Triterpenoid saponin flaccidoside II from Anemone flaccida triggers apoptosis of NF1-associated malignant peripheral nerve sheath tumors via the MAPK-HO-1 pathway.
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue neoplasms that are extremely rare and are frequently associated with neurofibromatosis type 1 patients. MPNSTs are typically fatal, and there is no effective treatment so far. In our previous study, we showed that flaccidoside II, one of the triterpenoid saponins isolated from Anemone flaccida Fr. Schmidt, has antitumor potential by inducing apoptosis. In the present study, we found that flaccidoside II inhibits proliferation and facilitates apoptosis in MPNST cell lines ST88-14 and S462. Furthermore, this study provides a mechanism by which the downregulation of heme oxygenase-1 via extracellular signal-regulated kinase-1/2 and p38 mitogen-activated protein kinase pathways is involved in the apoptotic role of flaccidoside II. This study suggested the potential of flaccidoside II as a novel pharmacotherapeutic approach for MPNSTs.
China Key Laboratory of TCM Resource and Prescription, Ministry of Education, Wuhan, Hubei, People's Republic of China.
Lin-Tao
LT
Han
China Key Laboratory of TCM Resource and Prescription, Ministry of Education, Wuhan, Hubei, People's Republic of China.
Yin
Y
Fang
Department of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, People's Republic of China.
Yan
Y
Cao
China Key Laboratory of TCM Resource and Prescription, Ministry of Education, Wuhan, Hubei, People's Republic of China.
Feng-Hua
FH
Wu
Department of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, People's Republic of China.
E
E
Liu
Department of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, People's Republic of China.
Guo-Yan
GY
Mo
China Key Laboratory of TCM Resource and Prescription, Ministry of Education, Wuhan, Hubei, People's Republic of China.
Fang
F
Huang
HO-1; MAPK; apoptosis; flaccidoside II; malignant peripheral nerve sheath tumors