Abstract 4235: Anti-proliferative effect of (19 Z )-halichondramide from the sponge Chondrosia corticata via G2/M cell cycle arrest and suppression of mTOR signaling in human lung cancer cells

Abstract 4235: Anti-proliferative effect of (19 Z )-halichondramide from the sponge Chondrosia corticata via G2/M cell cycle arrest and suppression of mTOR signaling in human lung cancer cells

Five oxazole-containing macrolides isolated from the marine sponge Chondrosia corticata were evaluated for their anti-proliferative activity in a panel of human solid cancer cell lines. (19Z)-Halichondramide ((19Z)-HCA), a novel trisoxazole-containing macrolide, exhibited the highest potency among t...

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Published in:Cancer research (Chicago, Ill.) Vol. 74; no. 19_Supplement; p. 4235
Main Authors: Bae, Song Y., Song, Jayoung, Shin, Yoonho, Kim, Won Kyung, Oh, Jedo, Choi, Tae Joon, Jeong, Eun Ju, Park, So Hyun, Jang, Eun Jeong, Kang, Ji In, Park, Hyen Joo, Hong, Ji-Young, Kim, Gi Dae, Jeon, Ju-eun, Shin, Jongheon, Lee, Sang Kook
Format: Journal Article
Language:English
Published: 01-10-2014
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Summary:Five oxazole-containing macrolides isolated from the marine sponge Chondrosia corticata were evaluated for their anti-proliferative activity in a panel of human solid cancer cell lines. (19Z)-Halichondramide ((19Z)-HCA), a novel trisoxazole-containing macrolide, exhibited the highest potency among the macrolides, with IC50 values in the submicro-molar ranges. Prompted by the high potency of growth inhibition of cancer cells, we investigated the mechanism of action of the anti-proliferative activity of (19Z)-HCA in human A549 lung cancer cells. (19Z)-HCA induced cell cycle arrest in the G2/M phase, and this event was highly correlated with the expression of checkpoint proteins, including the up-regulation of p53 and GADD45α and the down-regulation of cyclin B1, cyclin A, CDC2, and CDC25C. In addition, the growth inhibition by (19Z)-HCA was associated with the suppression of mTOR and its downstream effector molecules 4EBP1 and p70S6K. The modulation of mTOR signaling by (19Z)-HCA was found to be mediated by the regulation of upstream proteins, including the down-regulation of Akt and p38 MAPK and the up-regulation of AMPK. These data suggest the potential of (19Z)-HCA to serve as a candidate for cancer chemotherapeutic agents derived from marine organisms by virtue of arresting the cell cycle in the G2/M phase and the modulation of mTOR/AMPK signaling pathways. [Acknowledgements: This work was supported by the MarineBio Research Program (NRF-2013045101) of the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MEST).] Citation Format: Song Yi Bae, Jayoung Song, Yoonho Shin, Won Kyung Kim, Jedo Oh, Tae Joon Choi, Eun Ju Jeong, So Hyun Park, Eun Jeong Jang, Ji In Kang, Hyen Joo Park, Ji-Young Hong, Gi Dae Kim, Ju-eun Jeon, Jongheon Shin, Sang Kook Lee. Anti-proliferative effect of (19Z)-halichondramide from the sponge Chondrosia corticata via G2/M cell cycle arrest and suppression of mTOR signaling in human lung cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4235. doi:10.1158/1538-7445.AM2014-4235
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2014-4235