S-phase arrest and apoptosis in human breast adenocarcinoma MCF-7 cells via mitochondrial dependent pathway induced by tricyclohexylphosphine gold (I) n-mercaptobenzoate complexes.

We have previously reported the inhibition of thioredoxin reductase (TrxR) and invasion by tricyclohexylphosphine gold (I) n-mercaptobenzoate (n = 2, 3, 4) labeled as 1-3 towards MCF-7 cells, in vitro. Nevertheless, the mode of death and its apoptotic pathway has yet to be revealed. The main aim of this study is to investigate the anti-neoplastic activity of this phosphanegold (I) thiolates against breast adenocarcinoma cells, MCF-7. Herein, we explored the role of gold(I) series, 1-3 for their apoptosis-inducing ability against MCF-7 cells. They were scrutinized for their antiproliferative activities which exhibited their IC50 values of 8.14 µM ± 0.10, 7.26 µM ± 0.33, and 9.03 µM ± 0.69, respectively, and indicated better cytotoxicities than that of cisplatin (positive control). Further, the mechanisms of their actions were studied by analyzing the status of ROS generation (by DCFH-DA), cytochrome c release (by ELISA), and activation of caspases 3/7, 8, 9, and 10, annexin V staining and cell cycle analysis by flow cytometry, respectively. It was observed that the compounds, 1-3 can promote ROS generation, cytochrome c release, and activation of caspases 3/7, caspase 8, caspase 9, and caspase 10 on MCF-7 cells. In addition, the compounds are shown to induce MCF-7 cell arrest at S-phase. Gene analysis via PCR array further clarified their effects by modulating the related genes upon the compounds' treatment. Further investigation on other breast cancer cells as well as in vivo studies on these compounds will further increase their potential as anti-breast cancer agents.

Evaluation of anti-inflammatory activities of ethanolic extract of Annona muricata leaves

Traditionally, the leaves of Annona muricata L., Annonaceae, are used to treat headaches, fever, toothache, cough and asthma. The decoction of the leaves has parasiticide, antirheumatic and antineuralgic effects when used internally, while the cooked leaves, applied topically, fight rheumatism and abscesses. The aim of this study was to investigate acute and chronic anti-inflammatory potential of an ethanolic leaf extract of A. muricata (AML) in animal models. The ethanolic extract of A. muricata leaf extract was prepared and administered orally to experimental animals used. The anti-inflammatory activity was determined by xylene-induced ear edema in mice and Complete Freund's adjuvant (CFA)-induced arthritis in rats. The results demonstrated that AML is effective for both acute and chronic inflammation. It also significantly attenuated both TNF-α and IL-1β levels in CFA-induced arthritis model. Thus, these results have suggested that AML possesses both anti-inflammatory and anti-arthritic activities. The findings also suggest that AML presents notable anti-arthritic activity that may be mediated by suppressing pro-inflammatory cytokines.

Antinociceptive and anti-ulcerogenic activities of the ethanolic extract of Annona muricata leaf

Ethanolic extract of Annona muricata L., Annonaceae, leaf (AML) was used to investigate its antinociceptive and anti-ulcerogenic activities and the involvement of the mechanism of ethanolic leaves extract of AML in various animal models. Antinociceptive activity of AML extract was done using acetic acid-induced abdominal writhing in mice, formalin test in rats and hot plate test in mice. Furthermore, the anti-ulcerogenic effect of AML extract was studied in ethanol-induced ulcer model in rats, ethanol-induced gastric lesions in L-NAME-pre-treated rats as well as ethanol-induced gastric lesions in NEM-pre-treated rats test model to determine its mechanism. AML exhibited significant and dose-dependent antinociceptive activity. It also significantly decreased the ulcerative lesion produced by ethanol in rats in a dose-dependent manner. Pre-treatment with N-ethymaleimide, a thiol blocker, including mucosal nonprotein sulfhydryl groups, reduced the anti-ulcerogenic effect of AML extract in the same ulcer model, suggesting that AML extract may have active substances such as tannins, flavanoids and triterpenes that increase the mucosal nonprotein sulfhydryl group content.