cucurbitacin-d and Carcinoma--Hepatocellular

Cucurbitacin D (CuD) is a natural compound that can be isolated in various plant families, mainly from Ecballium elaterium (L.) A. Rich. (E. elaterium). It is a triterpenoid with a broad spectrum of biological activity, including anti-cancer properties. Hepatocellular carcinoma, the aggressive type of liver cancer, is an important public health problem worldwide.. In the present study, we investigated the anticancer effect of CuD treated at different doses on the HepG2 cell line and the underlying mechanism in vitro.. CuD was isolated from the fruit juice of E. elaterium plant, and quantitative analysis was performed using high-performance liquid chromatography. The cell viability effect of purified CuD was determined by the MTT test, and also cell apoptosis and cell cycle arrest effects were determined by flow cytometry. DNA damage was evaluated with the comet test. Proteins and genes involved in PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 signaling pathways were evaluated by western blot and qRT-PCR.. CuD showed both antiproliferative and cytotoxic effects against the HepG2 cell line in a dose and time-dependent manner. It was observed that CuD induced apoptosis and blocked the cell cycle in HepG2 cells. It was observed that the expressions of genes and some proteins that play a key role in PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 cascades were dose-dependently downregulated and led to activatation of the apoptotic pathway.. All these results show promise that CuD may have a therapeutic effect in hepatocellular carcinoma.

Topics: Apoptosis; Carcinoma, Hepatocellular; Cell Proliferation; Hep G2 Cells; Humans; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; STAT3 Transcription Factor; TOR Serine-Threonine Kinases; Triterpenes

The aim of the present study is to examine the effects of the anti-tumor component isolated from Trichosanthes kirilowii on human hepatocellular carcinoma cells. Using Sephadex G-25 column chromatography, Sep-Pak Plus C18 cartridge and high-performance liquid chromatography (HPLC), we isolated the active component from trichosanthes extract. By fast atom bombardment mass spectrometric analysis, the molecular mass of the active fraction was determined, the active components identified, and their mechanisms of action were analyzed by cell growth assay, cell cycle analysis, TUNEL staining and Western blot analysis. We found that the anti-tumor components isolated from the extract of trichosanthes (EOT) are cucurbitacin D and dihydrocucurbitacin D, and suggest that cucurbitacin D induces apoptosis through caspase-3 and phosphorylation of JNK in hepatocellular carcinoma cells. These results suggest that cucurbitacin D isolated from Trichosanthes kirilowii could be a valuable candidate for anti-tumor drug.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Caspase 3; Cell Line, Tumor; Cell Proliferation; Humans; Liver Neoplasms; MAP Kinase Kinase 4; Medicine, Traditional; Plant Roots; Trichosanthes; Triterpenes