Synergistic Effect of Caffeine in B16f10 Cells in Combination with Doxorubicin and Oxaliplatin
DOI:
https://doi.org/10.18311/ti/2023/v30i2/33205Keywords:
Anticancer Therapy, Chemotherapy, Melanoma, Xanthine AlkaloidsAbstract
Caffeine is a commonly consumed psychoactive substance that has been shown to have various effects on cellular processes, including cell growth and survival. In this study, we investigated the potential of Caffeine to enhance the cytotoxic effects of two commonly used chemotherapeutic agents, doxorubicin and oxaliplatin, on B16F10 cells. We evaluated the cytotoxicity, calculated the IC50 and combination index of the medications, estimated the cell cycle of the cells, and evaluated the apoptotic and anti-apoptotic genes through gene expression analysis. Our results demonstrated that Caffeine significantly potentiated the cytotoxicity of both doxorubicin and oxaliplatin, resulting in a more significant reduction in cell viability compared to treatment with the chemotherapeutic agents alone. Additionally, Caffeine also enhanced the pro-apoptotic effects of the chemotherapeutic agents, leading to increased levels of apoptosis in the B16F10 cells. The combination of doxorubicin and oxaliplatin with Caffeine was found to be synergistic. These findings suggest that caffeine may have the potential to improve the efficacy of current chemotherapeutic regimens and may offer a novel approach to enhance cancer treatment.
Downloads
Published
How to Cite
Issue
Section
Accepted 2023-03-28
Published 2023-05-11
References
Mîndrilă I, Osman A, Mîndrilă B, Predoi MC, Mihaiescu DE, Buteică SA. Phenotypic Switching of B16F10 Melanoma cells as a stress adaptation response to fe3o4/salicylic acid nanoparticle therapy. Pharmaceuticals. 2021; 14(10):1007. https://doi.org/10.3390/ph14101007 PMid:34681232 PMCid:PMC8537856 DOI: https://doi.org/10.3390/ph14101007
Schirrmacher V. From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review). Int J Oncol. 2019; 54(2):407-419. https://doi.org/10.3892/ijo.2018.4661 PMid:30570109 PMCid:PMC6317661 DOI: https://doi.org/10.3892/ijo.2018.4661
Alcindor T, Beauger N. Oxaliplatin: A review in the era of molecularly targeted therapy. Curr Oncol. 2011; 18(1):18- 25. https://doi.org/10.3747/co.v18i1.708 PMid:21331278 PMCid:PMC3031353 DOI: https://doi.org/10.3747/co.v18i1.708
Peter S, Alven S, Maseko RB, Aderibigbe BA. Doxorubicinbased hybrid compounds as potential anticancer agents: A review. Molecules. 2022; 27(14). https://doi.org/10.3390/ molecules27144478 PMid:35889350 PMCid:PMC9318127 DOI: https://doi.org/10.3390/molecules27144478
Sc Y, Muralidhara. Beneficial role of coffee and caffeine in neurodegenerative diseases: A minireview. AIMS public Heal. 2016; 3(2):407-422. https://doi.org/10.3934/publichealth. 2016.2.407 PMid:29546172 PMCid:PMC5690364 DOI: https://doi.org/10.3934/publichealth.2016.2.407
Liu H, Hu GH, Wang XC, et al. Coffee consumption and prostate cancer risk: A meta-analysis of cohort studies. Nutr Cancer. 2015; 67(3):392-400. https://doi.org/10.1080 /01635581.2015.1004727 PMid:25706900 DOI: https://doi.org/10.1080/01635581.2015.1004727
Wu S, Han J, Song F, et al. Caffeine intake, coffee consumption, and risk of cutaneous malignant melanoma. Epidemiology. 2015; 26(6):898-908. https:// doi.org/10.1097/EDE.0000000000000360 PMid:26172864 PMCid:PMC4600068 DOI: https://doi.org/10.1097/EDE.0000000000000360
Yew YW, Lai YC, Schwartz RA. Coffee consumption and melanoma: A systematic review and meta-analysis of observational studies. Am J Clin Dermatol. 2016; 17(2):113- 123. https://doi.org/10.1007/s40257-015-0165-1 PMid:26547919 DOI: https://doi.org/10.1007/s40257-015-0165-1
Yang H, Rouse J, Lukes L, et al. Caffeine suppresses metastasis in a transgenic mouse model: A prototype molecule for prophylaxis of metastasis. Clin Exp Metastasis. 2005; 21(8):719-735. https://doi.org/10.1007/s10585-004-8251-4 PMid:16035617 DOI: https://doi.org/10.1007/s10585-004-8251-4
Gude RP, Menon LG, Rao SGA. Effect of caffeine, a xanthine derivative, in the inhibition of experimental lung metastasis induced by B16F10 melanoma cells. J Exp Clin Cancer Res. 2001; 20(2):287-292.
Belizariol JE, Tilly JL, Sherwood SW. Caffeine potentiates the lethality of tumour necrosis factor in cancer cells. Br J Cancer. 1993; 67(6):1229-1235. https://doi.org/10.1038/ bjc.1993.230 PMid:8512808 PMCid:PMC1968497 DOI: https://doi.org/10.1038/bjc.1993.230
Ku BM, Lee YK, Jeong JY, et al. Caffeine inhibits cell proliferation and regulates PKA/GSK3β pathways in U87MG human glioma cells. Mol Cells. 2011; 31(3):275-279. https:// doi.org/10.1007/s10059-011-0027-5 PMid:21229324 PMCid:PMC3932700 DOI: https://doi.org/10.1007/s10059-011-0027-5
Dalvi RR. Acute and chronic toxicity of caffeine: A review. Vet Hum Toxicol. 1986; 28(2):144-150.
Nomura M, Tsukada H, Ichimatsu D, Ito H, Yoshida T, Miyamoto KI. Inhibition of epidermal growth factorinduced cell transformation by tannins. Phytochemistry. 2005; 66(17 SPEC. ISS.):2038-2046. https://doi. org/10.1016/j.phytochem.2005.01.018 PMid:16153407 DOI: https://doi.org/10.1016/j.phytochem.2005.01.018
Dong S, Kong J, Kong J, et al. Low concentration of caffeine inhibits the progression of the hepatocellular carcinoma via akt signaling pathway. Anticancer Agents Med Chem. 2015; 15(4):484-492. https://doi.org/10.2174/1871520615666150 209110832 PMid:25666502 DOI: https://doi.org/10.2174/1871520615666150209110832
Li A, Wu N, Zou H, Zhu B, Xiong S, Xiao G. Low concentration of caffeine inhibits cell viability, migration and invasion, and induces cell apoptosis of B16F10 melanoma cells. Int J Clin Exp Pathol. 2016; 9(11):11206-11213.
Kajstura M, Halicka HD, Pryjma J, Darzynkiewicz Z. Discontinuous fragmentation of nuclear DNA during apoptosis revealed by discrete “Sub-G1” peaks on DNA content histograms. Cytom Part A. 2007; 71(3):125-131. https://doi.org/10.1002/cyto.a.20357 PMid:17252584 DOI: https://doi.org/10.1002/cyto.a.20357
Ahmed B, Qadir MI, Ghafoor S. Malignant melanoma: Skin cancer- diagnosis, prevention, and treatment. Crit Rev Eukaryot Gene Expr. 2020; 30(4):291-297. https:// doi.org/10.1615/CritRevEukaryotGeneExpr. 2020028454 PMid:32894659 DOI: https://doi.org/10.1615/CritRevEukaryotGeneExpr.2020028454
van den Boogaard WMC, Komninos DSJ, Vermeij WP. Chemotherapy side-effects: Not all DNA damage is equal. Cancers (Basel). 2022; 14(3):627. https://doi.org/10.3390/ cancers14030627 PMid:35158895 PMCid:PMC8833520 DOI: https://doi.org/10.3390/cancers14030627
Bode AM, Dong Z. The enigmatic effects of caffeine in cell cycle and cancer. Cancer Lett. 2007; 247(1-2):26-39. https:// doi.org/10.1016/j.canlet.2006.03.032 PMid:16709440 PMCid:PMC2824565
Cappelletti S, Daria P, Sani G, Aromatario M. Caffeine: Cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol. 2014; 13(1): 71-88. https:// doi.org/10.2174/1570159X13666141210215655 PMid: 26074744 PMCid:PMC4462044 DOI: https://doi.org/10.2174/1570159X13666141210215655
Liu H, Zhou Y, Tang L. Caffeine induces sustained apoptosis of human gastric cancer cells by activating the caspase-9/ caspase-3 signalling pathway. Mol Med Rep. 2017; 16(3):2445-2454. https://doi.org/10.3892/mmr.2017.6894 PMid:28677810 PMCid:PMC5547974 DOI: https://doi.org/10.3892/mmr.2017.6894
Mokhtari RB, Homayouni TS, Baluch N, et al. Combination therapy in combating cancer. Oncotarget. 2017; 8(23):38022-38043. https://doi.org/10.18632/oncotarget. 16723 PMid:28410237 PMCid:PMC5514969 DOI: https://doi.org/10.18632/oncotarget.16723
Jafari S, Lavasanifar A, Hejazi MS, Maleki-Dizaji N, Mesgari M, Molavi O. STAT3 inhibitory stattic enhances immunogenic cell death induced by chemotherapy in cancer cells. DARU, J Pharm Sci. 2020; 28(1):159-169. https:// doi.org/10.1007/s40199-020-00326-z PMid:31942696 PMCid:PMC7214602 DOI: https://doi.org/10.1007/s40199-020-00326-z
Mittal A, Tabasum S, Singh RP. Berberine in combination with doxorubicin suppresses growth of murine melanoma B16F10 cells in culture and xenograft. Phytomedicine. 2014; 21(3):340-347. https://doi.org/10.1016/j.phymed. 2013.09.002 PMid:24176840 DOI: https://doi.org/10.1016/j.phymed.2013.09.002
Higuchi T, Kawaguchi K, Miyake K, et al. Oral recombinant methioninase combined with caffeine and doxorubicin induced regression of a doxorubicin-resistant synovial sarcoma in a PDOX mouse model. Anticancer Res. 2018; 38(10):5639-5644. https://doi.org/10.21873/anticanres. 12899 PMid:30275182 DOI: https://doi.org/10.21873/anticanres.12899
Lu PZ, Lai CY, Wen-Hsiung C. Caffeine induces cell death via activation of apoptotic signal and inactivation of survival signal in human osteoblasts. Int J Mol Sci. 2008; 9(5):698- 718. https://doi.org/10.3390/ijms9050698 PMid:19325779 PMCid:PMC2635715 DOI: https://doi.org/10.3390/ijms9050698
Hashimoto T, He Z, Ma WY, et al. Caffeine inhibits cell proliferation by G0/G1 phase arrest in JB6 cells. Cancer Res. 2004; 64(9):3344-3349. https://doi.org/10.1158/0008-5472.CAN-03-3453 PMid:15126379 DOI: https://doi.org/10.1158/0008-5472.CAN-03-3453
Bode AM, Dong Z. The enigmatic effects of caffeine in cell cycle and cancer. Cancer Lett. 2007; 247(1):26-39. https:// doi.org/10.1016/j.canlet.2006.03.032 PMid:16709440 PMCid:PMC2824565 DOI: https://doi.org/10.1016/j.canlet.2006.03.032
Dubrez L, Coll JL, Hurbin A, Solary E, Favrot MC. Caffeine sensitizes human H358 cell line to p53-mediated apoptosis by inducing mitochondrial translocation and conformational change of BAX protein. J Biol Chem. 2001; 276(42):38980-38987. https://doi.org/10.1074/jbc. M102683200 PMid:11489880 DOI: https://doi.org/10.1074/jbc.M102683200