Aaptamines from the marine sponge Aaptos sp. display anticancer activities in human cancer cell lines and modulate AP-1-, NF-κB-, and p53-dependent transcriptional activity in mouse JB6 Cl41 cells

TY - JOUR

T1 - Aaptamines from the marine sponge Aaptos sp. display anticancer activities in human cancer cell lines and modulate AP-1-, NF-κB-, and p53-dependent transcriptional activity in mouse JB6 Cl41 cells

AU - Dyshlovoy, Sergey A

AU - Fedorov, Sergey N

AU - Shubina, Larisa K

AU - Kuzmich, Alexandra S

AU - Bokemeyer, Carsten

AU - Amsberg, Gunhild

AU - Honecker, Friedemann

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Aaptamine (8,9-dimethoxy-1H-benzo[de][1,6]naphthyridine) is a marine natural compound possessing antioxidative, antimicrobial, antifungal, and antiretroviral activity. Earlier, we have found that aaptamine and its derivatives demonstrate equal anticancer effects against the human germ cell cancer cell lines NT2 and NT2-R and cause some changes in the proteome of these cells. In order to explore further the mechanism of action of aaptamine and its derivatives, we studied the effects of aaptamine (1), demethyl(oxy)aaptamine (2), and isoaaptamine (3) on human cancer cell lines and on AP-1-, NF-κB-, and p53-dependent transcriptional activity in murine JB6 Cl41 cells. We showed that compounds 1-3 demonstrate anticancer activity in THP-1, HeLa, SNU-C4, SK-MEL-28, and MDA-MB-231 human cancer cell lines. Additionally, all compounds were found to prevent EGF-induced neoplastic transformation of murine JB6 Cl41 cells. Nuclear factors AP-1, NF-κB, and p53 are involved in the cellular response to high and nontoxic concentrations of aaptamine alkaloids 1-3. Furthermore, inhibition of EGF-induced JB6 cell transformation, which is exerted by the compounds 1-3 at low nontoxic concentrations of 0.7-2.1 μM, cannot be explained by activation of AP-1 and NF-κB.

AB - Aaptamine (8,9-dimethoxy-1H-benzo[de][1,6]naphthyridine) is a marine natural compound possessing antioxidative, antimicrobial, antifungal, and antiretroviral activity. Earlier, we have found that aaptamine and its derivatives demonstrate equal anticancer effects against the human germ cell cancer cell lines NT2 and NT2-R and cause some changes in the proteome of these cells. In order to explore further the mechanism of action of aaptamine and its derivatives, we studied the effects of aaptamine (1), demethyl(oxy)aaptamine (2), and isoaaptamine (3) on human cancer cell lines and on AP-1-, NF-κB-, and p53-dependent transcriptional activity in murine JB6 Cl41 cells. We showed that compounds 1-3 demonstrate anticancer activity in THP-1, HeLa, SNU-C4, SK-MEL-28, and MDA-MB-231 human cancer cell lines. Additionally, all compounds were found to prevent EGF-induced neoplastic transformation of murine JB6 Cl41 cells. Nuclear factors AP-1, NF-κB, and p53 are involved in the cellular response to high and nontoxic concentrations of aaptamine alkaloids 1-3. Furthermore, inhibition of EGF-induced JB6 cell transformation, which is exerted by the compounds 1-3 at low nontoxic concentrations of 0.7-2.1 μM, cannot be explained by activation of AP-1 and NF-κB.

KW - Animals

KW - Antineoplastic Agents

KW - Apoptosis

KW - Cell Line

KW - Cell Line, Tumor

KW - Humans

KW - Mice

KW - NF-kappa B

KW - Naphthyridines

KW - Porifera

KW - Transcription Factor AP-1

KW - Transcription, Genetic

KW - Tumor Suppressor Protein p53

U2 - 10.1155/2014/469309

DO - 10.1155/2014/469309

M3 - SCORING: Journal article

C2 - 25215281

VL - 2014

SP - 469309

JO - BIOMED RES INT

JF - BIOMED RES INT

SN - 2314-6133

ER -