Vu Thi Thu, Ngo Thi Hai Yen

Main Article Content

Abstract

This study was conducted to evaluate the effect of Naringin (NAR) on multiple myeloma cells through assessment of cell proliferation and mitochondrial function. Methods: Human myeloma cell line (KMS-20) was subjected to normal (control) and treatment conditions. The viability, toxicity, cardiolipin content and mitochondrial membrane potential of KMS-20 cells in all groups were analyzed by using suitable kits. Results: The obtained data showed that NAR is toxic and inhibits the growth of KMS-20 cells. Similar to Doxorubicin (DOX)-treated cell group, the KMS-20 cell group supplemented with NAR had a sharp decrease in cardiolipin content compared to those in control group. The cardiolipin contents of KMS-20 cells in the DOX- and NAR-treated groups were 38.78±3.74 and 47.23±4.65 (% of control, p<0.05), respectively. In contrast to DOX, NAR strongly elevated the mitochondrial membrane potential of the KMS-20 cells. Conclusion:  This study shows that NAR has the ability to inhibit the growth of KMS-20 multiple myeloma celline by altering their mitochondrial structure and function.

Keywords: Naringin, KMS-20, mitochondria

References

[1] A. O. Ruiz, Y. R. Heredia, M. L. Morales, P. A. Garrido, A. G. Ortiz, A. Valeri, C. Bárcena,
R. M. G. Martin, V. Garrido, L. Moreno, A. Gimenez, M. Á. N. Aguadero, M. V. Estevez, E. Lospitao, M. T. Cedena, S. Barrio, J. M. López, M. Linares, M. Gallardo, Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma, Cancers, Vol. 13, No. 7, 2021, pp. 1662-số trang cuối, https://doi.org/10.3390/cancers13071662.
[2] K. Jöhrer, S. S. Ҫiҫek, Multiple Myeloma Inhibitory Activity of Plant Natural Products, Cancers, Vol. 13, No. 11, 2021, https://doi.org/10.3390/cancers13112678.
[3] I. S. Song, H. K. Kim, S. R. Lee, S. H. Jeong, N. Kim, K. S. Ko, B. D. Rhee, J. Han, Mitochondrial Modulation Decreases the Bortezomib-Resistance in Multiple Myeloma Cells. Int J. Cancer, Vol. 133, No. 6, 2013, pp. 1357-67, https://doi.org/10.1002/ijc.28149.
[4] K. A. Myriam E. Rodriguez, 1 Ping Zhang, 2 Song-mao Chiu, 1 Minh Lam, 4 Malcolm E. Kenney, 2, 5 Clemens Burda, 2, 3, 5 and Nancy L. Oleinick, Targeting of Mitochondria by 10-N-Alkyl Acridine Orange Analogues: Role of Alkyl Chain Length in Determining Cellular Uptake and Localization, Mitochondrion, Vol. 8, No. 3, 2008, pp. 237-246, https://doi.org/10.1016/j.mito.2008.04.003.
[5] M. C. Saiz, M. D. Busto, M. C. P. Izquierdo, N. Ortega, M. P. Mateos, P. Muniz, Antioxidant Properties, Radical Scavenging Activity and Biomolecule Protection Capacity of Flavonoid Naringenin and Its Glycoside Naringin: A Comparative Study, J. Sci Food Agric, Vol. 90,
No. 7, 2010, pp. 1238-44, https://doi.org/10.1002/jsfa.3959.
[6] M. Ikemura, Y. Sasaki, J.C. Giddings and J. Yamamoto, Preventive Effects of Hesperidin, Glucosyl Hesperidin and Naringin on Hypertension and Cerebral Thrombosis in Stroke-Prone Spontaneously Hypertensive Rats. Phytother Res,Vol. 26, No. 9, 2012, pp. 1272-7, https://doi.org/10.1002/ptr.3724.
[7] Y. Xiao, L.L. Li, Y.Y. Wang, J.J. Guo, W.P. Xu, Y.Y. Wang and Y. Wang, Naringin Administration Inhibits Platelet Aggregation and Release by Reducing Blood Cholesterol Levels and the Cytosolic Free Calcium Concentration in Hyperlipidemic Rabbits. Exp Ther Med,Vol. 8, No. 3, 2014, pp. 968-972, https://doi.org/10.3892/etm.2014.1794.
[8] O.A. Adebiyi, O.O. Adebiyi and P.M. Owira, Naringin Reduces Hyperglycemia-Induced Cardiac Fibrosis by Relieving Oxidative Stress. PLoS One,Vol. 11, No. 3, 2016, pp. e0149890, https://doi.org/10.1371/journal.pone.0149890.
[9] J.M. Assini, E.E. Mulvihill, A.C. Burke, B.G. Sutherland, D.E. Telford, S.S. Chhoker, C.G. Sawyez, M. Drangova, A.C. Adams, A. Kharitonenkov, C.L. Pin and M.W. Huff, Naringenin Prevents Obesity, Hepatic Steatosis, and Glucose Intolerance in Male Mice Independent of Fibroblast Growth Factor 21. Endocrinology,Vol. 156, No. 6, 2015, pp. 2087-2102, https://doi.org/10.1210/en.2014-2003.
[10] V. Thi Thu, N. T. H. Yen, Naringin Effectively Protects Cardiomyocytes against Hypoxia/Reoxygenation Injury, VNU Journal of Science: Natural Sciences and Technology, Vol. 37, No. 3, 2021, https://doi.org/10.25073/2588-1140/vnunst.5294.
[11] C. Y. Jian, H. B. Ouyang, X. H. Xiang, J. L. Chen, Y. X. Li, X. Zhou, J. Y. Wang, Y. Yang, E. Y. Zhong, W. H. Huang and H. W. Zhang, Naringin Protects Myocardial Cells from Doxorubicininduced Apoptosis Partially by Inhibiting the P38mapk Pathway, Mol Med Rep,Vol. 16, No. 6, 2017, pp. 9457-9463, https://doi.org/10.3892/mmr.2017.7823.
[12] E. Ramesh, A. A. Alshatwi, Naringin Induces Death Receptor and Mitochondria-Mediated Apoptosis in Human Cervical Cancer (Siha) Cells. Food and Chemical Toxicology, Vol. 51, 2013, pp. 97-105, https://doi.org/10.1016/j.fct.2012.07.033.
[13] S. Raha, S.M. Kim, H.J. Lee, S. Yumnam, V.V. Saralamma, S.E. Ha, W.S. Lee and G.S. Kim, Naringin Induces Lysosomal Permeabilization and Autophagy Cell Death in Ags Gastric Cancer Cells. Am J Chin Med,Vol. 48, No. 3, 2020, pp. 679-702, https://doi.org/10.1142/s0192415x20500342.
[14] H. Li, B. Yang, J. Huang, T. Xiang, X. Yin, J. Wan, F. Luo, L. Zhang, H. Li and G. Ren, Naringin Inhibits Growth Potential of Human Triple-Negative Breast Cancer Cells by Targeting Β-Catenin Signaling Pathway. Toxicol Lett,Vol. 220, No. 3, 2013, pp. 219-28, https://doi.org/10.1016/j.toxlet.2013.05.006.
[15] V.T. Thu, K.H. Kyu, L.T. Long, T.T. Thuy, B. Nyamaa, P.T. Bich, N. Kim and J. Han, Curcuminoids Suppress the Development of Kms-20 Cells Via Alterating Mitochondrial Function. Vietnam Journal of Physiology,Vol. 20, No. 2, 2016, pp. 1-9.
[16] L. Albuquerque de Oliveira Mendes, C.S. Ponciano, A.H. Depieri Cataneo, P.F. Wowk, J. Bordignon, H. Silva, M. Vieira de Almeida and E.P. Ávila, The Anti-Zika Virus and Anti-Tumoral Activity of the Citrus Flavanone Lipophilic Naringenin-Based Compounds. Chemico-Biological Interactions,Vol. 331, No., 2020, pp. 109218,
https://doi.org/10.1016/j.cbi.2020.109218.
[17] M. Ghanbari-Movahed, G. Jackson, M.H. Farzaei and A. Bishayee, A Systematic Review of the Preventive and Therapeutic Effects of Naringin against Human Malignancies. Frontiers in pharmacology,Vol. 12, No., 2021, pp. 639840-639840, https://doi.org/10.3389/fphar.2021.639840.
[18] V.T. Thu, N.T.H. Yen, N.H. Tung, P.T. Bich, J. Han and H.K. Kim, Majonoside-R2 Extracted from Vietnamese Ginseng Protects H9c2 Cells against Hypoxia/Reoxygenation Injury Via Modulating Mitochondrial Function and Biogenesis. Bioorg Med Chem Lett,Vol. 36, No., 2021, pp. 127814, https://doi.org/10.1016/j.bmcl.2021.127814.
[19] V.T. Thu, H.K. Kim, T. Long le, T.T. Thuy, N.Q. Huy, S.H. Kim, N. Kim, K.S. Ko, B.D. Rhee and J. Han, Necrox-5 Exerts Anti-Inflammatory and Anti-Fibrotic Effects Via Modulation of the Tnfα/Dcn/Tgfβ1/Smad2 Pathway in Hypoxia/Reoxygenation-Treated Rat Hearts. Korean J Physiol Pharmacol, Vol. 20, No. 3, 2016, pp. 305-14,
https://doi.org/10.4196/kjpp.2016.20.3.305.
[20] B. Pravin, V. Nanaware, B. Ashwini, ≪Em≫Insilico≪/Em≫ and ≪Em≫Invitro≪/Em≫ Optimization of Naringin and Rutin Molecules Targeting DNA Damage in Breast Cancer Cells. bioRxiv,Vol., No., 2021, pp. 2021.12.21.473577, https://doi.org/10.1101/2021.12.21.473577.
[21] O. P. M. Rodriguez, A. Gonzalez-Torres, L. M. A. Salas, H. Hernandez-Sanchez, B.E. Garcia-Perez, M.D.R. Thompson-Bonilla and M.E. Jaramillo-Flores, Effect of Naringenin and Its Combination with Cisplatin in Cell Death, Proliferation and Invasion of Cervical Cancer Spheroids. RSC Adv,Vol. 11, No. 1, 2020, pp. 129-141,
https://doi.org/10.1039/d0ra07309a.
[22] J. Willer, K. Jöhrer, R. Greil, C. Zidorn and S.S. Çiçek, Cytotoxic Properties of Damiana (Turnera Diffusa) Extracts and Constituents and a Validated Quantitative Uhplc-Dad Assay. Molecules,Vol. 24, No. 5, 2019,
https://doi.org/10.3390/molecules24050855.
[23] A. Palumbo, F. Gay, S. Bringhen, A. Falcone, N. Pescosta, V. Callea, T. Caravita, F. Morabito, V. Magarotto, M. Ruggeri, I. Avonto, P. Musto, N. Cascavilla, B. Bruno and M. Boccadoro, Bortezomib, Doxorubicin and Dexamethasone in Advanced Multiple Myeloma. Annals of Oncology,Vol. 19, No. 6, 2008, pp. 1160-1165, https://doi.org/10.1093/annonc/mdn018.
[24] M. P. Rossmann, S. M. Dubois, S. Agarwal, L. I. Zon, Mitochondrial Function in Development and Disease. Dis Model Mech, Vol. 14, No. 6, 2021, https://doi.org/10.1242/dmm.048912.
[25] J. Dudek, Role of Cardiolipin in Mitochondrial Signaling Pathways. Frontiers in Cell and Developmental Biology, Vol. 5, No. 90, 2017, https://doi.org/10.3389/fcell.2017.00090.
[26] G. Paradies, V. Paradies, F.M. Ruggiero, G. Petrosillo, Cardiolipin Alterations and Mitochondrial Dysfunction in Heart Ischemia/Reperfusion Injury. Clinical Lipidology,Vol. 10, No. 5, 2015, pp. 415-429, https://doi.org/10.2217/clp.15.31.
[27] M. A. Esmekaya, A. G. Canseven, H. Kayhan, M. Z. Tuysuz, B. Sirav, N. Seyhan, Mitochondrial Hyperpolarization and Cytochrome-C Release in Microwave-Exposed Mcf-7 Cells. Gen Physiol Biophys,Vol. 36, No. 2, 2017, pp. 211-218, https://doi.org/10.4149/gpb_2016021.
[28] X. Zhang, M. Fryknäs, E. Hernlund, W. Fayad, A. De Milito, M.H. Olofsson, V. Gogvadze, L. Dang, S. Påhlman, L.A.K. Schughart, L. Rickardson, P. D′Arcy, J. Gullbo, P. Nygren, R. Larsson and S. Linder, Induction of Mitochondrial Dysfunction as a Strategy for Targeting Tumour Cells in Metabolically Compromised Microenvironments. Nature Communications,Vol. 5, No. 1, 2014, pp. 3295, https://doi.org/10.1038/ncomms4295.