Anticancer effects of Ac‑Phe‑Lys‑PABC‑doxorubicin via mitochondria‑centered apoptosis involving reactive oxidative stress and the ERK1/2 signaling pathway in MGC‑803 cells

  • Authors:
    • Yan‑Jun Zhong
    • Shao‑Ping Liu
    • Raymond A. Firestone
    • Ya‑Ping Hong
    • Yan Li
  • View Affiliations

  • Published online on: July 19, 2013     https://doi.org/10.3892/or.2013.2629
  • Pages: 1681-1686
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Abstract

Ac‑Phe‑Lys‑PABC‑DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. The present study aimed to elucidate the molecular mechanisms of action of PDOX using MGC‑803 gastric cancer cells as a model. The cells were treated with both PDOX and DOX, and cytotoxicities, cell cycle analysis, reactive oxygen species (ROS) generation, mitochondrial damage and ERK1/2 signaling pathway alterations were studied. Abundant cathepsin B expression was observed in the MGC‑803 cells, and treatment with PDOX and DOX triggered dose‑dependent cytotoxicity and resulted in a significant reduction in cell viability. IC50 of PDOX and DOX was 14.9 and 4.9 µM, respectively. Both PDOX and DOX significantly decreased p‑ERK1/2, increased ROS generation, reduced mitochondrial membrane potential, caused mitochondrial swelling and arrested the cell cycle at the G2/S phase, and these effects were more pronounced for PDOX than for DOX. PDOX and DOX have different mechanisms of action, particularly the mitochondria‑centered intrinsic apoptosis involving reactive oxidative stress and the ERK1/2 signaling pathway.
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October 2013
Volume 30 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhong YJ, Liu SP, Firestone RA, Hong YP and Li Y: Anticancer effects of Ac‑Phe‑Lys‑PABC‑doxorubicin via mitochondria‑centered apoptosis involving reactive oxidative stress and the ERK1/2 signaling pathway in MGC‑803 cells. Oncol Rep 30: 1681-1686, 2013.
APA
Zhong, Y., Liu, S., Firestone, R.A., Hong, Y., & Li, Y. (2013). Anticancer effects of Ac‑Phe‑Lys‑PABC‑doxorubicin via mitochondria‑centered apoptosis involving reactive oxidative stress and the ERK1/2 signaling pathway in MGC‑803 cells. Oncology Reports, 30, 1681-1686. https://doi.org/10.3892/or.2013.2629
MLA
Zhong, Y., Liu, S., Firestone, R. A., Hong, Y., Li, Y."Anticancer effects of Ac‑Phe‑Lys‑PABC‑doxorubicin via mitochondria‑centered apoptosis involving reactive oxidative stress and the ERK1/2 signaling pathway in MGC‑803 cells". Oncology Reports 30.4 (2013): 1681-1686.
Chicago
Zhong, Y., Liu, S., Firestone, R. A., Hong, Y., Li, Y."Anticancer effects of Ac‑Phe‑Lys‑PABC‑doxorubicin via mitochondria‑centered apoptosis involving reactive oxidative stress and the ERK1/2 signaling pathway in MGC‑803 cells". Oncology Reports 30, no. 4 (2013): 1681-1686. https://doi.org/10.3892/or.2013.2629