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Mar. Drugs 2019, 17(1), 63; https://doi.org/10.3390/md17010063

Tetracenomycin X Exerts Antitumour Activity in Lung Cancer Cells through the Downregulation of Cyclin D1

Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, 1# Tiantan Xili, Chong Wen District, Beijing 100050, China
*
Author to whom correspondence should be addressed.
These authors contributed to equally to this works.
Received: 2 December 2018 / Revised: 10 January 2019 / Accepted: 15 January 2019 / Published: 18 January 2019
(This article belongs to the Collection Marine Compounds and Cancer)
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Abstract

Tetracenomycin X (Tcm X) has been reported to have antitumour activity in various cancers, but there have not been any studies on its activity with respect to lung cancer to date. Therefore, this study aims to investigate the anti-lung cancer activity of Tcm X. In this study, we found that tetracenomycin X showed antitumour activity in vivo and selectively inhibited the proliferation of lung cancer cells without influencing lung fibroblasts. In addition, apoptosis and autophagy did not contribute to the antitumour activity. Tetracenomycin X exerts antitumour activity through cell cycle arrest induced by the downregulation of cyclin D1. To explore the specific mechanism, we found that tetracenomycin X directly induced cyclin D1 proteasomal degradation and indirectly downregulated cyclin D1 via the activation of p38 and c-JUN proteins. All these findings were explored for the first time, which indicated that tetracenomycin X may be a powerful antimitotic class of anticancer drug candidates for the treatment of lung cancer in the future. View Full-Text
Keywords: tetracenomycin X; cell cycle arrest; cyclin D1; proteasomal degradation; p38; c-JUN tetracenomycin X; cell cycle arrest; cyclin D1; proteasomal degradation; p38; c-JUN
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Qiao, X.; Gan, M.; Wang, C.; Liu, B.; Shang, Y.; Li, Y.; Chen, S. Tetracenomycin X Exerts Antitumour Activity in Lung Cancer Cells through the Downregulation of Cyclin D1. Mar. Drugs 2019, 17, 63.

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