millepachine and Liver-Neoplasms

Chalcones have a long history of being used for many medical purposes. These are the most prestigious scaffolds in medicine. The potential of Millepachine and its derivatives to treat various malignancies has been demonstrated in this review. The anticancer effects of Millepachine and its derivatives on ovarian cancer, hepatocellular carcinoma, breast, liver, colon, cervical, prostate, stomach, and gliomas are highlighted in the current review. Several genes that are crucial in reducing the severity of the disease have been altered by these substances. They mainly work by preventing tubulin polymerizing. They also exhibit apoptosis and cell cycle arrest at the G2/M phase. Additionally, these compounds inhibit invasion and migration and have antiproliferative effects. Preclinical studies have shown that Millepachine and its derivatives offer exceptional potential for treating a number of cancers. These results need to be confirmed in clinical research in order to develop viable cancer therapies.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Chalcones; Drug Screening Assays, Antitumor; Humans; Liver Neoplasms; Male; Structure-Activity Relationship; Tubulin; Tubulin Modulators

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Hepatocellular; Caspase 3; Chalcones; G2 Phase Cell Cycle Checkpoints; Hep G2 Cells; Humans; Liver Neoplasms; Male; Mice, Inbred BALB C; Mice, Nude; Microtubules; Reactive Oxygen Species; Signal Transduction; Tubulin; Tubulin Modulators; Tumor Burden; Xenograft Model Antitumor Assays

In this study, we reported millepachine (MIL), a novel chalcone compound for the first time isolated from Millettia pachycarpa Benth (Leguminosae), induced cell cycle arrest and apoptosis in human hepatocarcinoma cells in vitro and in vivo. In in vitro screening experiments, MIL showed strong antiproliferation activity in several human cancer cell lines, especially in HepG2 cells with an IC50 of 1.51 µM. Therefore, we chose HepG2 and SK-HEP-1 cells to study MIL's antitumor mechanism. Flow cytometry showed that MIL induced a G2/M arrest and apoptosis in a dose-dependent manner. Western blot demonstrated that MIL-induced G2/M arrest was correlated with the inhibition of cyclin-dependent kinase 1 activity, including a remarkable decrease in cell division cycle (cdc) 2 synthesis, the accumulation of phosphorylated-Thr14 and decrease of phosphorylation at Thr161 of cdc2. This effect was associated with the downregulation of cdc25C and upmodulation of checkpoint kinase 2 in response to DNA damage. MIL also activated caspase 9 and caspase 3, and significantly increased the ratio of Bax/Bcl-2 and stimulated the release of cytochrome c into cytosol, suggesting MIL induced apoptosis via mitochondrial apoptotic pathway. Associated with those effects, MIL also induced the generation of reactive oxygen species. In HepG2 tumor-bearing mice models, MIL remarkably and dose dependently inhibited tumor growth. Treatment of mice with MIL (20mg/kg intravenous [i.v.]) caused more than 65% tumor inhibition without cardiac damage compared with 47.57% tumor reduction by 5mg/kg i.v. doxorubicin with significant cardiac damage. These effects suggested that MIL and its easily modified structural derivative might be a potential lead compound for antitumor drug.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Hepatocellular; CDC2 Protein Kinase; Chalcone; Chalcones; Cyclin B; Cyclin-Dependent Kinases; Cytosol; DNA Damage; Dose-Response Relationship, Drug; Enzyme Activation; Female; Flow Cytometry; G2 Phase Cell Cycle Checkpoints; Hep G2 Cells; Humans; Inhibitory Concentration 50; Liver Neoplasms; Membrane Potentials; Mice; Mice, Inbred BALB C; Mice, Nude; Millettia; Mitochondria; Phosphorylation; Reactive Oxygen Species; Xenograft Model Antitumor Assays