Growth Inhibition and Apoptosis-Induced Effect on Human Cancer Cells of Toosendanin, a Triterpenoid Derivative from Chinese Traditional Medicine

Abstract

Toosendanin, a triterpenoid derivative isolated from the barks of Melia toosendan Sieb et Zucc, has been used as an anthelmintic vermifuge against ascaris for more than fifty years in China. In the present study, we investigated the growth inhibition and apoptosis-induced effect of toosendanin on human cancer cells. The result showed that toosendanin significantly suppressed the proliferation of tested human cancer cell lines. The IC(50) values were less than 1.7 x 10(-7) M and U937 was the most sensitive cell line with a IC(50) of 5.4 x 10(-9) M. Flow cytometric analysis revealed that treatment of U937 cells with toosendanin resulted in a dose- and time-dependent accumulation of cells in the S phase with a concomitant decrease in cells processing to G(0)/G(1) phase. The growth inhibition of U937 cells after exposure to toosendanin was subsequently associated with the induction of apoptosis, as evidence by the typical condensed and fragmented nuclei, DNA fragmentation, and exposure of phosphatidylserine on the outer leaflet of plasma membrane. All these results indicated that toosendanin could serve as a potential candidate for anticancer drug.

Inhibitory Effect of a Triterpenoid Compound, with or without Alpha Interferon, on Hepatitis C Virus Infection

“…TSN has been used as an anthelmintic vermifuge against ascaris (31). Although TSN has some other biological effects against toxin-producing anaerobic bacteria and against carcinoma cells (32,45), antiviral activity has not been reported.…”

“…TSN has been used as an anthelmintic vermifuge against ascaris (31). Although TSN has some other biological effects against toxin-producing anaerobic bacteria and against carcinoma cells (32,45), antiviral activity has not been reported.In this study, we showed, using an HCV replicon system, that TSN, with or without ␣-IFN, inhibits HCV replication in a cultured human hepatoma Huh7 cell line and that the combination of TSN and ␣-IFN shows synergistic effects on viral replication. We have investigated the mechanisms of action of…”

Roles of reactive oxygen species and MAP kinases in the primary rat hepatocytes death induced by toosendanin

“…It has been reported that toosendanin selectively blocks acetylcholine (ACh) release from nerve terminals and has antibotulismic role in vitro and in vivo (Shi and Chen, 1999;Zhou et al, 2003;Shi and Wang, 2004). Recently, toosendanin-induced apoptosis on various cancer cells was reported (Tang et al, 2004;Zhang et al, 2005). However, liver injury was reported when toosendanin or Melia-family plants which contain toosendanin were used in traditional Chinese medicine.…”

“…The death receptor pathway and the mitochondrial pathway have been reported in apoptotic death of mammalian cells (Hengartner, 2000;Wang, 2001). It has been reported that toosendanin can induce cytochrome c release and caspase-3 activation in PC12 and cancer cells (Tang et al, 2004;Zhang et al, 2005).…”

Tetraploids Isatis indigotica are more responsive and adaptable to stresses than the diploid progenitor based on changes in expression patterns of a cold inducible Ii CPK1

“…It is known to treat the cause of a disease rather than to alleviate its symptoms (Siow et al 2005). And Chinese traditional herb can be used to treat many diseases, such as cancer (Zhang et al 2005), diabetes (Wu et al 2002), bacterial infection (Xie et al 2004) and others.…”