Inhibitory effects of salicylic acid on A549 human lung adenocarcinoma cell viability

Antiinflammatory drugs, such as salicylic acid and its metabolite acetylsalicylic acid, have been singled out as apoptosis-inducing agents with antitumoral activity. In addition, they reduce the risk of some cancers via an unclear mechanism. In this study, we have investigated the apoptotic, cytotoxic, and growth-inhibiting effects of salicylic acid on A549, the human lung adenocarcinoma, alveolar epithelial cells. Cytotoxicity was tested using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) colorimetric assay. We observed the ultrastructural and morphological changes in A549 cells by using transmission electron microscopy (TEM) and confocal microscopy. Cell viability was decreased by the optimal concentration (IC50) of 6.0 mM salicylic acid. Our TEM results showed cell structure damage and ultrastructural changes, concretely indicating apoptosis. With these results, the cytotoxic and potent antiproliferative effects of salicylic acid can be concluded to induce apoptosis in A549 cells.

Anahtar Kelimeler:

Salicylic acid, A549, apoptosis, cancer

Inhibitory effects of salicylic acid on A549 human lung adenocarcinoma cell viability

Keywords:

Salicylic acid, A549, apoptosis, cancer,

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Akre K, Ekstrom AM, Signorello LB, Hansson LE, Nyren O (2001). Aspirin and risk for gastric cancer: a population-based case- control study in Sweden. Br J Cancer 84: 965–968.
Antunes LMG, Barros R, Bueno L, Dias FL, Bianchi ML (2007). Acetylsalicylic acid exhibits anticlastogenic effects on cultured human lymphocytes exposed to doxorubicin. Mutat Res 626: 155–161.
Duan W, Zhang L (2006). Cyclooxygenase inhibitors not inhibit resting lung cancer A549 cell proliferation. Prostaglandins Leukot Essent Fatty Acids 74: 317–321.
Garcia-Heredia J, Hervas M, De la Rosa M, Navarro J (2008). Acetylsalicylic acid induces programmed cell death in Arabidopsis cell cultures. Planta 228: 89–97.
Ghobrial IM, Witzig TE, Adjei AA (2005). Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin 55: 178–194.
Giardiana C, Bourares H, Inan MS (1999). NSAIDs and butyrate sensitize a human colorectal cancer cell line to TNF-α and Fas ligation: the role of reactive oxygen species. Biochim Biophys Acta 3: 425–438.
Glass-Marmor L, Beitner R (1999). Taxol (paclitaxel) induces a detachment of phosphofructokinase from cytoskeleton of melanoma cells and decreases the levels of glucose 1,6-bisphosphate and ATP. Eur J Pharmacol 370: 195–199.
Gupta RA, DuBois RN (1998). Aspirin, NSAIDS, and colon cancer prevention: mechanisms? Gastroenterology 114: 1095–1098.
Hsieh CC, Hernandez-Ledesma B, de Lumen BO (2010). Lunasin, a novel peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact 186: 127–134.
Jacobs EJ, Thun MJ, Bain EB, Rodriguez C, Henley SJ, Calle EE (2007). A large cohort study of long-term daily use of adult- strength aspirin and cancer incidence. J Natl Cancer I 99: 608–615.
Jana NR (2008). NSAIDs and apoptosis. Cell Mol Life Sci 65: 1295– 1301.
Klessing DF, Malamy J (1994). The salicylic acid signal in plants. Plant Mol Biol 26: 1439–1458.
Lee I, Kolata A, Gewirtz A, Stolgen K (2000). Antitumor efficacy of the cytotoxic RNase, ranpirnase, on A549 human lung cancer xenografts of nude mice. Anticancer Res 27: 299–308.
Liu RH (2004). Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 134: 3479–3485.
Loll PJ, Picot D, Garavito RM (1995). The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase. Nat Struct Biol 2: 637–643.
Mao JT, Roth MD, Serio KJ, Baratelli F, Zhu L, Holmes EC, Strieter RM, Dubinett SM (2003). Celecoxib modulates the capacity for prostaglandin E2 and interleukin-10 production in alveolar macrophages from active smokers. Clin Cancer Res 9: 5835– 5841.
Mosmann T (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55–63.
Obradovic A, Zizic J, Trisovic N, Bozic J, Uscumlic G, Bozic B, Markovic S (2013). Evaluation of antioxidative effects of twelve 3-substituted-5,5-diphenylhydantoins on human colon cancer cell line HCT-116. Turk J Biol 37: 741–747.
Orosz F, Vertessy BG, Salerno C, Crifo C, Capuozzo E, Ovadi J (1997). The interaction of a new anti-tumor drug, KAR-2 with calmodulin. Brit J Pharmacol 121: 955–962.
Özkan A, Erdoğan A (2013). Membrane and DNA damaging/ protective effects of eugenol, eucalyptol, terpinen-4-ol, and camphor at various concentrations on parental and drug- resistant H1299 cells. Turk J Biol 37: 405–413.
Schildkraut JM, Moorman PG, Halabi S, Calingaert B, Marks JR, Berchuck A (2006). Analgesic drug use and risk of ovarian cancer. Epidemiology 17: 104–107.
Schreinemachers DM, Everson RB (1994). Aspirin use and lung, colon and breast cancer incidence in a prospective study. Epidemiology 5: 138–146.
Spitz GA, Furtado, CM, Sola-Penno M, Zancan P (2009). Acetylsalicylic acid and salicylic acid decrease tumor cell viability and glucose metabolism modulating 6-phosphofructo- 1-kinase structure and activity. Biochem Pharmacol 77: 46–53.
Suzuki Y, Inoue T, Ra C (2010). NSAIDs, mitochondria and calcium signaling: special focus on aspirin/salicylates. Pharmaceuticals 3: 1594–1613.
Tedeger I, Pfeilschifter J, Geisslinger G (2005). Cyclooxygenase- independent actions of cyclooxygenase inhibitors. FASEB J 15: 2057–2072.
Thun MJ, Henley SJ, Patrono C (2002). Nonsteroidal anti- inflammatory drugs as anticancer agents: mechanistic, pharmacologic and clinical issues. J Natl Cancer I 94: 252–266.
Urlich CM, Bigler J, Potter JD (2006). Non-steroidal anti- inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer 6: 130–140.