Supplementary Materials

Supplementary Materials for:

ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases

C. Leah B. Kline, A. Pieter J. Van den Heuvel, Joshua E. Allen, Varun V. Prabhu, David T. Dicker, Wafik S. El-Deiry*

*Corresponding author. E-mail: wafik.eldeiry{at}fccc.edu

This PDF file includes:

  • Fig. S1. The broad-spectrum anticancer activity of ONC201 can be attributed to its antiproliferative and proapoptotic effects.
  • Fig. S2. ONC201 activates ATF4 and CHOP.
  • Fig. S3. The differential response of ONC201-sensitive and ONC201-resistant lines to ER stress inducers is correlated with ATF4 pathway activation.
  • Fig. S4. ONC201 induces a decrease in cyclin D1 abundance but not in Akt and ERK phosphorylation.
  • Fig. S5. ONC201 does not activate the eIF2α-ATF4 pathway by inhibiting the eIF2α phosphatase or by activating GCN2 or PERK.
  • Fig. S6. The abundance of cIAP-2 and Bcl-2 family members is similarly altered regardless of whether cells undergo apoptosis.
  • Fig. S7. Altering the amount of XIAP does not change ONC201's effects on PARP cleavage.
  • Table S1. ONC201 concentrations used according to cell type.
  • Table S2. Top gene expression changes induced by ONC201 in HCT116 cells.
  • Table S3. Top gene expression changes induced by ONC201 in RKO cells.
  • Legends for data file S1 to S7

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1 (Microsoft Excel format). Genes in HCT116 cells with altered expression after 18 hours of ONC201 treatment.
  • Data file S2 (Microsoft Excel format). Genes in HCT116 cells with altered expression after 48 hours of ONC201 treatment.
  • Data file S3 (Microsoft Excel format). Additional information on the genes in data file S2.
  • Data file S4 (Microsoft Excel format). Genes in HCT116 cells with altered expression after 18 or 48 hours of ONC201 treatment.
  • Data file S5 (Microsoft Excel format). Genes in HCT116 cells with altered expression after 18 hours but not 48 hours of ONC201 treatment.
  • Data file S6 (Microsoft Excel format). Genes in parental RKO cells with altered expression after 48 hours of ONC201 treatment.
  • Data file S7 (Microsoft Excel format). Genes in ONC201-resistant RKO cells with altered expression after 48 hours of ONC201 treatment.

[Download Data files S1 to S7]


Citation: C. L. B. Kline, A. P. J. Van den Heuvel, J. E. Allen, V. V. Prabhu, D. T. Dicker, W. S. El-Deiry, ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases. Sci. Signal. 9, ra18 (2016).

© 2016 American Association for the Advancement of Science