| In vitro: |
| J Proteomics. 2014 Jan 16;96:223-39. | | Activity of aaptamine and two derivatives, demethyloxyaaptamine and isoaaptamine, in cisplatin-resistant germ cell cancer.[Pubmed: 24269226 ] | We analyzed the effects of all three marine alkaloids Aaptamine, demethyloxyAaptamine and isoAaptamine in NT2-R, a cisplatin-resistant subline of the human embryonal carcinoma cell line NT2.
METHODS AND RESULTS:
All Aaptamines were found to be equally effective in both cell lines, excluding cross-resistance between Aaptamines and cisplatin in vitro. At the inhibitory concentration (IC50), Aaptamine exerted an antiproliferative effect, whereas demethyloxyAaptamine and isoAaptamine were strong inducers of apoptosis. We analyzed the changes in the proteome of NT2-R cells treated with these compounds. 16-22 proteins were found to be significantly altered, of which several were validated by Western blotting and two-dimensional Western blotting analysis. Changes in the proteome pattern frequently resulted from post-transcriptional protein modifications, i.e. phosphorylation or hypusination in the case of eIF5A. Although the lists of altered proteins were heterogeneous and compound-specific, gene ontology analyses identified rather similar profiles regarding the affected molecular functions. Ingenuity pathway analysis by IPA put the following factors in a central position of the hypothetical networks: myc and p53 for Aaptamine; tumor necrosis factor (TNF) for demethyloxyAaptamine; and all three, myc, p53, and TNF for isoAaptamine.
CONCLUSIONS:
Our results represent an important step towards a better understanding of the molecular basis underlying the observed bioactivity of these promising marine compounds. | | J Pharm Pharmacol. 1984 Nov;36(11):785-6. | | Alpha-adrenoceptor blocking action of aaptamine, a novel marine natural product, in vascular smooth muscle.[Pubmed: 6150989] |
METHODS AND RESULTS:
In the rabbit isolated aorta and renal artery, aaptamine (3 X 10(-5)M), a novel heteroaromatic substance isolated from a sea sponge Aaptos aaptos produced a parallel, rightward shift of the dose-response curve for noradrenaline, whereas that for histamine or KCl was not affected. But, the derivatives of aaptamine, demethylaaptamine, demethyloxyaaptamine, dihydroaaptamine and dihydrodemethylaaptamine at concentrations of 10(-5) to 10(-4)M had no effect on the dose-response curve for noradrenaline.
CONCLUSIONS:
These results suggest that aaptamine is a competitive antagonist of alpha-adrenoceptors in vascular smooth muscles. | | J Asian Nat Prod Res. 2014 Dec;16(12):1139-47. | | Anti-photoaging effect of aaptamine in UVB-irradiated human dermal fibroblasts and epidermal keratinocytes.[Pubmed: 25465718 ] | Chronic exposure to ultraviolet (UV) irradiation causes sunburn, inflammatory responses, skin cancer, and photoaging. Photoaging, in particular, generates reactive oxygen species (ROS) that stimulate mitogen-activated protein kinase (MAPK) signaling and transcription factors. UV irradiation also activates matrix metalloproteinases (MMPs) expression and inactivates collagen synthesis. Aaptamine, a marine alkaloid isolated from the marine sponge, has been reported to have antitumor, antimicrobial, antiviral, and antioxidant activities. However, the photo-protective effects of Aaptamine have not been elucidated.
METHODS AND RESULTS:
In this study, our data demonstrated that Aaptamine deactivated UVB-induced MAPK and activator protein-1 signaling by suppressing ROS, resulting in attenuating the expression of MMPs in UVB-irradiated human dermal fibroblasts. Aaptamine also decreased proinflammatory cytokines such as cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β, and nuclear factor-kappa B subunits in UVB-irradiated human keratinocytes.
CONCLUSIONS:
In conclusion, we suggest that Aaptamine represents a novel and effective strategy for treatment and prevention of photoaging. |
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