Hydroxycoumarin OT-55 kills CML cells alone or in synergy with imatinib or Synribo: Involvement of ER stress and DAMP release

Aloran Mazumder; Jin Young Lee; Oualid Talhi; Claudia Cerella; Sébastien Chateauvieux; Anthoula Gaigneaux; Che Ry Hong; Hyoung Jin Kang; Youngjo Lee; Kyu Won Kim; Dong Wook Kim; Hee Young Shin; Mario Dicato; Khaldoun Bachari; Artur M.S. Silva; Barbora Orlikova-Boyer; Marc Diederich

doi:10.1016/j.canlet.2018.07.041

Hydroxycoumarin OT-55 kills CML cells alone or in synergy with imatinib or Synribo: Involvement of ER stress and DAMP release

Aloran Mazumder, Jin Young Lee, Oualid Talhi, Claudia Cerella, Sébastien Chateauvieux, Anthoula Gaigneaux, Che Ry Hong, Hyoung Jin Kang, Youngjo Lee, Kyu Won Kim, Dong Wook Kim, Hee Young Shin, Mario Dicato, Khaldoun Bachari, Artur M.S. Silva, Barbora Orlikova-Boyer, Marc Diederich^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

29 Citations (Scopus)

Abstract

We synthetized and investigated the anti-leukemic potential of the novel cytostatic bis(4-hydroxycoumarin) derivative OT-55 which complied with the Lipinski's rule of 5 and induced differential toxicity in various chronic myeloid leukemia (CML) cell models. OT-55 triggered ER stress leading to canonical, caspase-dependent apoptosis and release of danger associated molecular patterns. Consequently, OT-55 promoted phagocytosis of OT-55-treated CML cells by both murine and human monocyte-derived macrophages. Moreover, OT-55 inhibited tumor necrosis factor α-induced activation of nuclear factor-кB and produced synergistic effects when used in combination with imatinib to inhibit colony formation in vitro and Bcr-Abl⁺ patient blast xenograft growth in zebrafish. Furthermore, OT-55 synergized with omacetaxine in imatinib-resistant KBM-5 R cells to inhibit the expression of Mcl-1, triggering apoptosis. In imatinib-resistant K562 R cells, OT-55 triggered necrosis and blocked tumor formation in zebrafish in combination with omacetaxine.

Original language	English
Pages (from-to)	197-218
Number of pages	22
Journal	Cancer Letters
Volume	438
DOIs	https://doi.org/10.1016/j.canlet.2018.07.041
Publication status	Published - 1 Dec 2018
Externally published	Yes

Keywords

Calreticulin
Eukaryotic initiation factor 2α
High mobility group box 1
Phagocytosis

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10.1016/j.canlet.2018.07.041

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Mazumder, A., Lee, J. Y., Talhi, O., Cerella, C., Chateauvieux, S., Gaigneaux, A., Hong, C. R., Kang, H. J., Lee, Y., Kim, K. W., Kim, D. W., Shin, H. Y., Dicato, M., Bachari, K., Silva, A. M. S., Orlikova-Boyer, B., & Diederich, M. (2018). Hydroxycoumarin OT-55 kills CML cells alone or in synergy with imatinib or Synribo: Involvement of ER stress and DAMP release. Cancer Letters, 438, 197-218. https://doi.org/10.1016/j.canlet.2018.07.041

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title = "Hydroxycoumarin OT-55 kills CML cells alone or in synergy with imatinib or Synribo: Involvement of ER stress and DAMP release",

abstract = "We synthetized and investigated the anti-leukemic potential of the novel cytostatic bis(4-hydroxycoumarin) derivative OT-55 which complied with the Lipinski's rule of 5 and induced differential toxicity in various chronic myeloid leukemia (CML) cell models. OT-55 triggered ER stress leading to canonical, caspase-dependent apoptosis and release of danger associated molecular patterns. Consequently, OT-55 promoted phagocytosis of OT-55-treated CML cells by both murine and human monocyte-derived macrophages. Moreover, OT-55 inhibited tumor necrosis factor α-induced activation of nuclear factor-кB and produced synergistic effects when used in combination with imatinib to inhibit colony formation in vitro and Bcr-Abl+ patient blast xenograft growth in zebrafish. Furthermore, OT-55 synergized with omacetaxine in imatinib-resistant KBM-5 R cells to inhibit the expression of Mcl-1, triggering apoptosis. In imatinib-resistant K562 R cells, OT-55 triggered necrosis and blocked tumor formation in zebrafish in combination with omacetaxine.",

keywords = "Calreticulin, Eukaryotic initiation factor 2α, High mobility group box 1, Phagocytosis",

author = "Aloran Mazumder and Lee, {Jin Young} and Oualid Talhi and Claudia Cerella and S{\'e}bastien Chateauvieux and Anthoula Gaigneaux and Hong, {Che Ry} and Kang, {Hyoung Jin} and Youngjo Lee and Kim, {Kyu Won} and Kim, {Dong Wook} and Shin, {Hee Young} and Mario Dicato and Khaldoun Bachari and Silva, {Artur M.S.} and Barbora Orlikova-Boyer and Marc Diederich",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier B.V.",

year = "2018",

month = dec,

day = "1",

doi = "10.1016/j.canlet.2018.07.041",

language = "English",

volume = "438",

pages = "197--218",

journal = "Cancer Letters",

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Mazumder, A, Lee, JY, Talhi, O, Cerella, C, Chateauvieux, S, Gaigneaux, A, Hong, CR, Kang, HJ, Lee, Y, Kim, KW, Kim, DW, Shin, HY, Dicato, M, Bachari, K, Silva, AMS, Orlikova-Boyer, B & Diederich, M 2018, 'Hydroxycoumarin OT-55 kills CML cells alone or in synergy with imatinib or Synribo: Involvement of ER stress and DAMP release', Cancer Letters, vol. 438, pp. 197-218. https://doi.org/10.1016/j.canlet.2018.07.041

TY - JOUR

T1 - Hydroxycoumarin OT-55 kills CML cells alone or in synergy with imatinib or Synribo

T2 - Involvement of ER stress and DAMP release

AU - Mazumder, Aloran

AU - Lee, Jin Young

AU - Talhi, Oualid

AU - Cerella, Claudia

AU - Chateauvieux, Sébastien

AU - Gaigneaux, Anthoula

AU - Hong, Che Ry

AU - Kang, Hyoung Jin

AU - Lee, Youngjo

AU - Kim, Kyu Won

AU - Kim, Dong Wook

AU - Shin, Hee Young

AU - Dicato, Mario

AU - Bachari, Khaldoun

AU - Silva, Artur M.S.

AU - Orlikova-Boyer, Barbora

AU - Diederich, Marc

PY - 2018/12/1

Y1 - 2018/12/1

N2 - We synthetized and investigated the anti-leukemic potential of the novel cytostatic bis(4-hydroxycoumarin) derivative OT-55 which complied with the Lipinski's rule of 5 and induced differential toxicity in various chronic myeloid leukemia (CML) cell models. OT-55 triggered ER stress leading to canonical, caspase-dependent apoptosis and release of danger associated molecular patterns. Consequently, OT-55 promoted phagocytosis of OT-55-treated CML cells by both murine and human monocyte-derived macrophages. Moreover, OT-55 inhibited tumor necrosis factor α-induced activation of nuclear factor-кB and produced synergistic effects when used in combination with imatinib to inhibit colony formation in vitro and Bcr-Abl+ patient blast xenograft growth in zebrafish. Furthermore, OT-55 synergized with omacetaxine in imatinib-resistant KBM-5 R cells to inhibit the expression of Mcl-1, triggering apoptosis. In imatinib-resistant K562 R cells, OT-55 triggered necrosis and blocked tumor formation in zebrafish in combination with omacetaxine.

AB - We synthetized and investigated the anti-leukemic potential of the novel cytostatic bis(4-hydroxycoumarin) derivative OT-55 which complied with the Lipinski's rule of 5 and induced differential toxicity in various chronic myeloid leukemia (CML) cell models. OT-55 triggered ER stress leading to canonical, caspase-dependent apoptosis and release of danger associated molecular patterns. Consequently, OT-55 promoted phagocytosis of OT-55-treated CML cells by both murine and human monocyte-derived macrophages. Moreover, OT-55 inhibited tumor necrosis factor α-induced activation of nuclear factor-кB and produced synergistic effects when used in combination with imatinib to inhibit colony formation in vitro and Bcr-Abl+ patient blast xenograft growth in zebrafish. Furthermore, OT-55 synergized with omacetaxine in imatinib-resistant KBM-5 R cells to inhibit the expression of Mcl-1, triggering apoptosis. In imatinib-resistant K562 R cells, OT-55 triggered necrosis and blocked tumor formation in zebrafish in combination with omacetaxine.

KW - Calreticulin

KW - Eukaryotic initiation factor 2α

KW - High mobility group box 1

KW - Phagocytosis

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U2 - 10.1016/j.canlet.2018.07.041

DO - 10.1016/j.canlet.2018.07.041

M3 - Article

C2 - 30205168

AN - SCOPUS:85053822421

SN - 0304-3835

VL - 438

SP - 197

EP - 218

JO - Cancer Letters

JF - Cancer Letters

ER -

Hydroxycoumarin OT-55 kills CML cells alone or in synergy with imatinib or Synribo: Involvement of ER stress and DAMP release

Abstract

Keywords

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