The effects of policosanol (50-500 mg/kg) administered orally for 24 months to Sprague Dawley rats of both sexes were investigated. No differences related to daily clinical observations, weight gain, food consumption, or mortality (survival analysis) between groups were found. Histopathological study showed that the frequency of the occurrence of non-neoplastic and neoplastic (benign and malignant) lesions was similar in the control and policosanol-treated groups. The lesions observed in this study were similar to the spontaneous lesions reported in this species in previous studies. Since no drug-related increase in the occurrence of malignant or benign neoplasms was found, nor acceleration in tumors growth in any specific group was observed, this study shows no evidence of policosanol induced carcinogenicity in this strain of rats.
Marine plants have become an inexhaustible reservoir of new phytopharmaceuticals for cancer treatment. We demonstrate in vitro/in vivo antitumor efficacy of a standardized polyphenol extract from the marine angiosperm Thalassia testudinum (TTE) in colon tumor cell lines (RKO, SW480, and CT26) and a syngeneic allograft murine colorectal cancer model. MTT assays revealed a dose-dependent decrease of cell viability of RKO, CT26, and SW480 cells upon TTE treatment with IC50 values of, respectively, 175, 115, and 60 μg/mL. Furthermore, TTE significantly prevented basal and bFGF-induced angiogenesis in the chicken chorioallantoic membrane angiogenesis assay. In addition, TTE suppressed bFGF-induced migration of endothelial cells in a wound closure assay. Finally, TTE treatment abrogated CT26 colorectal cancer growth and increased overall organism survival in a syngeneic murine allograft model. Corresponding transcriptome profiling and pathway analysis allowed for the identification of the mechanism of action for the antitumor effects of TTE. In line with our in vitro/in vivo results, TTE treatment triggers ATF4-P53-NFκB specific gene expression and autophagy stress pathways. This results in suppression of colon cancer cell growth, cell motility, and angiogenesis pathways in vitro and in addition promotes antitumor immunogenic cell death in vivo.
Clusia minor L. is traditionally used to treat many disorders that including pain and inflammation such as sores and warts. Four extracts from the leaves of plant were prepared: hexane (CMH-A), ethyl acetate (CMH-B), methanol (CMH-C) and ethanol (CMH-E) and the pharmacological (antioxidant and anti-inflammatory properties) and toxicity effects were examined. Previously, the main constituents from CMH-A extract was revealed. Here, we present the GC/MS analysis of CMH-B and CMH-C. Thirty three compounds were identified in the CMH-B extract and twenty seven compounds in the CMH-C. The presence of D-α-tocopherol and lupeol was relevant in both extracts. The only sterols identified were sitosterol and stigmasterol. All of them showed effective radical scavenger properties in the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay, being CMH-E extract the most promissory (IC50 = 10.25 µg/mL). CMH-A, C and E extracts, administered topically (0.5–4 mg per ear), significant reduced ear edema induced by croton oil at 4 mg per ear, meanwhile CMH-B that was be able to significant reduce the inflammation at the dose of 2 mg per ear. We evaluated also the cytotoxic activity of the extracts against kidney cells (BHK), colon cancer (CT26), endothelial cancer cells (EA.hy926) and breast cancer (4T1). CMH-B extract showed the most cytotoxicity effect, with IC50 values in the range of 32.01-203.5 µg/mL. In addition, no oral acute toxicity after mice exposure to Clusia minor L. extracts was observed. The results suggest Clusia minor L. may be a good potential source of new bioactive agents for developing medicinal agents.
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