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Published in: Tumor Biology 5/2014

01-05-2014 | Research Article

Efficacy of acetylsalicylic acid (aspirin) in skin B16-F0 melanoma tumor-bearing C57BL/6 mice

Authors: Nikhil M. Vad, Shashi K. Kudugunti, Hezhen Wang, G. Jayarama Bhat, Majid Y. Moridani

Published in: Tumor Biology | Issue 5/2014

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Abstract

Several epidemiological studies show that aspirin can act as a chemopreventive agent and decrease the incidences of various cancers including melanoma. In this work, we investigated the in vitro and in vivo efficacy of acetylsalicylic acid (ASA) as an antimelanoma agent in B16-F0 cells and skin B16-F0 melanoma tumor mouse model. Our findings indicate that the IC50 (48 h) for ASA in B16-F0 melanoma cells was 100 μM and that ASA caused a dose- and time-dependent GSH depletion and increase in reactive oxygen species (ROS) formation in B16-F0 melanoma cells. Male C57BL/6 mice were inoculated s.c. with 1 × 106 B16-F0 melanoma cells. ASA (80, 100, and 150 mg/kg) was initiated on day 1 or day 7, or day 9 after cell inoculation and continued daily for 13, 7, and 5 days, respectively. Animals were weighed daily and sacrificed on day 13. The tumors were excised and weighed. The animals receiving 13 days of ASA therapy at 80, 100, and 150 mg/kg demonstrated tumor growth inhibition by 1 ± 12 %, 19 ± 22 %, and 50 ± 29 %, respectively. Animals receiving 7 days of therapy at 80, 100, and 150 mg/kg demonstrated tumor growth inhibition by 12 ± 14 %, 27 ± 14 %, and 40 ± 14 %, respectively. No significant tumor growth inhibition was observed with 5 days of therapy. ASA at 100 and 150 mg/kg caused significant tumor growth inhibition in C57BL/6 mice when administered for 13 and 7 days, respectively. The results obtained in this study are consistent with the recent epidemiologically based report that aspirin is associated with lower melanoma risk in humans.
Literature
1.
go back to reference Saleem M, Maddodi N, Abu Zaid M, Khan N, Bin Hafeez B, Asim M, et al. Lupeol inhibits growth of highly aggressive human metastatic melanoma cells in vitro and in vivo by inducing apoptosis. Clin Cancer Res. 2008;14:2119–212. 14.CrossRefPubMed Saleem M, Maddodi N, Abu Zaid M, Khan N, Bin Hafeez B, Asim M, et al. Lupeol inhibits growth of highly aggressive human metastatic melanoma cells in vitro and in vivo by inducing apoptosis. Clin Cancer Res. 2008;14:2119–212. 14.CrossRefPubMed
3.
go back to reference Naish S, Cooksey C, Riley P. Initial mushroom tyrosinase-catalysed oxidation product of 4-hydroxyanisole is 4-methoxy-ortho-benzoquinone. Pigment Cell Res. 1988;1:379–81.CrossRefPubMed Naish S, Cooksey C, Riley P. Initial mushroom tyrosinase-catalysed oxidation product of 4-hydroxyanisole is 4-methoxy-ortho-benzoquinone. Pigment Cell Res. 1988;1:379–81.CrossRefPubMed
4.
go back to reference Naish S, Holden JL, Cooksey CJ, Riley PA. Major primary cytotoxic product of 4-hydroxyanisole oxidation by mushroom tyrosinase is 4-methoxy ortho benzoquinone. Pigment Cell Res. 1988;1:382–5.CrossRefPubMed Naish S, Holden JL, Cooksey CJ, Riley PA. Major primary cytotoxic product of 4-hydroxyanisole oxidation by mushroom tyrosinase is 4-methoxy ortho benzoquinone. Pigment Cell Res. 1988;1:382–5.CrossRefPubMed
5.
go back to reference Moridani MY, Cheon SS, Khan S, O’Brien PJ. Metabolic activation of 4-hydroxyanisole by isolated rat hepatocytes. Drug Metab Dispos. 2002;30:1063–9.CrossRefPubMed Moridani MY, Cheon SS, Khan S, O’Brien PJ. Metabolic activation of 4-hydroxyanisole by isolated rat hepatocytes. Drug Metab Dispos. 2002;30:1063–9.CrossRefPubMed
6.
go back to reference Riley PA, Cooksey CJ, Johnson CI, Land EJ, Latter AM, Ramsden CA. Melanogenesis-targeted anti-melanoma pro-drug development: effect of side-chain variations on the cytotoxicity of tyrosinase-generated ortho-quinones in a model screening system. Eur J Cancer. 1997;33:135–43.CrossRefPubMed Riley PA, Cooksey CJ, Johnson CI, Land EJ, Latter AM, Ramsden CA. Melanogenesis-targeted anti-melanoma pro-drug development: effect of side-chain variations on the cytotoxicity of tyrosinase-generated ortho-quinones in a model screening system. Eur J Cancer. 1997;33:135–43.CrossRefPubMed
7.
go back to reference Vad NM, Yount G, Moore D, Weidanz J, Moridani MY. Biochemical mechanism of acetaminophen (APAP) induced toxicity in melanoma cell lines. J Pharm Sci. 2009;98:1409–25.CrossRefPubMedPubMedCentral Vad NM, Yount G, Moore D, Weidanz J, Moridani MY. Biochemical mechanism of acetaminophen (APAP) induced toxicity in melanoma cell lines. J Pharm Sci. 2009;98:1409–25.CrossRefPubMedPubMedCentral
8.
go back to reference Vad NM, Yount G, Moridani MY. Biochemical mechanism of acetylsalicylic acid (aspirin) selective toxicity toward melanoma cell lines. Melanoma Res. 2008;18:386–99.CrossRefPubMed Vad NM, Yount G, Moridani MY. Biochemical mechanism of acetylsalicylic acid (aspirin) selective toxicity toward melanoma cell lines. Melanoma Res. 2008;18:386–99.CrossRefPubMed
10.
go back to reference Harris RE, Beebe-Donk J, Doss H, Burr Doss D. Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (review). Oncology Rep. 2005;13:559–83. Harris RE, Beebe-Donk J, Doss H, Burr Doss D. Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (review). Oncology Rep. 2005;13:559–83.
12.
go back to reference Sahasrabuddhe VV, Gunja MZ, Graubard BI, Trabert B, Schwartz LM, Park Y, et al. Nonsteroidal anti-inflammatory drug use, chronic liver disease, and hepatocellular carcinoma. J Natl Cancer Inst. 2012;104:1808–14.CrossRefPubMedPubMedCentral Sahasrabuddhe VV, Gunja MZ, Graubard BI, Trabert B, Schwartz LM, Park Y, et al. Nonsteroidal anti-inflammatory drug use, chronic liver disease, and hepatocellular carcinoma. J Natl Cancer Inst. 2012;104:1808–14.CrossRefPubMedPubMedCentral
13.
go back to reference Veitonmaki T, Tammela TL, Auvinen A, Murtola TJ. Use of aspirin, but not other non-steroidal anti-inflammatory drugs is associated with decreased prostate cancer risk at the population level. Eur J Cancer. 2013;49:938–45.CrossRefPubMed Veitonmaki T, Tammela TL, Auvinen A, Murtola TJ. Use of aspirin, but not other non-steroidal anti-inflammatory drugs is associated with decreased prostate cancer risk at the population level. Eur J Cancer. 2013;49:938–45.CrossRefPubMed
14.
go back to reference Gamba CA, Swetter SM, Stefanick ML, Kubo J, Desai M, Spaunhurst KM, et al. Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women: the women’s health initiative. Cancer. 2013;119:1562–9.CrossRefPubMed Gamba CA, Swetter SM, Stefanick ML, Kubo J, Desai M, Spaunhurst KM, et al. Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women: the women’s health initiative. Cancer. 2013;119:1562–9.CrossRefPubMed
15.
go back to reference Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nat Rev Clin Oncol. 2012;9:259–67.CrossRefPubMed Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nat Rev Clin Oncol. 2012;9:259–67.CrossRefPubMed
16.
go back to reference Sun Y, Chen J, Rigas B. Chemopreventive agents induce oxidative stress in cancer cells leading to COX-2 overexpression and COX-2-independent cell death. Carcinogenesis. 2009;30:93–9100.CrossRefPubMed Sun Y, Chen J, Rigas B. Chemopreventive agents induce oxidative stress in cancer cells leading to COX-2 overexpression and COX-2-independent cell death. Carcinogenesis. 2009;30:93–9100.CrossRefPubMed
17.
go back to reference Lai MY, Huang JA, Liang ZH, Jiang HX, Tang GD. Mechanisms underlying aspirin-mediated growth inhibition and apoptosis induction of cyclooxygenase-2 negative colon cancer cell line SW480. World J Gastroenterol. 2008;14:4227–33.CrossRefPubMedPubMedCentral Lai MY, Huang JA, Liang ZH, Jiang HX, Tang GD. Mechanisms underlying aspirin-mediated growth inhibition and apoptosis induction of cyclooxygenase-2 negative colon cancer cell line SW480. World J Gastroenterol. 2008;14:4227–33.CrossRefPubMedPubMedCentral
18.
go back to reference Moridani MY, Moore M, Bartsch RA, Yang Y, Heibati-Sadati S. Structural toxicity relationship of 4-alkoxyphenols’ cytotoxicity towards murine B16-F0 melanoma cell line. J Pharm Pharm Sci. 2005;8:348–60.PubMed Moridani MY, Moore M, Bartsch RA, Yang Y, Heibati-Sadati S. Structural toxicity relationship of 4-alkoxyphenols’ cytotoxicity towards murine B16-F0 melanoma cell line. J Pharm Pharm Sci. 2005;8:348–60.PubMed
19.
go back to reference Moridani MY. Biochemical basis of 4-hydroxyanisole induced cell toxicity towards B16-F0 melanoma cells. Cancer Lett. 2006;243:235–45.CrossRefPubMed Moridani MY. Biochemical basis of 4-hydroxyanisole induced cell toxicity towards B16-F0 melanoma cells. Cancer Lett. 2006;243:235–45.CrossRefPubMed
20.
go back to reference Wu X, Zeng H, Zhang X, Zhao Y, Sha H, Ge X, et al. Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells. Am J Pathol. 2004;164:2039–54.CrossRefPubMedPubMedCentral Wu X, Zeng H, Zhang X, Zhao Y, Sha H, Ge X, et al. Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells. Am J Pathol. 2004;164:2039–54.CrossRefPubMedPubMedCentral
21.
go back to reference Moridani MY, Cheon SS, Khan S, O’Brien PJ. Metabolic activation of 3-hydroxyanisole by isolated rat hepatocytes. Chem Biol Interact. 2003;142:317–33.CrossRefPubMed Moridani MY, Cheon SS, Khan S, O’Brien PJ. Metabolic activation of 3-hydroxyanisole by isolated rat hepatocytes. Chem Biol Interact. 2003;142:317–33.CrossRefPubMed
22.
go back to reference Moldeus P, Hogberg J, Orrenius S. Isolation and use of liver cells. Methods Enzymol. 1978;52:60–71.CrossRefPubMed Moldeus P, Hogberg J, Orrenius S. Isolation and use of liver cells. Methods Enzymol. 1978;52:60–71.CrossRefPubMed
23.
go back to reference Shaik IH, Mehvar R. Rapid determination of reduced and oxidized glutathione levels using a new thiol-masking reagent and the enzymatic recycling method: application to the rat liver and bile samples. Anal Bioanal Chem. 2006;385:105–13.CrossRefPubMedPubMedCentral Shaik IH, Mehvar R. Rapid determination of reduced and oxidized glutathione levels using a new thiol-masking reagent and the enzymatic recycling method: application to the rat liver and bile samples. Anal Bioanal Chem. 2006;385:105–13.CrossRefPubMedPubMedCentral
24.
go back to reference Vad NM, Shaik IH, Mehvar R, Moridani MY. Metabolic bioactivation and toxicity of ethyl 4-hydroxybenzoate in human SK-MEL-28 melanoma cells. J Pharm Sci. 2008;97:1934–45.CrossRefPubMed Vad NM, Shaik IH, Mehvar R, Moridani MY. Metabolic bioactivation and toxicity of ethyl 4-hydroxybenzoate in human SK-MEL-28 melanoma cells. J Pharm Sci. 2008;97:1934–45.CrossRefPubMed
25.
go back to reference Siraki AG, Chan TS, O’Brien PJ. Application of quantitative structure-toxicity relationships for the comparison of the cytotoxicity of 14 p-benzoquinone congeners in primary cultured rat hepatocytes versus PC12 cells. Toxicol Sci. 2004;81:148–59.CrossRefPubMed Siraki AG, Chan TS, O’Brien PJ. Application of quantitative structure-toxicity relationships for the comparison of the cytotoxicity of 14 p-benzoquinone congeners in primary cultured rat hepatocytes versus PC12 cells. Toxicol Sci. 2004;81:148–59.CrossRefPubMed
26.
go back to reference Qiao J, Wang H, Kottke T, White C, Twigger K, Diaz RM, et al. Cyclophosphamide facilitates antitumor efficacy against subcutaneous tumors following intravenous delivery of reovirus. Clin Cancer Res. 2008;14:259–69.CrossRefPubMedPubMedCentral Qiao J, Wang H, Kottke T, White C, Twigger K, Diaz RM, et al. Cyclophosphamide facilitates antitumor efficacy against subcutaneous tumors following intravenous delivery of reovirus. Clin Cancer Res. 2008;14:259–69.CrossRefPubMedPubMedCentral
27.
go back to reference Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 1968;25:192–205.CrossRefPubMed Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 1968;25:192–205.CrossRefPubMed
29.
go back to reference Kaur G, Tirkey N, Bharrhan S, Chanana V, Rishi P, Chopra K. Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin-induced experimental hepatoxicity in rodents. Clin Exp Immunol. 2006;145:313–21.CrossRefPubMedPubMedCentral Kaur G, Tirkey N, Bharrhan S, Chanana V, Rishi P, Chopra K. Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin-induced experimental hepatoxicity in rodents. Clin Exp Immunol. 2006;145:313–21.CrossRefPubMedPubMedCentral
30.
go back to reference Carson III WE WM: Animal models of melanoma. In: Tumor models in cancer research. Humana Press Inc., 2002. Carson III WE WM: Animal models of melanoma. In: Tumor models in cancer research. Humana Press Inc., 2002.
31.
go back to reference Kawai S, Yoshinari M, Matsumoto J, Kirinoki M, Aikawa M, Minami M, et al. Plasmodium coatneyi-infected erythrocytes bind to C32 amelanotic melanoma cells under static and flow conditions. J Vet Med Sci. 2003;65:375–80.CrossRefPubMed Kawai S, Yoshinari M, Matsumoto J, Kirinoki M, Aikawa M, Minami M, et al. Plasmodium coatneyi-infected erythrocytes bind to C32 amelanotic melanoma cells under static and flow conditions. J Vet Med Sci. 2003;65:375–80.CrossRefPubMed
32.
go back to reference Kelloff GJ, Boone CW, Crowell JA, Steele VE, Lubet R, Sigman CC. Chemopreventive drug development: perspectives and progress. Cancer Epidemiol Biomarkers Prev. 1994;3:85–98.PubMed Kelloff GJ, Boone CW, Crowell JA, Steele VE, Lubet R, Sigman CC. Chemopreventive drug development: perspectives and progress. Cancer Epidemiol Biomarkers Prev. 1994;3:85–98.PubMed
33.
go back to reference Roberts I: Lj, & jd. Morrow. Analgesic-antipyretic and antiinflammatory agents and drugs employed in the treatment of gout. Goodman & Gilman’s the pharmacological basis of therapeutics, 10th edition, International Edition, Editado por Hardman JG, Limbird LE y Gilman AG, McGraw-Hill:New York; 2001. 703–705. Roberts I: Lj, & jd. Morrow. Analgesic-antipyretic and antiinflammatory agents and drugs employed in the treatment of gout. Goodman & Gilman’s the pharmacological basis of therapeutics, 10th edition, International Edition, Editado por Hardman JG, Limbird LE y Gilman AG, McGraw-Hill:New York; 2001. 703–705.
36.
go back to reference Dovizio M, Bruno A, Tacconelli S, Patrignani P. Mode of action of aspirin as a chemopreventive agent. Recent Results Cancer Res Fortschritte der Krebsforschung Progres dans les recherches sur le cancer. 2013;191:39–65.PubMed Dovizio M, Bruno A, Tacconelli S, Patrignani P. Mode of action of aspirin as a chemopreventive agent. Recent Results Cancer Res Fortschritte der Krebsforschung Progres dans les recherches sur le cancer. 2013;191:39–65.PubMed
37.
go back to reference Tiboni GM, Iammarrone E, Piccirillo G, Liberati M, Bellati U. Aspirin pretreatment potentiates hyperthermia-induced teratogenesis in the mouse. Am J Obstet Gynecol. 1998;178:270–9.CrossRefPubMed Tiboni GM, Iammarrone E, Piccirillo G, Liberati M, Bellati U. Aspirin pretreatment potentiates hyperthermia-induced teratogenesis in the mouse. Am J Obstet Gynecol. 1998;178:270–9.CrossRefPubMed
38.
go back to reference Reddy BS, Rao CV, Rivenson A, Kelloff G. Inhibitory effect of aspirin on azoxymethane-induced colon carcinogenesis in F344 rats. Carcinogenesis. 1993;14:1493–7.CrossRefPubMed Reddy BS, Rao CV, Rivenson A, Kelloff G. Inhibitory effect of aspirin on azoxymethane-induced colon carcinogenesis in F344 rats. Carcinogenesis. 1993;14:1493–7.CrossRefPubMed
39.
go back to reference Duperron C, Castonguay A. Chemopreventive efficacies of aspirin and sulindac against lung tumorigenesis in A/J mice. Carcinogenesis. 1997;18:1001–6.CrossRefPubMed Duperron C, Castonguay A. Chemopreventive efficacies of aspirin and sulindac against lung tumorigenesis in A/J mice. Carcinogenesis. 1997;18:1001–6.CrossRefPubMed
Metadata
Title
Efficacy of acetylsalicylic acid (aspirin) in skin B16-F0 melanoma tumor-bearing C57BL/6 mice
Authors
Nikhil M. Vad
Shashi K. Kudugunti
Hezhen Wang
G. Jayarama Bhat
Majid Y. Moridani
Publication date
01-05-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-1654-1

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