Open Access

Mitomycin C and decarbamoyl mitomycin C induce p53-independent p21WAF1/CIP1 activation

  • Authors:
    • Shu-Yuan Cheng
    • Jiwon Seo
    • Bik Tzu Huang
    • Tanya Napolitano
    • Elise Champeil
  • View Affiliations

  • Published online on: September 23, 2016     https://doi.org/10.3892/ijo.2016.3703
  • Pages: 1815-1824
  • Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mitomycin C (MC), a commonly used anticancer drug, induces DNA damage via DNA alkylation. Decarbamoyl mitomycin C (DMC), another mitomycin lacking the carbamate at C10, generates similar lesions as MC. Interstrand cross-links (ICLs) are believed to be the lesions primarily responsible for the cytotoxicity of MC and DMC. The major ICL generated by MC (α-ICL) has a trans stereochemistry at the guanine-drug linkage whereas the major ICL from DMC (β-ICL) has the opposite, cis, stereochemistry. In addition, DMC can provoke strong p53-independent cell death. Our hypothesis is that the stereochemistry of the major unique β-ICL generated by DMC is responsible for this p53-independent cell death signaling. p53 gene is inactively mutated in more than half of human cancers. p21WAF1/CIP1 known as a major effector of p53 is involved in p53-dependent and -independent control of cell proliferation and death. This study revealed the role of p21WAF1/CIP1 on MC and DMC triggered cell damage. MCF-7 (p53-proficient) and K562 (p53-deficient) cells were used. Cell cycle distributions were shifted to the G1/S phase in MCF-7 treated with MC and DMC, but were shifted to the S phase in K562. p21WAF1/CIP1 activation was observed in both cells treated with MC and DMC, and DMC triggered more significant activation. Knocking down p53 in MCF-7 did not attenuate MC and DMC induced p21WAF1/CIP1 activation. The α-ICL itself was enough to cause p21WAF1/CIP1 activation.
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November-2016
Volume 49 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Cheng S, Seo J, Huang BT, Napolitano T and Champeil E: Mitomycin C and decarbamoyl mitomycin C induce p53-independent p21WAF1/CIP1 activation. Int J Oncol 49: 1815-1824, 2016
APA
Cheng, S., Seo, J., Huang, B.T., Napolitano, T., & Champeil, E. (2016). Mitomycin C and decarbamoyl mitomycin C induce p53-independent p21WAF1/CIP1 activation. International Journal of Oncology, 49, 1815-1824. https://doi.org/10.3892/ijo.2016.3703
MLA
Cheng, S., Seo, J., Huang, B. T., Napolitano, T., Champeil, E."Mitomycin C and decarbamoyl mitomycin C induce p53-independent p21WAF1/CIP1 activation". International Journal of Oncology 49.5 (2016): 1815-1824.
Chicago
Cheng, S., Seo, J., Huang, B. T., Napolitano, T., Champeil, E."Mitomycin C and decarbamoyl mitomycin C induce p53-independent p21WAF1/CIP1 activation". International Journal of Oncology 49, no. 5 (2016): 1815-1824. https://doi.org/10.3892/ijo.2016.3703