Document Type : Research Paper

Authors

1 MSC. Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

2 Assistant Professor, Department of Animal Sciences and Marine Biology, Faculty of Biological Sciences and Technology, Shahid Beheshti University, Tehran, Iran

10.22051/jab.2024.45435.1596

Abstract

Introduction: Breast cancer is the most common type of cancer among women in the world. Research is ongoing to find new and less risky ways to treat breast cancer. Recent studies on the effect of Alpha-ketoglutarate (AKG) on various cancers have shown its inhibitory effect on some cancers. Here, the effect of AKG on the proliferation and migration of 4T1 breast cancer cells was investigated. Methods: 4T1 cells were treated with different concentrations of AKG, the cell viability was calculated using the MTT test, and 160 μM of AKG was selected. 4T1 cells were cultured in the presence and absence 160 μM AKG, and the growth of 4T1 cells, population doubling time, colony forming potential, cell cycle profile and cell migration rate were investigated. Result and discussion: The results showed that AKG reduces the growth of 4T1 cells and increases the population doubling time in the treatment group compared to the control group. Also, AKG decreased the colony forming potential of 4T1 cells (in terms of colony number and size). AKG caused changes in the cell cycle profile in the treatment group, and the results of the scratch repair test also showed the effects of AKG in reducing the ability of cell migration in the treatment group compared to the control. The results of this study showed that AKG can reduce the survival and proliferation of breast cancer cells. It seems that the use of AKG along with other available treatments can help to control and treat breast cancer.

Keywords

Main Subjects

Abla, H., M. Sollazzo, G. Gasparre, L. Iommarini and A. M. Porcelli (2020). The multifaceted contribution of α-ketoglutarate to tumor progression: An opportunity to exploit? Seminars in cell & developmental biology, Elsevier.
Atlante, S., A. Visintin, E. Marini, M. Savoia, C. Dianzani, M. Giorgis, D. Sürün, F. Maione, F. Schnütgen and A. Farsetti (2018). "α-ketoglutarate dehydrogenase inhibition counteracts breast cancer-associated lung metastasis." Cell death & disease 9(7): 756.
Bray, F., J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre and A. Jemal (2018). "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries." CA: a cancer journal for clinicians 68(6): 394-424.
"Breast cancer—epidemiology, risk factors, classification, prognostic markers, and current treatment strategies—an updated review." Cancers 13(17): 4287.
Masoud, V. and G. Pagès (2017). "Targeted therapies in breast cancer: New challenges to fight against resistance." World journal of clinical oncology 8(2): 120.
Zdzisińska, B., Aleksandra ŻurekMartyna Kandefer-Szerszeń   (2017). "Alpha-ketoglutarate as a molecule with pleiotropic activity: well-known and novel possibilities of therapeutic use." Archivum immunologiae et therapiae experimentalis 65: 21-36.
Chin, R. M., X. Fu, M. Y. Pai, L. Vergnes, H. Hwang, G. Deng, S. Diep, B. Lomenick, V. S. Meli and G. C. Monsalve (2014). "The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR." Nature 510(7505): 397-401.
Harrison, A., M. Tygesen, B. Sawa-Wojtanowicz, S. Husted and M. Tatara (2004). "α-Ketoglutarate treatment early in postnatal life improves bone density in lambs at slaughter." Bone 35(1): 204-209.
Hu, X., Y. Liu, C. Qin, Z. Pan, J. Luo, A. Yu and Z. Cheng (2014). "Up-regulated isocitrate dehydrogenase 1 suppresses proliferation, migration and invasion in osteosarcoma: in vitro and in vivo." Cancer letters 346(1): 114-121.
Rzeski, W., K. Walczak, M. Juszczak, E. Langner, P. PoŻarowski, M. Kandefer-Szerszeń and S. G. Pierzynowski (2012). "Alpha-ketoglutarate (AKG) inhibits proliferation of colon adenocarcinoma cells in normoxic conditions." Scandinavian journal of gastroenterology 47(5): 565-571.
Sam Daliri, F., M. Talkhabi, N. Toolabi, F. Attari and M. Kehtari (2023). "Investigation of the Effect of Conditioned Media of Mesenchymal Stem Cells Treated with Ascorbic Acid on Proliferative Behavior of Breast Cancer Cells." Journal of Animal Biology 15(2): 233-245.
Sharifi, Z., M. Talkhabi and S. Taleahmad (2022). "Identification of potential microRNA diagnostic panels and uncovering regulatory mechanisms in breast cancer pathogenesis." Scientific Reports 12(1): 20135.
Sharma, G. N., R. Dave, J. Sanadya, P. Sharma and K. Sharma (2010). "Various types and management of breast cancer: an overview." Journal of advanced pharmaceutical technology & research 1(2): 109.
 "Alpha-Ketoglutarate and 5-HMF: A potential anti-tumoral combination against leukemia cells." Antioxidants 10(11): 1804.
"Supplementation with α-ketoglutarate improved the efficacy of anti-PD1 melanoma treatment through epigenetic modulation of PD-L1." Cell Death & Disease 14(2): 170.
Sica, V., J. M. Bravo-San Pedro, V. Izzo, J. Pol, S. Pierredon, D. Enot, S. Durand, N. Bossut, A. Chery and S. Souquere (2019). "Lethal poisoning of cancer cells by respiratory chain inhibition plus dimethyl α-ketoglutarate." Cell reports 27(3): 820-834. e829.
Sun, Y.-S., Z. Zhao, Z.-N. Yang, F. Xu, H.-J. Lu, Z.-Y. Zhu, W. Shi, J. Jiang, P.-P. Yao and H.-P. Zhu (2017). "Risk factors and preventions of breast cancer." International journal of biological sciences 13(11): 1387.
Tran, T. Q., E. A. Hanse, A. N. Habowski, H. Li, M. B. Ishak Gabra, Y. Yang, X. H. Lowman, A. M. Ooi, S. Y. Liao and R. A. Edwards (2020). "α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer." Nature cancer 1(3): 345-358.
Waks, A. G. and E. P. Winer (2019). "Breast cancer treatment: a review." Jama 321(3): 288-300.
Wu, N., M. Yang, U. Gaur, H. Xu, Y. Yao and D. Li (2016). "Alpha-ketoglutarate: physiological functions and applications." Biomolecules & therapeutics 24(1): 1.
Kaławaj, K., Katarzyna Kaławaj, Adrianna Sławińska-Brych, Magdalena Mizerska-Kowalska, Aleksandra Żurek, Agnieszka Bojarska-Junak, Martyna Kandefer-Szerszeń and Barbara Zdzisińska (2020). "Alpha ketoglutarate exerts in vitro anti-osteosarcoma effects through inhibition of cell proliferation, induction of apoptosis via the JNK and caspase 9-dependent mechanism, and suppression of TGF-β and VEGF production and metastatic potential of cells." International Journal of Molecular Sciences 21(24): 9406.