Effects of vitamin D on proliferation, invasion and energy metabolism of MCF-7 breast cancer cell line

Year 2022, Volume: 52 Issue: 3, 311 - 317, 30.12.2022

Emine Nedime Korucu Ali Unlu

https://doi.org/10.26650/IstanbulJPharm.2022.1133531

Abstract

Background and Aims: 1,25(OH)2D3 (vitamin D) is a pleiotropic hormone with anti-proliferative, pro-apoptotic, and pro- differentiation effects on various cell types, which suggest anti-cancer activity in addition to its classical regulatory action on calcium and phosphate metabolism.
Methods: We aimed to put forward the effects of vitamin D in various concentrations and time intervals on cell proliferation and invasion of human estrogen receptor-positive breast cancer (MCF-7) cells by real-time cell electronic sensing system (xCELLigence). A determined dose of the IC50 was applied on samples taken from cell lysates and analyzed the levels of the energy. We also aimed to clarify how vitamin D effects the activity of the protease uPA and their relations with each other.
Results: Vitamin D showed a cytotoxic effect on MCF-7 cells in a time and dose dependent manner, with dose of IC50 found to be 140 nM. ATP, ADP, and AMP levels, as well as uPA activities were respectively increased in vitamin D treatment group compared to the control group for the first 24 hours while decreasing at 48, 72, and 96 hours. We determined that 70 and 140 nM vitamin D were decreased in invasion of MCF-7 cells compared to control cells.
Conclusion: We observed that proliferation and invasion of breast cancer cells were inhibited by vitamin D treatment on a dose and time dependent manner, and also vitamin D supplementation decreased uPA activity and energy levels. Further studies on the mechanisms of vitamin D and the formulation of none-hypercalcemic analogues in featured are needed.

Keywords

Activity of uPA, Energy levels, Invasion, Proliferation, Vitamin D

Supporting Institution

Selcuk University Scientific Research Project

Project Number

11202002

References

• Abbas, S., Chang‐Claude, J., & Linseisen, J. (2009). Plasma 25‐hy- droxyvitamin D and premenopausal breast cancer risk in a Ger- man case‐control study. International journal of cancer, 124(1), 250-255.
• Anderson, P. H. (2017). Vitamin D Activity and Metabolism in Bone. Current Osteoporosis Reports, 15(5), 443-449. doi:10.1007/ s11914-017-0394-8
• Brosseau, C., Pirianov, G., & Colston, K. (2010). Involvement of stress activated protein kinases (JNK and p38) in 1, 25 dihydroxyvitamin D3-induced breast cell death. Steroids, 75(13-14), 1082-1088.
• Chiang, K. C., Chen, S. C., Yeh, C. N., Pang, J. H., Shen, S. C., Hsu, J. T., Chen, T. C. (2014). MART-10, a less calcemic vitamin D analog, is more potent than 1alpha,25-dihydroxyvitamin D3 in inhibit- ing the metastatic potential of MCF-7 breast cancer cells in vitro. Journal of Steroid Biochemistry and Molecular Biology, 139, 54-60. doi:10.1016/j.jsbmb.2013.10.005
• Cimen, B., Turkozkan, N., Unlu, A., & Erbil, M. K. (2005). Effects of melatonin on 3-nitrotyrosine formation and energy charge ratio in guinea pig kidney in LPS-induced stress. Cell Biochemistry and Function, 23(4), 273-277. doi:10.1002/cbf.1151
• Diesing, D., Cordes, T., Fischer, D., Diedrich, K., & Friedrich, M. (2006). Vitamin D--metabolism in the human breast cancer cell line MCF-7. Anticancer Research, 26(4A), 2755-2759.
• Dinicola, S., Pasqualato, A., Cucina, A., Coluccia, P., Ferranti, F., Cani- pari, R., . . . Bizzarri, M. (2014). Grape seed extract suppresses MDA- MB231 breast cancer cell migration and invasion. European Jour- nal of Nutrition, 53(2), 421-431. doi:10.1007/s00394-013-0542-6
• Duffy, M. J., & Duggan, C. (2004). The urokinase plasminogen ac- tivator system: a rich source of tumour markers for the individu- alised management of patients with cancer. Clinical Biochemistry, 37(7), 541-548. doi:10.1016/j.clinbiochem.2004.05.013
• Fehm, T., Zwirner, M., Wallwiener, D., Seeger, H., & Neubauer, H. (2012). Antitumor activity of zoledronic acid in primary breast cancer cells determined by the ATP tumor chemosensitivity as- say. BMC Cancer, 12, 308. doi:10.1186/1471-2407-12-308
• Flanagan, L., Packman, K., Juba, B., O’Neill, S., Tenniswood, M., & Welsh, J. (2003). Efficacy of Vitamin D compounds to modulate estrogen receptor negative breast cancer growth and invasion. Journal of Steroid Biochemistry and Molecular Biology, 84(2-3), 181- 192.
• Friedrich, M., Diesing, D., Cordes, T., Fischer, D., Becker, S., Chen, T. C., . . . Reichrath, J. (2006). Analysis of 25-hydroxyvitamin D3- 1alpha-hydroxylase in normal and malignant breast tissue. Anti- cancer Research, 26(4A), 2615-2620.
• Garland, C., Garland, F., Gorham, E., & Raffa, J. (1991). Sunlight, vi- tamin D, and mortality from breast and colorectal cancer in Italy. Biologie Effects of Light, 39.
• Garland, C. F., Garland, F. C., Gorham, E. D., Lipkin, M., Newmark, H., Mohr, S. B., & Holick, M. F. (2006). The role of vitamin D in cancer prevention. American journal of public health, 96(2), 252-261.
• Kamińska, M., Ciszewski, T., Łopacka-Szatan, K., Miotła, P., & Starosławska, E. (2015). Breast cancer risk factors. Przeglad meno- pauzalny= Menopause review, 14(3), 196.
• Kaur, G., Behrsing, H., Parchment, R. E., Millin, M. D., & Teicher, B. A. (2013). Analyses of the combination of 6-MP and dasatinib in cell culture. International Journal of Oncology, 43(1), 13-22. doi:10.3892/ijo.2013.1930
• Kim, H. A., Kim, M. S., Kim, S. H., & Kim, Y. K. (2014). Pepper seed ex- tract suppresses invasion and migration of human breast cancer cells. Nutrition and Cancer, 66(1), 159-165. doi:10.1080/01635581. 2014.853814
• Lim, H. S., Roychoudhuri, R., Peto, J., Schwartz, G., Baade, P., & Moller, H. (2006). Cancer survival is dependent on season of di- agnosis and sunlight exposure. International Journal of Cancer, 119(7), 1530-1536. doi:10.1002/ijc.22052
• Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193(1), 265-275.
• Marchionatti, A. M., Picotto, G., Narvaez, C. J., Welsh, J., & Tolosa de Talamoni, N. G. (2009). Antiproliferative action of menadione and 1,25(OH)2D3 on breast cancer cells. Journal of Steroid Bio- chemistry and Molecular Biology, 113(3-5), 227-232. doi:10.1016/j. jsbmb.2009.01.004
• Mathiasen, I. S., Lademann, U., & Jäättelä, M. (1999). Apoptosis in- duced by vitamin D compounds in breast cancer cells is inhibited by Bcl-2 but does not involve known caspases or p53. Cancer re- search, 59(19), 4848-4856.
• Meijer-van Gelder, M. E., Look, M. P., Peters, H. A., Schmitt, M., Brünner, N., Harbeck, N., . . . Foekens, J. A. (2004). Urokinase-type plasminogen activator system in breast cancer: association with tamoxifen therapy in recurrent disease. Cancer Research, 64(13), 4563-4568.
• Ning, Y. L., Qi, C. J., Lu, X. Z., Zhu, Y. L., Qian, K. Q., & Zhao, J. Z. (2011). The predictive value of epidermal growth factor receptor expres- sion for sensitivity to vinorelbine in breast cancer. Basic & Clinical Pharmacology & Toxicology, 109(6), 499-505. doi:10.1111/j.1742- 7843.2011.00759.x
• Ooi, L. L., Zheng, Y., Zhou, H., Trivedi, T., Conigrave, A. D., Seibel, M. J., & Dunstan, C. R. (2010). Vitamin D deficiency promotes growth of MCF-7 human breast cancer in a rodent model of os- teosclerotic bone metastasis. Bone, 47(4), 795-803. doi:10.1016/j. bone.2010.07.012
• Pavlova, N. N., & Thompson, C. B. (2016). The emerging hallmarks of cancer metabolism. Cell metabolism, 23(1), 27-47.
• Porojnicu, A. C., Lagunova, Z., Robsahm, T. E., Berg, J. P., Dahlback, A., & Moan, J. (2007). Changes in risk of death from breast cancer with season and latitude: sun exposure and breast cancer survival in Norway. Breast Cancer Research and Treatment, 102(3), 323-328. doi:10.1007/s10549-006-9331-8
• Proietti, S., Cucina, A., D’Anselmi, F., Dinicola, S., Pasqualato, A., Lisi, E., & Bizzarri, M. (2011). Melatonin and vitamin D3 synergistically down-regulate Akt and MDM2 leading to TGFbeta-1-dependent growth inhibition of breast cancer cells. Journal of Pineal Research, 50(2), 150-158. doi:10.1111/j.1600-079X.2010.00824.x
• Robsahm, T. E., Tretli, S., Dahlback, A., & Moan, J. (2004). Vitamin D3 from sunlight may improve the prognosis of breast-, colon- and prostate cancer (Norway). Cancer Causes Control, 15(2), 149-158. doi:10.1023/b:caco.0000019494.34403.09
• Rossi, M., McLaughlin, J. K., Lagiou, P., Bosetti, C., Talamini, R., Lip- worth, L., . . . La Vecchia, C. (2009). Vitamin D intake and breast cancer risk: a case-control study in Italy. Annals of Oncology, 20(2), 374-378. doi:10.1093/annonc/mdn550
• Schmitt, M., Harbeck, N., Thomssen, C., Wilhelm, O., Magdolen, V., Reuning, U., . . . Graeff, H. (1997). Clinical impact of the plasmino- gen activation system in tumor invasion and metastasis: prog- nostic relevance and target for therapy. Thrombosis and haemo- stasis, 78(01), 285-296.
• Sliva, D. (2004). Signaling pathways responsible for cancer cell in- vasion as targets for cancer therapy. Current Cancer Drug Targets, 4(4), 327-336.
• So, J. Y., Smolarek, A. K., Salerno, D. M., Maehr, H., Uskokovic, M., Liu, F., & Suh, N. (2013). Targeting CD44-STAT3 signaling by Gemini vi- tamin D analog leads to inhibition of invasion in basal-like breast cancer. PLoS One, 8(1), e54020. doi:10.1371/journal.pone.0054020
• Sucha, L., Hroch, M., Rezacova, M., Rudolf, E., Havelek, R., Sispera, L., . . . Tomsik, P. (2013). The cytotoxic effect of alpha-tomatine in MCF-7 human adenocarcinoma breast cancer cells depends on its interaction with cholesterol in incubation media and does not involve apoptosis induction. Oncology Reports, 30(6), 2593-2602. doi:10.3892/or.2013.2778
• Sundaram, S., Beckman, M. J., Bajwa, A., Wei, J., Smith, K. M., Posner, G. H., & Gewirtz, D. A. (2006). QW-1624F2-2, a synthetic analogue of 1,25-dihydroxyvitamin D3, enhances the response to other deltanoids and suppresses the invasiveness of human metastatic breast tumor cells. Molecular Cancer Therapeutics, 5(11), 2806- 2814. doi:10.1158/1535-7163.mct-06-0092
• Uitterlinden, A. G., Fang, Y., Van Meurs, J. B., Pols, H. A., & Van Leeu- wen, J. P. (2004). Genetics and biology of vitamin D receptor poly- morphisms. Gene, 338(2), 143-156. doi:10.1016/j.gene.2004.05.014
• Veldhuis, S., Wolbers, F., Brouckaert, O., Vermes, I., & Franke, H. R. (2011). Cancer prevalence in osteoporotic women with low se- rum vitamin D levels. Menopause, 18(3), 319-322. doi:10.1097/ gme.0b013e3181f81ad5
• Welsh, J. (2021). Vitamin D and Breast Cancer: Mechanistic Up- date. JBMR plus, 5(12), e10582.
• Wietzke, J. A., & Welsh, J. (2003). Phytoestrogen regulation of a Vitamin D3 receptor promoter and 1,25-dihydroxyvitamin D3 ac- tions in human breast cancer cells. Journal of Steroid Biochemistry and Molecular Biology, 84(2-3), 149-157.