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      Anti-human hepatoma Hep-G2 proliferative, apoptotic, and antimutagenic activity of tagitinin C from Tithonia diversifolia leaves.

      Journal of Natural Medicines
      Animals, Antimutagenic Agents, chemistry, pharmacology, therapeutic use, Apoptosis, drug effects, Asteraceae, Female, Hep G2 Cells, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Plant Extracts, Plant Leaves, Sesquiterpenes, Xenograft Model Antitumor Assays

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          Abstract

          Tagitinin C, a major sesquiterpenoid, was isolated from the leaves of Tithonia diversifolia. The high morbidity and mortality rate of hepatoma in Taiwan motivated our interest in the investigation of tagitinin C's mechanism against the human hepatocellular carcinoma. The methanolic extract of leaves of T. diversifolia (TDM) and tagitinin C were found to have cytotoxic activities against human hepatoma Hep-G2 cells in the MTT assay with IC(50) values of 40.0 ± 2.0 and 2.0 ± 0.1 μg/mL, respectively. This compound induced population increase in the sub-G(1) phase and S phase arrest. Treatment with tagitinin C isolated from TDM resulted in activation of both caspase 3 and caspase 8 which suggested that the antiproliferative effect of this compound was caspase-dependent apoptosis. Magnetic resonance techniques indicated that the tumorigenisity of xenografts derived from Hep-G2 cells was retarded by the delivery of tagitinin C (15 μg/mouse/day) relative to the control counterparts.

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