Open Access

Tan IIA inhibits H1299 cell viability through the MDM4‑IAP3 signaling pathway

  • Authors:
    • Yukun Zu
    • Jianning Wang
    • Wei Ping
    • Wei Sun
  • View Affiliations

  • Published online on: November 24, 2017     https://doi.org/10.3892/mmr.2017.8152
  • Pages: 2384-2392
  • Copyright: © Zu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tanshinone IIA (Tan IIA), as a bioactive compound extracted from the dried roots of Salvia miltiorrhiza (also known as Danshen), is known to inhibit cancer cell proliferation and induce apoptosis. However, the mechanisms underlying the function of Tan IIA in cancer cell apoptosis remain to be elucidated The aim of the present study was to identify the molecular mechanisms underlying the anti‑cancer effects of Tan IIA in p53‑deficient H1299 cells. Tan IIA was demonstrated to suppress murine double minute 4 (MDM4) expression in a time‑ and dose‑dependent manner through the inhibition of MDM4 mRNA synthesis. Tan IIA‑induced downregulation of MDM4 resulted in an increase of P73α and a decrease of inhibitor of apoptosis 3 (IAP3). However, P73α was not activated as two P73α target genes, BCL2 binding component 3 and phorbol‑12‑myristate‑13‑acetate‑induced protein 1, were not significantly induced. Tan IIA‑induced inhibition of IAP3 expression may be involved in Tan IIA‑induced apoptosis and inhibition of H1299 cell viability. Notably, a combination of Tan IIA and doxorubicin (DOX) exposure resulted in further MDM4 overexpression in H1299 cells, indicating that Tan IIA sensitized p53‑deficient and MDM4‑overexpressing H1299 cells to DOX‑induced apoptosis.
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February-2018
Volume 17 Issue 2

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

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Spandidos Publications style
Zu Y, Wang J, Ping W and Sun W: Tan IIA inhibits H1299 cell viability through the MDM4‑IAP3 signaling pathway. Mol Med Rep 17: 2384-2392, 2018
APA
Zu, Y., Wang, J., Ping, W., & Sun, W. (2018). Tan IIA inhibits H1299 cell viability through the MDM4‑IAP3 signaling pathway. Molecular Medicine Reports, 17, 2384-2392. https://doi.org/10.3892/mmr.2017.8152
MLA
Zu, Y., Wang, J., Ping, W., Sun, W."Tan IIA inhibits H1299 cell viability through the MDM4‑IAP3 signaling pathway". Molecular Medicine Reports 17.2 (2018): 2384-2392.
Chicago
Zu, Y., Wang, J., Ping, W., Sun, W."Tan IIA inhibits H1299 cell viability through the MDM4‑IAP3 signaling pathway". Molecular Medicine Reports 17, no. 2 (2018): 2384-2392. https://doi.org/10.3892/mmr.2017.8152