Combining in vitro and in ovo assays to screen for anti-cancer and anti-angiogenic effects of the leaf extracts of Mallotus cumingii Müll.Arg. (Euphorbiaceae)

Cancer treatment is often challenging and various interventions may have detrimental effects. Due to this, the development of less harmful alternatives such as herbal medicine is essential. The present study aims to determine the leaf phytoconstituents present and the bioactivities of Mallotus cumingii Müll.Arg against cancer cells through the utilization of MTT assay and anti-angiogenesis through CAM assay. The leaf extracts obtained three fractions namely, methanolic crude (MCME) extracts, hexane extracts (MCHE), and ethyl acetate extracts (MCEA), and was tested on HCT-116 for in vitro cytotoxicity, and blood vessel density and branching through in ovo CAM assay. Phytochemical analysis showed that the M. cumingii fractions contain phenolic compounds, terpenoids, cardiac glycosides, flavonoids, and saponins. For in vitro set-up, MCME of M. cumingii were separated into MCHE and MCEA partitions and were tested against HCT-116 and obtained an IC50 value of < 30 μg/mL, which is deemed active in cytotoxicity. For in ovo set-up, two concentrations of each extract were applied to the duck eggs. Blood vessel density and number of branching points were measured through the ImageJ analysis. All extracts exhibited antiangiogenic activity, either by decreasing blood vessel density or the number of branching points. Overall, the study demonstrates the potential of M. cumingii as a source of therapeutic agents

Enobosarm (GTx-024) modulates adult skeletal muscle mass independently of the androgen receptor in the satellite cell lineage

Androgens increase skeletal muscle mass, but their clinical use is hampered by lack of tissue selectivity and subsequent side-effects. Selective androgen receptor modulators (SARMs) elicit muscle-anabolic effects while only sparingly affecting reproductive tissues. The SARM GTx-024 (enobosarm) is being investigated for cancer cachexia, sarcopenia, and muscle wasting diseases. Here, we investigate the role of muscle androgen receptor (AR) in the anabolic effect of GTx-024. In mice lacking AR in the satellite cell lineage (satARKO), the weight of the androgen-sensitive levator ani muscle was lower, but decreased further upon orchidectomy. GTx-024 was as effective as dihydrotestosterone (DHT) in restoring levator ani weights to sham levels. Expression of the muscle-specific androgen-responsive genes S-adenosylmethionine decarboxylase and myostatin was decreased by orchidectomy and restored by GTx-024 and DHT in control mice, while expression was low and unaffected by androgen status in satARKO. In contrast, insulin-like growth factor IEa expression was not different between satARKO and control muscle, decreased upon castration, and was restored by DHT and GTx-024 in both genotypes. These data indicate that GTx-024 does not selectively modulate AR in the satellite cell lineage and that cells outside this lineage remain androgen-responsive in satARKO muscle. Indeed, residual AR positive cells were present in satARKO muscle, coexpressing the fibroblast-lineage marker vimentin. AR positive, muscle-resident fibroblasts could therefore be involved in the indirect effects of androgens on muscle. In conclusion, both DHT and GTx-024 target AR pathways in the satellite cell lineage, but cells outside this lineage also contribute to the anabolic effects of androgens.status: publishe

マウス タイシ キュウカイメンタイキン ケイセイ カテイ ニ オケル アンドロゲン レセプター オ カイシタ アラタナ セイサ ケイセイ メカニズム

熊本大