Narrow Results

This study was conducted to explore the abortifacient effect and the mechanisms of the Chinese herbal medicine component toosendanin, and to elucidate the significance of the Th1 cytokines IFN-γ and TNF-α, CD4+ and CD8+ T lymphocytes in the occurrence of abortion. Graded doses of toosendanin were given by intraperitoneal injection (i.p.) to mice at day 5, 6, 7 of gestation. The levels of Th1 cytokines (IFN-γ, TNF-α) in serum and uterine tissues from mice sacrificed at day 8 were analyzed by enzyme linked immunosorbent assay (ELISA). Presence of T lymphocytes in endometrium was detected by immunohistochemistry. The results revealed that injection of toosendanin could produce a dose-dependent toxicity. The IFN-γ, TNF-α content in serum and uterine tissues were increased significantly. The CD4+ and CD8+ T lymphocytes were also increased in the endometrium of toosendanin treated groups. In conclusion, toosendanin is pregnancy-toxic to animals and it is relevant to the increased contents of IFN-γ, TNF-α and CD4+, CD8+ T lymphocytes.

Toosendanin (TSN) is a triterpenoid extracted from the bark or fruits of Melia toosendan Sieb et Zucc, which is a traditional Chinese medicine and mainly grows in China and India. TSN has been verified to possess antitumor activities on various human cancers, whereas the effects of TSN on ovarian cancer (OC) has not been reported yet. Here, TSN was shown to significantly inhibit proliferation of SKOV3 and OVCAR3 cell lines in a dose- and time-dependent manner. Treatment of OC cells with TSN resulted in colony formation reduction, S and G2/M phase arrest, cell apoptosis, and dramatic decrease in mitochondrial membrane potential. Furthermore, TSN suppressed invasion and migration of OC cells. Research on molecular mechanism indicated that the above efficacy of TSN was associated with decreased expression of survivin, PARP-1, Bcl-2, Bcl-xl, caspase-3, caspase-9, MMP-2 and MMP-9 and increased expression of cleaved PARP-1, Bax, cleaved caspase-3 and cleaved caspase-9. Finally, in vivo results showed that TSN suppressed OC xenograft tumor growth by inducing apoptosis and regulating the related protein expression levels of SKOV3 cells in transplanted tumors. Taken together, our data provide new insights into TSN as a potentially effective reagent against human OC through caspase-dependent mitochondrial apoptotic pathway.