Effects of Curcumin Treatment on Cell Energy Status, Levels of Mitochondrial Enzymes, and Gene Expression of Glucose-related Mechanism in Pancreatic Cancer Cell Lines

Yıl 2023, Cilt: 7 Sayı: 3, 70 - 84, 30.09.2023

Emine Nedime Korucu Esma Menevşe Dudu Erkoç Kaya Fatma Gokturk Hilal Arikoglu

https://doi.org/10.30621/jbachs.1180856

Öz

Background and Purpose:. Curcumin is an active component of turmeric, has antitumor, immunomodulatory, anti-inflammatory effects. It was aimed to investigate the effects of the administration of curcumin on the energy metabolism, the abnormal redox defense mechanism profile, the malignant transformation indicator of Panc-1 and BxPC-3 pancreatic cancer cells.
Methods: BxPC-3 and Panc-1 cells were incubated, were replaced with containing various concentrations of curcumin (10-125 μM) for 24 h. Cell lysate Adenosine triphosphate (ATP), Adenosine diphosphate (ADP), Adenosine monophosphate (AMP), Manganese superoxidase (MnSOD), and cytochrome p450 reductase (CPR) concentrations were analyzed with HPLC and ELISA methods. Genes expression of Lactate dehydrogenase (LDH), mitochondrially encoded ATP synthase membrane subunit 6 (MTATP6), Glucose transporter 1 (GLUT1), and cytochrome p450 were analyzed.
Results and Conclusion: IC50 values for 24 hours were found as 47,26 μM in BxPC-3 and 45,84 μM in Panc-1 cells. Treatment with curcumin inhibits oxidative stress by increasing MnSOD enzyme levels. ATP levels did not change in BxPC-3 cells, but it showed an increase in Panc-1 supplemented with curcumin. The effects of curcumin on GLUT-1 are significantly important at a dose of curcumin of 45 μM concentration and affect glucose consumption in both cells. Curcumin showed anti-proliferative, and antioxidant effects.

Anahtar Kelimeler

Panc-1, BxPC-3, curcumin, MnSOD, ATP, CPR

Destekleyen Kurum

Necmettin Erbakan University Scientific Research Coordinator

Proje Numarası

181215004

Kaynakça

• Reference 1. Siegel RL, Miller KD, Jemal A. Cancer statistics. CA: a cancer journal for clinicians. 2019;69(1):7-34.
• Reference 2. Oettle H. Progress in the knowledge and treatment of advanced pancreatic cancer: from benchside to bedside. Cancer Treat Rev. 2014;40(9):1039-47.
• Reference 3. Pierson JT, Dietzgen RG, Shaw PN, Roberts‐Thomson SJ, Monteith GR, Gidley MJ. Major Australian tropical fruits biodiversity: Bioactive compounds and their bioactivities. Mol Nutr Food Res. 2012;56(3):357-87.
• Reference 4. Girardelo JR, Munari EL, Dallorsoleta JC, et al. Bioactive compounds, antioxidant capacity and antitumoral activity of ethanolic extracts from fruits and seeds of Eugenia involucrata DC. Food Res Int. 2020;137:109615.
• Reference 5. Pavia M, Pileggi C, Nobile CG, Angelillo IF. Association between fruit and vegetable consumption and oral cancer: a meta-analysis of observational studies. Am J Clin Nutr. 2006;83(5):1126-34.
• Reference 6. Freedman N, Park Y, Subar A, et al. Fruit and vegetable intake and head and neck cancer in a large United States prospective cohort study. AACR; 2007.
• Reference 7. Dinkova-Kostova AT, Talalay P. Relation of structure of curcumin analogs to their potencies as inducers of Phase 2 detoxification enzymes. Carcinogenesis. 1999;20(5):911-4.
• Reference 8. Nakmareong S, Kukongviriyapan U, Pakdeechote P, et al. Tetrahydrocurcumin alleviates hypertension, aortic stiffening and oxidative stress in rats with nitric oxide deficiency. Hypertens Res. 2012;35(4):418-25.
• Reference 9. Suresh S, Yadav VR, Suresh A. Health benefits and therapeutic applications of curcumin. Clin Res Regul Aff. 2006;23(3-4):191-210.
• Reference 10. Zhang N, Li H, Jia J, He M. Anti-inflammatory effect of curcumin on mast cell-mediated allergic responses in ovalbumin-induced allergic rhinitis mouse. Cellular Immunol. 2015;298(1-2):88-95.
• Reference 11. Song X, Zhang M, Dai E, Luo Y. Molecular targets of curcumin in breast cancer. Mol Med Rep. 2019;19(1):23-9.
• Reference 12. Jantan I, Bukhari SNA, Lajis NH, Abas F, Wai LK, Jasamai M. Effects of diarylpentanoid analogues of curcumin on chemiluminescence and chemotactic activities of phagocytes. J Pharm Pharmacol. 2012;64(3):404-12.
• Reference 13. Trujillo J, Chirino YI, Molina-Jijón E, Andérica-Romero AC, Tapia E, Pedraza-Chaverrí J. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol. 2013;1(1):448-56.
• Reference 14. Kiso Y, Suzuki Y, Watanabe N, Oshima Y, Hikino H. Antihepatotoxic principles of Curcuma longa rhizomes. Planta Med. 1983;49(11):185-7.
• Reference 15. Fujiwara H, Hosokawa M, Zhou X, et al. Curcumin inhibits glucose production in isolated mice hepatocytes. Diabetes Res Clin Pr. 2008;80(2):185-91.
• Reference 16. Zhu L, Ding X, Zhang D, Ch Y, Wang J, Ndegwa E, et al. Curcumin inhibits bovine herpesvirus type 1 entry into MDBK cells. Acta Virol. 2015;59(3):221-7.
• Reference 17. Seitz HK, Stickel F. Molecular mechanisms of alcohol-mediated carcinogenesis. Nat Rev Cancer. 2007;7(8):599-612.
• Reference 18. McFadyen MC, Melvin WT, Murray GI. Cytochrome P450 enzymes: novel options for cancer therapeutics. Mol Cancer Ther. 2004;3(3):363-71.
• Reference 19. Zhou S, Chan E, Li X, Huang M. Clinical outcomes and management of mechanism-based inhibition of cytochrome P450 3A4. Ther Clin Risk Manag. 2005;1(1):3.
• Reference 20. Drobná Z, Walton FS, Harmon AW, Thomas DJ, Stýblo M. Interspecies differences in metabolism of arsenic by cultured primary hepatocytes. Toxicol Appl Pharmacol. 2010;245(1):47-56.
• Reference 21. Wang S-M, Zhu A-P, Li D, Wang Z, Zhang P, Zhang G-L. Frequencies of genotypes and alleles of the functional SNPs in CYP2C19 and CYP2E1 in mainland Chinese Kazakh, Uygur and Han populations. J Hum Genet. 2009;54(6):372-5.
• Reference 22. Cederbaum AI. Role of CYP2E1 in ethanol-induced oxidant stress, fatty liver and hepatotoxicity. Dig Dis. 2010;28(6):802-11.
• Reference 23. Linhart K, Bartsch H, Seitz HK. The role of reactive oxygen species (ROS) and cytochrome P-450 2E1 in the generation of carcinogenic etheno-DNA adducts. Redox Biol. 2014;3:56-62.
• Reference 24. Maksymchuk O, Shysh A, Rosohatska I, Chashchyn M. Quercetin prevents type 1 diabetic liver damage through inhibition of CYP2E1. Pharmacol Rep. 2017;69(6):1386-92.
• Reference 25. Kawahara B, Faull KF, Janzen C, Mascharak PK. Carbon Monoxide Inhibits Cytochrome P450 Enzymes CYP3A4/2C8 in Human Breast Cancer Cells, Increasing Sensitivity to Paclitaxel. J Med Chem. 2021.
• Reference 26. Warburg O. On the origin of cancer cells. Science (New York, NY). 1956;123(3191):309-14.
• Reference 27. Manka D, Millhorn DE. A potential molecular link between aerobic glycolysis and cancer. Cell cycle (Georgetown, Tex). 2006;5(4):343-4.
• Reference 28. Kallalli BN, Rawson K, Singh A, Awati MA, Shivhare P. Lactate dehydrogenase as a biomarker in oral cancer and oral submucous fibrosis. J Oral Pathol Med. 2016;45(9):687-90.
• Reference 29. Galber C, Acosta MJ, Minervini G, Giorgio V. The role of mitochondrial ATP synthase in cancer. Biological chemistry. 2020;401(11):1199-214.
• Reference 30. Shim BY, Jung J-H, Lee K-M, et al. Glucose transporter 1 (GLUT1) of anaerobic glycolysis as predictive and prognostic values in neoadjuvant chemoradiotherapy and laparoscopic surgery for locally advanced rectal cancer. Int J Colorectal Dis. 2013;28(3):375-83.
• Reference 31. Ancey PB, Contat C, Meylan E. Glucose transporters in cancer–from tumor cells to the tumor microenvironment. The FEBS J. 2018;285(16):2926-43.
• Reference 32. Chiche J, Brahimi‐Horn MC, Pouysségur J. Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer. J Cell Mol Med. 2010;14(4):771-94.
• Reference 33. Pragallapati S, Manyam R. Glucose transporter 1 in health and disease. Journal of oral and maxillofacial pathology: JOMFP. 2019;23(3):443.
• Reference 34. Gurudath S, Naik RM, Ganapathy K, Guruprasad Y, Sujatha D, Pai A. Superoxide dismutase and glutathione peroxidase in oral submucous fibrosis, oral leukoplakia, and oral cancer: A comparative study. J Orof Sci. 2012;4(2):114.
• Reference 35. Che M, Wang R, Li X, Wang H-Y, Zheng XS. Expanding roles of superoxide dismutases in cell regulation and cancer. Drug Discov Today. 2016;21(1):143-9.
• Reference 36. Szabó C, Saunders C, O'Connor M, Salzman AL. Peroxynitrite causes energy depletion and increases permeability via activation of poly (ADP-ribose) synthetase in pulmonary epithelial cells. Am J Respir Cell Mol Biol. 1997;16(2):105-9.
• Reference 37. Bu F, Zhu X, Yi X, et al. Expression Profile of GINS Complex Predicts the Prognosis of Pancreatic Cancer Patients. OncoTargets Ther. 2020;13:11433.
• Reference 38. Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19(8):649-58.
• Reference 39. Liao H, Wang Z, Deng Z, Ren H, Li X. Curcumin inhibits lung cancer invasion and metastasis by attenuating GLUT1/MT1-MMP/MMP2 pathway. Int J Clin Exp Med. 2015;8(6):8948.
• Reference 40. Moghadam AA, Ebrahimie E, Taghavi SM, et al. How the nucleus and mitochondria communicate in energy production during stress: nuclear MtATP6, an early-stress responsive gene, regulates the mitochondrial F1F0-ATP synthase complex. Mol Biotechnol. 2013;54(3):756-69.
• Reference 41. Hsu P-H, Chen W-H, JuanLu C, Hsieh S-C, Lin S-C, Mai R-T, et al. Hesperidin and Chlorogenic Acid Synergistically Inhibit the Growth of Breast Cancer Cells via Estrogen Receptor/Mitochondrial Pathway. Life. 2021;11(9):950.
• Reference 42. Galber C, Acosta MJ, Minervini G, Giorgio VJBC. The role of mitochondrial ATP synthase in cancer. Biol Chem. 2020;401(11):1199-214.
• Reference 43. Dijk SN, Protasoni M, Elpidorou M, Kroon AM, Taanman J-W. Mitochondria as target to inhibit proliferation and induce apoptosis of cancer cells: The effects of doxycycline and gemcitabine. Sci Rep. 2020;10(1):1-15.
• Reference 44. Matsui Y, Kitade H, Kamiya T, et al. Adenylate energy charge of rat and human cultured hepatocytes. In Vitro Cell Dev Biol Anim. 1994;30(9):609-14.
• Reference 45. Ma M, Ma C, Li P, et al. Low glucose enhanced metformin’s inhibitory effect on pancreatic cancer cells by suppressing glycolysis and inducing energy stress via up-regulation of miR-210-5p. Cell Cycle (Georgetown, Tex). 2020;19(17):2168-81.
• Reference 46. Liu Y-x, Feng J-y, Sun M-m, et al. Aspirin inhibits the proliferation of hepatoma cells through controlling GLUT1-mediated glucose metabolism. Acta Pharm Sinic. 2019;40(1):122-32.
• Reference 47. Melstrom LG, Salabat MR, Ding X-Z, et al. Apigenin down-regulates the hypoxia response genes: HIF-1α, GLUT-1, and VEGF in human pancreatic cancer cells. J Surg Res. 2011;167(2):173-81.
• Reference 48. Abouzeid AH, Patel NR, Rachman IM, Senn S, Torchilin VP. Anti-cancer activity of anti-GLUT1 antibody-targeted polymeric micelles co-loaded with curcumin and doxorubicin. J Drug Targeting. 2013;21(10):994-1000.
• Reference 49. Sur S, Nakanishi H, Flaveny C, et al. Inhibition of the key metabolic pathways, glycolysis and lipogenesis, of oral cancer by bitter melon extract. Cell Commun Signal. 2019;17(1):1-13.
• Reference 50. Fu Z, Cao X, Liu L, et al. Genistein inhibits lung cancer cell stem‑like characteristics by modulating MnSOD and FoxM1 expression. Oncol Lett. 2020;20(3):2506-15.
• Reference 51. Hao F, Kang J, Cao Y,et al. Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic β-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways. Apoptosis : an international journal on programmed cell death. 2015;20(11):1420-32.
• Reference 52. Schiffman SC, Li Y, Martin RC. The association of manganese superoxide dismutase expression in barrett's esophageal progression with MnTBAP and curcumin oil therapy. J Surg Res. 2012;176(2):535-41.
• Reference 53. Cao X, Liu L, Yuan Q, et al. Isovitexin reduces carcinogenicity and stemness in hepatic carcinoma stem-like cells by modulating MnSOD and FoxM1. J Exp Clin Canc Res. 2019;38(1):1-18.
• Reference 54. Qiu Y, Cao X, Liu L, et al. Modulation of MnSOD and FoxM1 is involved in invasion and EMT suppression by isovitexin in hepatocellular carcinoma cells. Cancer Manage Res. 2020;12:5759.
• Reference 55. Wei X, Xu Y, Xu FF, et al. RelB expression determines the differential effects of ascorbic acid in normal and cancer cells. Cancer Res. 2017;77(6):1345-56.
• Reference 56. Patel SA, Bhambra U, Charalambous MP, et al. Interleukin-6 mediated upregulation of CYP1B1 and CYP2E1 in colorectal cancer involves DNA methylation, miR27b and STAT3. Brit J Cancer. 2014;111(12):2287-96.
• Reference 57. Vaclavikova R, Hubackova M, Stribrna-Sarmanova J, et al. RNA expression of cytochrome P450 in breast cancer patients. Anticancer Res. 2007;27(6C):4443-50.
• Reference 58. Sakurai K, Enomoto K, Matsuo S, Amano S, Shiono M. CYP3A4 expression to predict treatment response to docetaxel for metastasis and recurrence of primary breast cancer. Surg Today. 2011;41(5):674-9.
• Reference 59. Quah SY, Chin JH, Akowuah GA, Khalivulla SI, Yeong SW, Sabu MC. Cytotoxicity and cytochrome P450 inhibitory activities of Clinacanthus nutans. Drug Metab Pers Ther. 2017;32(1):59-65.