Tanshinone IIA regulates colorectal cancer apoptosis via attenuation of Parkin‑mediated mitophagy by suppressing AMPK/Skp2 pathways

  • Authors:
    • Lili He
    • Kebo Gu
  • View Affiliations

  • Published online on: May 29, 2018     https://doi.org/10.3892/mmr.2018.9087
  • Pages: 1692-1703
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Abstract

Mitophagy is important for cancer development. Notably, the role of Parkin‑mediated mitophagy in colorectal cancer (CRC) mortality has not been fully determined. Therefore, the present study aimed to investigate the effect of Parkin‑mediated mitophagy on CRC apoptosis. In addition, the present study investigated the therapeutic effects of Tanshinone IIA (Tan IIA) on the regulation of CRC cell death via mitophagy. Cellular apoptosis was measured following Tan IIA treatment. In addition, mitophagy activity was evaluated by immunofluorescence and western blotting. The results of the present study revealed that Tan IIA may enhance CRC cell death. In addition, the results demonstrated that Tan IIA enhanced mitochondrial apoptosis, as demonstrated by reduced mitochondrial membrane potential, elevated mitochondrial permeability transition pore opening, and increased oxidative stress, mitochondrial energy disorder and proapoptotic factor expression. Furthermore, the results of the present study demonstrated that Tan IIA induced mitochondrial apoptosis via inhibition of mitophagy. In addition, it was revealed that mitophagy could suppress mitochondrial apoptosis. Functional assays revealed that Tan IIA suppressed the adenosine monophosphate‑activated protein kinase (AMPK) pathway, resulting in the inactivation of S‑phase kinase associated protein 2 (Skp2). Furthermore, reduced levels of Skp2 failed to activate Parkin, thus resulting in inhibition of mitophagy. Conversely, reactivation of AMPK and overexpression of Skp2 rescued mitophagy activity and thus attenuated the Tan IIA‑induced apoptosis of CRC cells. In conclusion, the results of the present study demonstrated the beneficial role of mitophagy in CRC cell survival and suggested that Tan IIA may be an effective therapeutic agent, which suppresses mitophagy activity and enhances CRC apoptosis.
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August-2018
Volume 18 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
He L and He L: Tanshinone IIA regulates colorectal cancer apoptosis via attenuation of Parkin‑mediated mitophagy by suppressing AMPK/Skp2 pathways. Mol Med Rep 18: 1692-1703, 2018
APA
He, L., & He, L. (2018). Tanshinone IIA regulates colorectal cancer apoptosis via attenuation of Parkin‑mediated mitophagy by suppressing AMPK/Skp2 pathways. Molecular Medicine Reports, 18, 1692-1703. https://doi.org/10.3892/mmr.2018.9087
MLA
He, L., Gu, K."Tanshinone IIA regulates colorectal cancer apoptosis via attenuation of Parkin‑mediated mitophagy by suppressing AMPK/Skp2 pathways". Molecular Medicine Reports 18.2 (2018): 1692-1703.
Chicago
He, L., Gu, K."Tanshinone IIA regulates colorectal cancer apoptosis via attenuation of Parkin‑mediated mitophagy by suppressing AMPK/Skp2 pathways". Molecular Medicine Reports 18, no. 2 (2018): 1692-1703. https://doi.org/10.3892/mmr.2018.9087