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Anti-cancer effects of novel doxorubicin prodrug PDOX in MCF-7 breast cancer cells

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Summary

Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. This study was aimed at elucidating the effectiveness and toxicities of DOX and PDOX in patient-derived MCF-7 breast cancer cells in vitro. The MCF-7 cells were exposed to both PDOX and DOX, and cytotoxicities, cell cycle and P53/P21 signaling alterations were studied. Abundant cathepsin B was found in the MCF-7 cells, and treatment with PDOX and DOX triggered dose- and time-dependent cytotoxicity and resulted in a significant reduction in cell viability. The IC50 of PDOX and DOX was 3.91 and 0.94 μmol/L, respectively. Both PDOX and DOX caused an up-regulation of the P53/P21-related signal pathway, and PDOX significantly increased expression of P53 and caspase 3, and arrested the cell cycle at the G1/G2 phase. As compared with DOX, PDOX reduced toxicities, and it may have different action mechanisms on breast cancer cells.

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Authors and Affiliations

  1. Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China

    Jue Zhang  (张 珏), Liang He  (何 良), Xia-fei Geng  (耿霞飞) & Yan Li  (李 雁)

  2. Nanjing Meihua Pharmaceuticals, Ltd, Nanjing, 210009, China

    Raymond A. Firestone & Ya-ping Hong  (洪亚平)

  3. Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, China

    Yan Li  (李 雁)

Authors
  1. Jue Zhang  (张 珏)
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  2. Liang He  (何 良)
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  3. Xia-fei Geng  (耿霞飞)
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  4. Raymond A. Firestone
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  5. Ya-ping Hong  (洪亚平)
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  6. Yan Li  (李 雁)
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Corresponding author

Correspondence to Yan Li  (李 雁).

Additional information

These authors contributed equally to this work.

This project was supported by the grants from the Science Fund for Doctorate Mentors by Ministry of Education of China (No. 20120141110042), New Strategies to Treat Peritoneal Carcinomatosis from Hubei Sciences and Technology Bureau, China (No. 2008BCC011, and No. 2060402-542), and the Fundamental Research Fund for the Central Universities of China (No. 2012303020208).

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Zhang, J., He, L., Geng, Xf. et al. Anti-cancer effects of novel doxorubicin prodrug PDOX in MCF-7 breast cancer cells. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 521–528 (2014). https://doi.org/10.1007/s11596-014-1309-x

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  • DOI: https://doi.org/10.1007/s11596-014-1309-x

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