parent toxicity to the host was induced by IM at the said dosage. Discussion Nowadays, natural products play important roles in people,s lives, especially with regard to staying healthy. More than 60% of the currently used drugs are derived from natural sources. In the area of cancer, 62% of small molecules and new chemical entities are from nature. Natural products and their Vorinostat derivatives have been and continue to be rich sources for anticancer drug discovery. A. dahurica, an herb widely used in traditional herbal preparations in China, is characterized by liver protection, antitumor and antimicrobial effects, etc, The main component, coumarin, was highlighted more recently for its various bioactivities such as antibiotic, anticonvulsant, and antiproliferative effects. Among various coumarins isolated from A.
dahurica, IM exhibited a low toxicity to human normal jak stat cell lines and has been reported to have anticonvulsant and anti HIV 1 replication activities. In addition, it has been suggested that IM may play a potential role against cancer when administered orally in the diet. In the study of Pae et al, IM had antiproliferative effects on several cancer cell lines and induced apoptosis in HL 60 cells via the cytochrome c dependent pathway. However, the details underlying the mechanisms of these anticancer effects are not well understood. Apoptosis, or programmed cell death, is considered a vital component of various processes including normal cell turnover, proper development of the immune sys tem, and chemical induced cell death.
Inappropriate apoptosis is a factor in many human Tofacitinib 540737-29-9 conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders, and many types of cancer. Apoptosis is currently considered an efficient strategy for cancer therapy. In the present study, IM showed an antiproliferative effect, which is comparable to the finding of Kim et al. that furanocoumarins from the root of A. dahurica exhibited a significant inhibition on cell proliferation on several human tumor cells. Among the cells examined, IM exhibited a marked inhibition of the growth of HepG2 cells. The results of various biochemical assays demonstrated that IM triggered growth inhibition through apoptosis induction as evidenced by chromatin condensation, DNA fragmentation, and PS externalization. The induction of apoptosis by IM was found to be mediated through both death receptor and mitochondria pathways.
Treatment with IM resulted in significantly JNK Signaling Pathway diminished expressions of procaspase 3, pro caspase 8, and pro caspase 9. Furthermore, the IM induced apoptosis was suppressed by caspase 8 and caspase 9 specific inhibitors. However, in the study of Pae et al. IM induced apoptosis in HL 60 cells was suppressed by caspase 3, and a caspase 9 specific inhibitor, but the caspase 8 inhibitor had no effect. In our study, the IM induced apoptosis in HepG2 imperial cells was blocked by both caspase 8 and caspase 9 specific inhibitors and is believed to be mediated via both caspase 8 and caspase 9. The involvement of the death receptor pathway was further confirmed by the upregulation of Fas and FADD by IM. For the mitochondria pathway, IM treatment had a significant effect on the levels of p21 and p53, which would modulate the expression levels of Bcl 2 family member.