Abstract
Objectives
We evaluated the potential effects of aspirin combined with vitamin D3 on cell proliferation and apoptosis in oral cancer cells.
Results
Compared to the untreated control or individual drug, the combinations of aspirin and vitamin D3 significantly decreased the rates of cell proliferation by CCK-8 assay, and caused higher rates of cell apoptosis in both CAL-27 and SCC-15 cells by Annexin V-FITC apoptosis assay and flow cytometry. Remarkably, the combined treatment with aspirin and vitamin D3 significantly suppressed the expression of Bcl-2 protein and p-Erk1/2 protein, examined by western blot analysis.
Conclusions
Our study demonstrates that aspirin and vitamin D3 have biological activity against two human OSCC cell lines and their activity is synergistic or additive when two drugs used in combination with therapeutic concentrations. The combination of aspirin and vitamin D3 may be an effective approach for inducing cell death in OSCC.
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References
Abd Rahman F, Mohd Ali J, Abdullah M, Abu Kasim NH, Musa S (2016) Aspirin enhances osteogenic potential of periodontal ligament stem cells (PDLSCs) and modulates the expression profile of growth factor-associated genes in PDLSCs. J Periodontol 87:837–847
Cardus A, Parisi E, Gallego C, Aldea M, Fernandez E, Valdivielso JM (2006) 1,25-Dihydroxyvitamin D3 stimulates vascular smooth muscle cell proliferation through a VEGF-mediated pathway. Kidney Int 69:1377–1384
Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR, Dunlop MG (2012) Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology 142(1504–15):e3
El Abu Maaty MA, Wolfl S (2017) Effects of 1,25(OH)(2)D(3) on cancer cells and potential applications in combination with established and putative anti-cancer agents. Nutrients 9(1):87
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386
Fischel JL, Formento P, Milano G (2005) Epidermal growth factor receptor double targeting by a tyrosine kinase inhibitor (Iressa) and a monoclonal antibody (Cetuximab). Impact on cell growth and molecular factors. Br J Cancer 92:1063–1068
Krishnan AV, Moreno J, Nonn L, Malloy P, Swami S, Peng L, Peehl DM, Feldman D (2007) Novel pathways that contribute to the anti-proliferative and chemopreventive activities of calcitriol in prostate cancer. J Steroid Biochem Mol Biol 103:694–702
Liao D, Zhong L, Duan T, Zhang RH, Wang X, Wang G, Hu K, Lv X, Kang T (2015) Aspirin suppresses the growth and metastasis of osteosarcoma through the NF-kappaB pathway. Clin Cancer Res 21:5349–5359
Orell-Kotikangas H, Schwab U, Osterlund P, Saarilahti K, Makitie O, Makitie AA (2012) High prevalence of vitamin D insufficiency in patients with head and neck cancer at diagnosis. Head Neck 34:1450–1455
Park IS, Jo JR, Hong H, Nam KY, Kim JB, Hwang SH, Choi MS, Ryu NH, Jang HJ, Lee SH, Kim CS, Kwon TG, Park GY, Park JW, Jang BC (2010) Aspirin induces apoptosis in YD-8 human oral squamous carcinoma cells through activation of caspases, down-regulation of Mcl-1, and inactivation of ERK-1/2 and AKT. Toxicol In Vitro 24:713–720
Pommergaard HC, Burcharth J, Rosenberg J, Raskov H (2013a) Chemoprevention with acetylsalicylic acid, vitamin D and calcium reduces risk of carcinogen-induced lung tumors. Anticancer Res 33:4767–4770
Pommergaard HC, Burcharth J, Rosenberg J, Raskov H (2013b) Oral chemoprevention with acetyl salicylic acid, vitamin D and calcium reduces the risk of tobacco carcinogen-induced bladder tumors in mice. Cancer Invest 31:490–493
Reddy KK (2013) Vitamin D level and basal cell carcinoma, squamous cell carcinoma, and melanoma risk. J Invest Dermatol 133:589–592
Siegel RL, Miller KD, Jemal A (2017) Cancer Statistics, 2017. CA Cancer J Clin 67:7–30
Trump DL, Deeb KK, Johnson CS (2010) Vitamin D: considerations in the continued development as an agent for cancer prevention and therapy. Cancer J 16:1–9
Wang X, Diao Y, Liu Y, Gao N, Gao D, Wan Y, Zhong J, Jin G (2015) Synergistic apoptosis-inducing effect of aspirin and isosorbide mononitrate on human colon cancer cells. Mol Med Rep 12:4750–4758
Wilson JC, Anderson LA, Murray LJ, Hughes CM (2011) Non-steroidal anti-inflammatory drug and aspirin use and the risk of head and neck cancer: a systematic review. Cancer Causes Control 22:803–810
Yue W, Zheng X, Lin Y, Yang CS, Xu Q, Carpizo D, Huang H, DiPaola RS, Tan XL (2015) Metformin combined with aspirin significantly inhibit pancreatic cancer cell growth in vitro and in vivo by suppressing anti-apoptotic proteins Mcl-1 and Bcl-2. Oncotarget 6:21208–21224
Zhong W, Gu B, Gu Y, Groome LJ, Sun J, Wang Y (2014) Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in endothelial cells. J Steroid Biochem Mol Biol 140:56–62
Acknowledgement
This study was financially supported by the Program for Innovation Team Building at Institutions of Higher Education in Chongqing in 2016 (NO CXTDG201602006), the Scientific and Technological Research Program of Health and Family planning Commission of Chongqing Province (2017ZDXM019), and Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education.
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Xiao, TT., Li, X., Feng, JL. et al. Combined effects of aspirin and vitamin D3 on two OSCC cell lines: a preliminary study. Biotechnol Lett 40, 551–559 (2018). https://doi.org/10.1007/s10529-018-2508-5
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DOI: https://doi.org/10.1007/s10529-018-2508-5