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Mar. Drugs 2015, 13(1), 543-557; doi:10.3390/md13010543

Activation of p53 with Ilimaquinone and Ethylsmenoquinone, Marine Sponge Metabolites, Induces Apoptosis and Autophagy in Colon Cancer Cells

1
Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Korea
2
College of Pharmacy, Chungnam national University, 305-764 Daejeon, Korea
3
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
4
Department of Life Science, Sogang University, Seoul 121-742, Korea
5
Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea
6
BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Keith B. Glaser
Received: 16 November 2014 / Accepted: 7 January 2015 / Published: 16 January 2015
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Abstract

The tumor suppressor, p53, plays an essential role in the cellular response to stress through regulating the expression of genes involved in cell cycle arrest, apoptosis and autophagy. Here, we used a cell-based reporter system for the detection of p53 response transcription to identify the marine sponge metabolites, ilimaquinone and ethylsmenoquinone, as activators of the p53 pathway. We demonstrated that ilimaquinone and ethylsmenoquinone efficiently stabilize the p53 protein through promotion of p53 phosphorylation at Ser15 in both HCT116 and RKO colon cancer cells. Moreover, both compounds upregulate the expression of p21WAF1/CIP1, a p53-dependent gene, and suppress proliferation of colon cancer cells. In addition, ilimaquinone and ethylsmenoquinone induced G2/M cell cycle arrest and increased caspase-3 cleavage and the population of cells that positively stained with Annexin V-FITC, both of which are typical biochemical markers of apoptosis. Furthermore, autophagy was elicited by both compounds, as indicated by microtubule-associated protein 1 light chain 3 (LC3) puncta formations and LC3-II turnover in HCT116 cells. Our findings suggest that ilimaquinone and ethylsmenoquinone exert their anti-cancer activity by activation of the p53 pathway and may have significant potential as chemo-preventive and therapeutic agents for human colon cancer. View Full-Text
Keywords: ilimaquinone; ethylsmenoquinone; p53; colon cancer; apoptosis; autophagy ilimaquinone; ethylsmenoquinone; p53; colon cancer; apoptosis; autophagy
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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MDPI and ACS Style

Lee, H.-Y.; Chung, K.J.; Hwang, I.H.; Gwak, J.; Park, S.; Ju, B.G.; Yun, E.; Kim, D.-E.; Chung, Y.-H.; Na, M.; Song, G.-Y.; Oh, S. Activation of p53 with Ilimaquinone and Ethylsmenoquinone, Marine Sponge Metabolites, Induces Apoptosis and Autophagy in Colon Cancer Cells. Mar. Drugs 2015, 13, 543-557.

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