Study On The Mechanism Of Programmed Cell Death In Human Lung Adenocarcinoma And Heptocarcinoma Cells Induced By Trichokonin Ⅵ

Cancer is a major threat to human health and its morbidity is increasing in recent years. Hepatocellular carcinoma and lung cancer are two kinds of typical cancer which are hard to cure. Moreover, the nosogenesis of the cancer is very complicate. In the therapy of cancer, antibiotics are a major source of chemotherapeutic agents. Trichokonins (TKs) are a type of peptaibols secreted by Trichoderma pseudokoningii SMF2 conserved in our lab, which mainly include three kinds:TrichokoninⅥ, TrichokoninⅦand TrichokoninⅦ. TrichokoninⅥhas the ability to form calcium channel on bullfrog cardiac myocyte membrane. Based on the previous studies, the anticancer activity and mechanism of antitumor involved in TrichokoninⅥwere investigated. The findings demonstrated that human lung carcinoma cancer A549 cells and hepatocellular carcinoma HepG2 cells treated with TrichokoninⅥunderwent apoptosis accompanied with autophagy. TrichokoninⅥtriggered features of apoptosis in the two cell lines including phosphoserine exposure, DNA fragmentation and DNA ladder. Meanwhile, features of autophagy were also assessed by formation of autophagosomes and processing of microtube-associated protein 1 light chain 3 (LC3) typeⅠtoⅡin the two cell lines treated with TrichokoninⅥ. In order to investigate the antitumor mechanisms involved in TrichokoninⅥ, we chose A549 cells as a model to detail the process. Our results showed that both the apoptosis and autophagy in A549 were independent of caspases activity. In detail, the expression of Bcl-xL decreased and expression of Bax increased, suggesting that mitochondria inner membrane Bcl-2 protein family may play an important role in this process. At the same time, mitochondria membrane potential dissiapation (△Ψm) and reactive oxygen species (ROS) increase were detected in A549 treated with TrichokoninⅥ. Our results first showed the mechanism involved in peptaibols to induce apoptotic and autophagic cell death in lung cancer cells.