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

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Tumor Biology

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.

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Abbreviations

ASA:

Aspirin, acetylsalicylic acid

DMEM:

Dulbecco’s Modified Eagle Medium

FBS:

Fetal bovine serum

PBS:

Phosphate-buffered saline

TBARS:

Thiobarbituric acid-reactive substances

ALT:

Alanine aminotransferase

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Acknowledgement

This work was supported partly by a grant from NIH (1R15CA122044-01A1) and the TTUHSC School of Pharmacy to M.Y.M and 5RO3CA133061-02 to G.J.B. Support from the Translational Cancer Research Seed Grant to G.J.B, funded as 2010 Research Initiative Center by the State of South Dakota, is also gratefully acknowledged.

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Authors and Affiliations

  1. Department of Pharmaceutical and Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA

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

  2. Department of Pharmaceutical Sciences, South Dakota State University College of Pharmacy, Brookings, SD, 57007, USA

    G. Jayarama Bhat

  3. Department of Pathology, Medical College of Wisconsin, Suite L12, Milwaukee, WI, 53226, USA

    Majid Y. Moridani

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  1. Nikhil M. Vad
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  2. Shashi K. Kudugunti
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  3. Hezhen Wang
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  4. G. Jayarama Bhat
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  5. Majid Y. Moridani
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Correspondence to G. Jayarama Bhat or Majid Y. Moridani.

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Vad, N.M., Kudugunti, S.K., Wang, H. et al. Efficacy of acetylsalicylic acid (aspirin) in skin B16-F0 melanoma tumor-bearing C57BL/6 mice. Tumor Biol. 35, 4967–4976 (2014). https://doi.org/10.1007/s13277-014-1654-1

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