The clerodane diterpene casearin J induces apoptosis of T-ALL cells through SERCA inhibition, oxidative stress, and interference with Notch1 signaling.
De Ford C, Heidersdorf B, Haun F, Murillo R, Friedrich T, Borner C, Merfort I.
Cell Death Dis. 2016 Jan 28;7:e2070
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28.01.2016
De Ford C, Heidersdorf B, Haun F, Murillo R, Friedrich T, Borner C, Merfort I.
Cell Death Dis. 2016 Jan 28;7:e2070
Cell Death Dis. online article
We show that both thapsigargin (Tg) and the natural product clerodane diterpene casearin J inhibit the SERCA pump and induce intrinsic apoptosis via ER calcium depletion. However, in contrast to Tg, casearin J preferentially kills T-cell acute lymphoblastic leukemia (T-ALL) cells because they express auto-activating Notch mutants that do not properly function after treatment. Therefore casearin J is a novel Tg-derivative specifically targeting cancer cells with activating Notch mutations.
