The aqueous extract of the Argentinean native plant, Prosopis strombulifera (PsAE), presents cytotoxicity against human cancer cell lines by inducing cytostasis, necrosis and apoptosis; with diminution of clonogenic survival; without genotoxic effects nor oral animal toxicity. Until now, the chemical extract composition and its in vivo antitumoral properties remain unknown; these studies are the aim of the current work. The PsAE was characterized by chemical fingerprinting and the metabolome was identified by tandem UHPLC-PDA-HESI-Q-orbitrap® mass spectrometry. Colorectal tumors were induced by DMH administration and melanomas resulted from B16-F0 S.C. cells injection; then, animals were treated orally with PsEA. To correlate in vivo results with in vitro cytotoxicity, B16-F0 cell were cultured to determine: cell proliferation and viability by dye exclusion assays, MTT and CFSE dilution; cell cycle distribution by flow cytometry; and immunoblotting of p21 cip1 , PCNA, cleaved caspase 3, cleaved PARP and TUBA1A. Based on UHPLC-OT-MS and PDA analysis, twenty-six compounds were identified, including: 5 simple organic acids, 4 phenolic acids, 4 procyanidins, 11 flavonoids, and 2 oxylipins. On C57BL6 mice, PsAE significantly increases the median survival on colorectal cancer and reduces the final volume and weight of melanomas. Over cultured cells, the treatment induce over-expression of p21, cytostasis by G2/M cell cycle arrest and apoptosis; while, on in vivo melanomas, treatment up-regulates p21 and slightly decreases PCNA. In conclusion, PsAE is composed by phenolic compounds which demonstrate cytotoxic and antitumoral properties when is orally administrated. Presented results support future research of PsAE as a potential phytomedicine for cancer treatment.
<b><i>Introduction:</i></b> The potential of the thyroid hormone receptor β (TRβ1) selective analog GC-1 has been widely proven in animal models and humans. However, its effect on the reproductive stage of the female rat has not been evaluated. <b><i>Methods:</i></b> The effect of the administration of GC-1 or equimolar doses of triiodothyronine (T3) was evaluated on the reproductive performance of the hypothyroid female rat and the indirect effect on pup thyroid status, weight, and survival. <b><i>Results:</i></b> Hypothyroidism reduced the number of embryos implanted in the uterus, whereas T3 and GC-1 treatment in hypothyroid females reestablished the number of implanted embryos to normal. Initiation of labor was delayed by hypothyroidism, and T3 replacement treatment reinstated the normal timing of parturition. The administration of GC-1 alone to the lactating mother did not affect pup survival, weight, or thyroidal status. <b><i>Conclusions:</i></b> Our findings show the differential effect of thyroid hormone selective signaling during gestation and the indirect exposure of the pups; we also emphasize the plausible use of GC-1 for treatment of hypothyroid mothers during the lactation period.
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