Fig. 1.

Celastrol downregulates NPM1-ALK fusion protein and its signaling: (a) celastrol treatment depletes NPM1-ALK protein levels and inhibits activation of NPM1-ALK fusion kinase. NPM1-ALK expressing SUDHL-1, Karpas-299, SUP-M2, SR-786, DEL, and Ba/F3-FG-NPM1-ALK cells were treated with indicated concentrations of celastrol for 24 h. At the end of the treatment period, cell lysates were made, and immunoblot analyses were performed for total NPM1-ALK and phospho-NPM1-ALK proteins. b Depletion of NPM1-ALK leads to inhibition of downstream survival signaling cascade. NPM1-ALK expressing ALCL cell lines treated with celastrol and western blot analyses were performed for downstream effector molecules pSTAT3, pAKT, pERK1/2 along with total proteins. β-actin served as the loading control