@article{PAR00010314,
  title = {{S}imalikalactone {E} ({S}k{E}), a new weapon in the armamentarium of drugs targeting cancers that exhibit constitutive activation of the {ERK} pathway},
  author = {{R}obert, {G}. and {J}ullian, {V}al{\'e}rie and {J}acquel, {A}. and {G}inet, {C}. and {D}ufies, {M}. and {T}orino, {S}. and {P}ottier, {A}. and {P}eyrade, {F}. and {T}artare-{D}eckert, {S}. and {B}ourdy, {G}enevi{\`e}ve and {D}eharo, {E}ric and {A}uberger, {P}.},
  editor = {},
  language = {{ENG}},
  abstract = {{S}imalikalactone {E} ({S}k{E}) is a quassinoid extracted from a widely used {A}mazonian antimalarial remedy. {A}lthough {S}k{E} has previously been shown to have cytostatic and/or cytotoxic activities in some tumor cell lines, its mechanism of action has not yet been characterized. {W}e show here that {S}k{E} in the high nanomolar range inhibited the growth of various leukemic and solid tumor cell lines. {I}mportantly, {S}k{E} was highly efficient at inhibiting chronic myelogenous leukemia ({CML}) cells that exhibit constitutive activation of the {MAPK} pathway and, accordingly, it impaired the phosphorylation of {ERK}1/2. {S}k{E} also abrogated {MEK}1/2 and {B}-{R}af phosphorylation but had no effect on {R}as activity. {M}oreover, {S}k{E} was particularly effective against melanoma cell lines carrying the {B}-{R}af-{V}600{E} mutation. {I}mportantly, {S}k{E} resensitized the {PLX}-4032-resistant 451{L}u melanoma cell line (451{L}u-{R}) and was more efficient than {U}0126, a {MEK} inhibitor, and {PLX}-4032 ({PLX}) at inducing the apoptosis of two {H}airy {C}ell {L}eukemia ({HCL}) patient samples carrying the {B}-{R}af-{V}600{E} mutation. {F}inally, {S}k{E} was as efficient as imatinib at inhibiting tumor formation in a xenograft model of {CML} cells in athymic mice. {I}n conclusion, we show that {S}k{E}, a very potent inhibitor of {B}-{R}af-{V}600{E}, is highly effective against cancer cell lines that exhibit constitutive activation of the {ERK}1/2 pathway.},
  keywords = {{S}imalikalactone {E} ; {B}-{R}af inhibitor ; {CML} ; {M}elanoma ; {H}airy {C}ell {L}eukemia ; {ERK} pathway},
  booktitle = {},
  journal = {{O}ncotarget},
  volume = {3},
  numero = {12},
  pages = {1688--1699},
  ISSN = {1949-2553},
  year = {2012},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00010314},
}