Ivalin Induces Mitochondria-Mediated Apoptosis Associated with the NF-κB Activation in Human Hepatocellular Carcinoma SMMC-7721 Cells

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 20; p. 3809
• Main Authors: Han, Zhuo, Liu, Fang-Yuan, Lin, Shi-Qi, Zhang, Cai-Yun, Ma, Jia-Hui, Guo, Chao, Jia, Fu-Juan, Zhang, Qian, Xie, Wei-Dong, Li, Xia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.10.2019; MDPI
• Subjects: Annexin V; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Apoptosis; Apoptosis - drug effects; Asteraceae - chemistry; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; carpesium divaricatum; Caspase 3 - metabolism; Cell growth; Cell Line, Tumor; Chemotherapy; Clinical trials; Cytochrome; Cytochromes c - metabolism; DNA-Binding Proteins - metabolism; Flow cytometry; Fluorescence; Hepatocellular carcinoma; Humans; ivalin; Lactones - chemistry; Lactones - metabolism; Lactones - pharmacology; Lactones - therapeutic use; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; mitochondria-mediated apoptosis; NF-kappa B - metabolism; nf-κb; NF-κB protein; Permeability; Proteins; Reactive Oxygen Species - metabolism; Sesquiterpenes - chemistry; Sesquiterpenes - metabolism; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; Signal Transduction - drug effects; Transcription factors; mitochondria-mediated apoptosis; NF-κB; Ivalin; Carpesium divaricatum; hepatocellular carcinoma
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24203809

Ivalin, a natural compound isolated from , showed excellent microtubule depolymerization activities among human hepatocellular carcinoma in our previous work. Here, we investigated its functions on mitochondria-mediated apoptosis in hepatocellular carcinoma SMMC-7721 cells. DAPI (4',6-diamidino-2-phenylindole) staining, annexin V-fluorexcein isothiocyanate (FITC) apoptosis detection, and western blotting were applied to explore the apoptotic effect of Ivalin. Next, the induction effect of Ivalin on the mitochondrial pathway was also confirmed via a series of phenomena including the damage of mitochondria membrane potential, mitochondria cytochrome c escape, cleaved caspase-3 induction, and the reactive oxygen species generation. In this connection, we understood that Ivalin induced apoptosis through the mitochondrial pathway and the overload of reactive oxygen species. Furthermore, we found that the activation of nuclear factor-κB (NF-κB) and subsequent p53 induction were associated with the apoptotic effect of Ivalin. These data confirmed that Ivalin might be a promising pro-apoptotic compound that can be utilized as a potential drug for clinical treatment.