Acacia hydaspica R. Parker is known for its medicinal uses in multiple ailments. In this study, we performed bioassay-guided fractionation of cytotoxic compounds from A. hydaspica and investigated their effects on growth and signaling activity in prostate and breast cancer cell lines. Four active polyphenolic compounds were identified as 7-O-galloyl catechin (GC), catechin (C), methyl gallate (MG), and catechin-3-O-gallate (CG). The four compounds inhibited prostate cancer PC-3 cell growth in a dose-dependent manner, whereas CG and MG inhibited breast cancer MDA-MB-231 cell growth. All tested compounds inhibited cell survival and colony growth in both cell lines, and there was evidence of chromatin condensation, cell shrinkage and apoptotic bodies. Further, acridine orange, ethidium bromide, propidium iodide and DAPI staining demonstrated that cell death occurred partly via apoptosis in both PC-3 and MDA-MB-231 cells. In PC-3 cells treatment repressed the expression of anti-apoptotic molecules Bcl-2, Bcl-xL and survivin, coupled with down-regulation of signaling pathways AKT, NFκB, ERK1/2 and JAK/STAT. In MDA-MB-231 cells, treatment induced reduction of CK2α, Bcl-xL, survivin and xIAP protein expression along with suppression of NFκB, JAK/STAT and PI3K pathways. Our findings suggest that certain polyphenolic compounds derived from A. hydaspica may be promising chemopreventive/therapeutic candidates against cancer.

A case-control study on respiratory cancers was conducted in New Caledonia (South Pacific), where a high incidence of malignant pleural mesothelioma had been observed. The disease pattern suggested an environmental exposure to asbestos. The first results showed that, in some areas, tremolite asbestos derived from local outcroppings was used as whitewash (locally named "pö"). All cases diagnosed between 1993 and 1995 (including 15 pleural mesotheliomas, 228 lung cancers, and 23 laryngeal cancers) and 305 controls were included in the study. Detailed information on past or present use of the whitewash, residential history, smoking, diet, and occupation was collected. The risk of mesothelioma was strongly associated with the use of the whitewash (odds ratio (OR) = 40.9; 95% confidence interval (CI): 5.15, 325). All Melanesian cases had been exposed. Among Melanesian women, exposure to the whitewash was associated with an increased risk of lung cancer (OR = 4.89; 95% CI: 1.13, 21.2), and smokers exposed to po had an approximately ninefold risk (OR = 9.26; 95% CI: 1.72, 49.7) compared with women who never smoked and had never used the whitewash. In contrast, no association was noted between exposure to pö and lung cancer risk among Melanesian men, probably because of lower exposure levels. Among non-Melanesians, the numbers of exposed subjects were too small to assess the effect of exposure to po. There was no indication of elevated risks for the other cancer sites.

Marine invertebrates and a growing number of marine bacteria are the sources of novel, bioactive secondary metabolites. Structurally, many of these compounds appear to be biosynthesized by polyketide synthases (PKS) and/or nonribosomal peptide synthetases (NRPS) that have also been found in terrestrial microbes. This review highlights scientific advances from 1999-2003 in the emerging field of molecular genetics of polyketide and nonribosomal peptide natural products isolated from marine organisms. The implications of this research towards the development of marine secondary metabolites as a sustainable source of new drugs are discussed.

Bifunctional inhibitors were designed and synthesized based on 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)a1 non-nucleoside reverse transcriptase (RT) inhibitors and diketoacid (DKA) integrase (IN) inhibitors. Biochemical studies revealed activity against RT and IN at low nanomolar and low micromolar concentrations, respectively. Exceptionally low IC50 values from a cell-based assay were achieved along with remarkably high therapeutic indices. Compound 7 was identified as the best compound of the series (IC50: 24 nM against RT, 4.4 microM against IN, and 10 nM against HIV-1).

The sponge Dysidea fragilis from Pohnpei contained four azacyclopropene derivatives, (4E)-S-dysidazirine [2], which is the optical enantiomer of the known compound dysidazirine [1], (4Z)-dysidazirine [3], (4E)-S-antazirine [4], and (4Z)-antazirine [5]. The structures of the new compounds were elucidated by interpretation of spectral data.