand, J., Yeh, J., Baehner, F.L., Fevr, T., Clark, L., Bayani, N., Coppe, J.P., Tong, F., Speed, T., Spellman, P.T., DeVries, S., Lapuk, A., Wang, N.J., Kuo, W.L., Stilwell, J.L., Pinkel, D., Albertson, D.G., Waldman, F.M., McCormick, F., Dickson, R.B., Johnson, M.D., Lippman, M., Ethier, S., Gazdar, A., Gray, J.W. 2006. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 10(6), 515-27.
• 21. Niu, J., Jiang, L., Guo, W., Shao, L., Liu, Y., Wang, L. 2013. The Association between Leptin Level and Breast Cancer: A Meta-Analysis. PLoS One. 8(6), e67349.
• 22. O'Flanagan, C.H., Smith, L.A., McDonell, S.B., Hursting, S.D. 2017. When less may be more: calorie restriction and response to cancer therapy. BMC Med. 15(1),106.
• 23. Okumura, M., Yamamoto, M., Sakuma, H., Kojima, T., Maruyama, T., Jamali, M., Cooper, D.R., Yasuda, K. 2002. Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: reciprocal involvement of PKC-alpha and PPAR expression. Biochim. Biophys. Acta. 1592(2),107-16.
• 24. Pelleymounter, M.A., Cullen, M.J., Baker, M.B., Hecht, R., Winters, D., Boone, T., Collins, F. 1995. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 269(5223), 540-3.
• 25. Ryu, T.Y., Park, J., Scherer, P.E. 2014. Hyperglycemia as a risk factor for cancer progression. Diabetes Metab. J. 38(5),330-6.
• 26. Tuna, B.G., Atalay, P.B., Altunbek, M., Kalkan, B.M., Dogan, S. 2017. Effects of Chronic and Intermittent Calorie Restriction on Adropin Levels in Breast Cancer. Nutr. cancer. 69(7), 1003-10.
• 27. Vigneri, P., Frasca, F., Sciacca, L., Pandini, G., Vigneri, R. 2009. Diabetes and cancer. Endocr. Relat. Cancer. 16(4),1103-23.
• 28. Wei, M.L., Duan, P., Wang, Z.M., Ding, M., Tu, P. 2017. High glucose and high insulin conditions promote MCF7 cell proliferation and invasion by upregulating IRS1 and activating the Ras/Raf/ERK pathway. Mol. Med. Rep. 16(5),6690-6.
• 29. Wu, M.H., Chou, Y.C., Chou, W.Y., Hsu, G.C., Chu, C.H., Yu, C.P., Yu, J.C., Sun, C.A. 2009. Circulating levels of leptin, adiposity and breast cancer risk. Br. J. Cancer. 100(4),578-82.
• 30. Yamamoto, M., Patel, N.A., Taggart, J., Sridhar, R., Cooper, D.R. 1999. A shift from normal to high glucose levels stimulates cell proliferation in drug sensitive MCF-7 human breast cancer cells but not in multidrug resistant MCF-7/ADR cells which overproduce PKC-betaII. Int. J. Cancer. 83(1),98-106.