ABSTRACT
Hepatocellular carcinoma (HCC) is the most common tumor in worldwide and chemotherapy resistant is a severe obstacle in HCC treatment. Annonaceous acetogenins was a nature compound from Uvaria accuminata and it has show the anti-tumor proliferation activity in many types cancer. In this study, we showed that annonaceous acetogenins is correlated with the drug resistance reversal in human hepatocellular carcinoma BEL-7402/5-FU and HepG2/ADM cell lines. We found that cell apoptosis was improved and cell cycle was arrested, further, multidrug-resistance proteins such as MDR1, MRP1, Topo-IIα, GST-π, cyclin D1, Survivin and bcl-2 are down-regulated, however, intracellular Rh-123 and caspase-3/8 was up-regulated by Annonaceous acetogenins treatment. We also found that there was a decreased activity of NF-κB and Akt in Annonaceous acetogenins treatment groups. Therefore, we demonstrate that Akt/NF-κB pathway was involved in Annonaceous acetogenins reverses drug resistance of human hepatocellular carcinoma cells.
Subject(s)
Acetogenins/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Hepatocellular/drug therapy , Drug Resistance, Neoplasm/drug effects , Liver Neoplasms/drug therapy , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Cycle Checkpoints/drug effects , Cell Cycle Proteins/metabolism , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Hep G2 Cells , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effectsABSTRACT
In the title compound, C(16)H(10)ClFN(2), the dihedral angle between the indole ring system and the benzyl ring is 80.91â (5)°. The crystal packing features C-Hâ¯Cl, C-Hâ¯F and C-Hâ¯π inter-actions.
ABSTRACT
In the title compound, C(16)H(12)N(2), the dihedral angle between the indole ring system and the pendant phenyl ring is 64.92â (5)°. The crystal packing features aromatic π-π stacking [centroid-centroid separation = 3.9504â (9)â Å] and C-Hâ¯π inter-actions.
