| In Vivo | HS-1793 (5 and 10 mg/kg; i.p.; twice a week, 4 weeks) significantly inhibits MDA-MB-231 xenograft tumor growth and in a dose-dependent manner and relatively hampers angiogenesis with non-toxicity. Animal model: Five-week-old female BALB/c nude mice injected with MDA-MB-231 cells. Dosage: 5 mg/kg and 10 mg/kg (dissolved in PBS containing 0.1% v/v dimethyl sulfoxide (DMSO)). Administration: Intraperitoneal injection, twice a week, 4 weeks. Result: Significantly inhibited MDA-MB-231 xenograft tumor growth in a dose-dependent manner with non-toxicity. Significantly lowered Ki-67 (a proliferation marker) and CD31 expression. Successfully suppressed the expression of HIF-1α and VEGF in tumor tissues. |
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| In Vitro | HS-1793 (0-100 μM; 24 h) suppresses proliferation of MCF-7, MDA-MB-231 and HCT116 cells. HS-1793 (0-50 μM; 4 h) inhibits hypoxia-induced HIF-1α protein in MCF-7 and MDA-MB-231 cells unrelated to cell death, downregulates hypoxia-induced VEGF expression, and suppresses hypoxia-induced mRNA expression of VEGF at the transcriptional level. HS-1793 (0-100 μM; 24 h) induces apoptosis, promotes G2/M cell cycle arrest, and inhibits Akt and ERK phosphorylation in HCT116 cells. Cell Proliferation Assay Cell line: MCF-7, MDA-MB-231 and MCF-10A. Concentration: 0-100 μM. Incubation time: 24 h. Result: Showed antiproliferation activity with IC50 values of 26.3±3.2, 48.2±4.2 and >100 μM against MCF-7, MDA-MB-231 and MCF-10A, respectively. Western blot analysis. Cell line: MCF-7, MDA-MB-231. Concentration: 12.5, 25 and 50 μM Incubation time: 4 h. Result: Downregulated HIF-1α expression in a concentration-dependent manner in both cell lines. RT-PCR Cell line: MCF-7, MDA-MB-231. Concentration: 12.5, 25 and 50 μM Incubation time: 4 h. Result: Downregulated the expression of VEGF mRNA, with the more marked results observed in MDA-MB-231 cells. Cell Proliferation Assay Cell line: HCT116. Concentration: 12.5, 25, 50 and 100 μM Incubation time: 1, 2 and 4 days. Result: Significantly reduced the cell viability concentration- and time-dependently. Significantly suppressed proliferation of colon cancer cell line HCT116.Apoptosis Analysis Cell line: HCT116. Concentration: 12.5, 25, 50 and 100 μM Incubation time: 24 h. Result: Induced cell apoptosis in a dose-dependent manner. Caused chromatin condensation and fragmentation. Western blot analysis. Cell line: HCT116. Concentration: 12.5, 25, 50 and 100 μM Incubation time: 24 h. Result: Effectively induced the reduction of pro-caspase-8 and pro-caspase-3 at 100 μM. Activated caspase-8 and caspase-3. Caused the PARP cleavage. Slightly downregulated the level of antiapoptotic protein Bcl-2 at 100 μM. Promoted an increase in the release of cytochrome c from the mitochondria into the cytosol. Decreased the expression of G2/M cell cycle regulatory protein cyclin B1, Cdc2 and Cdc25C. Decreased the level of CDK4 and CDK6. Decreased Akt phosphorylation and reduced total Akt at high-concentration. |
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