Marine Sponge Cribrochalina vasculum Compounds Activate Intrinsic Apoptotic Signaling and Inhibit Growth Factor Signaling Cascades in Non-Small Cell Lung Carcinoma
2014 (English)In: Molecular Cancer Therapeutics, ISSN 1535-7163, E-ISSN 1538-8514, Vol. 13, no 12, 2941-2954 p.Article in journal (Refereed) Published
Marine-derived compounds have been explored and considered as possible antitumor agents. In this study, we analyzed extracts of the sponge Cribrochalina vasculum for their ability to inhibit tumor cell proliferation. Screening identified two acetylenic compounds of similar structure that showed strong tumor-specific toxicity in non-small cell lung carcinoma (NSCLC) cells and small-cell lung carcinoma cells, and less prominent toxicity in ovarian carcinoma, while having no effect on normal cells. These acetylenic compounds were found to cause a time-dependent increase in activation of apoptotic signaling involving cleavage of caspase-9, caspase-3, and PARP, as well as apoptotic cell morphology in NSCLC cells, but not in normal fibroblasts. Further analysis demonstrated that these compounds caused conformational change in Bak and Bax, and resulted in loss of mitochondrial potential and cytochrome c release in NSCLC cells. Moreover, a decreased phosphorylation of the growth factor signaling kinases Akt, mTOR, and ERK was evident and an increased phosphorylation of JNK was observed. Thus, these acetylenic compounds hold potential as novel therapeutic agents that should be further explored for NSCLC and other tumor malignancies.
Place, publisher, year, edition, pages
2014. Vol. 13, no 12, 2941-2954 p.
Cancer and Oncology
IdentifiersURN: urn:nbn:se:su:diva-113129DOI: 10.1158/1535-7163.MCT-14-0329ISI: 000346132900016OAI: oai:DiVA.org:su-113129DiVA: diva2:790751
FunderSwedish Cancer SocietySwedish Research CouncilSwedish National Board of Health and WelfareThe Karolinska Institutet's Research Foundation
AuthorCount:9;[EGENFarnegardh, Katarina]Stockholm Univ, Dept Organ Chem, Drug Discovery & Dev Platform, Sci Life Lab, Stockholm, Sweden2015-02-252015-01-232015-09-28Bibliographically approved