c-IAP1 is Overexpressed in HL-60 Cells Selected for Doxorubicin Resistance: Effects on Etoposide-induced Apoptosis

Susan A.J. Vaziri; Dale R. Grabowski; Masahiro Tabata; Katherine A. Holmes; Joseph Sterk; Nagio Takigawa; Ronald M. Bukowski; Mahrukh K. Ganapathi; Ram Ganapathi

c-IAP1 is Overexpressed in HL-60 Cells Selected for Doxorubicin Resistance: Effects on Etoposide-induced Apoptosis

Susan A.J. Vaziri, Dale R. Grabowski, Masahiro Tabata, Katherine A. Holmes, Joseph Sterk, Nagio Takigawa, Ronald M. Bukowski, Mahrukh K. Ganapathi, Ram Ganapathi

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

13 Citations (Scopus)

Abstract

Background: We previously demonstrated that KN-62, an inhibitor of calcium calmodulin-dependent enzymes, sensitizes human leukemia HL-60 cells resistant to topoisomerase II-targeting drugs. The objective of this study was to determine pathways of apoptosis downstream of DNA damage induced by KN-62 co-treatment with VP-16. Materials and Methods: HL-60/Y/DOX0. 05 cells were treated with VP-16, KN-62, or VP-16 +KN-62. Following treatment, cells were assayed for c-IAP1, c-IAP2 and XIAP protein expression, as well as caspase activation, cytochrome c release and PARP cleavage. Results: Baseline c-IAP1 protein levels were 2-fold higher in HL60 cells selected for resistance to doxorubicin compared to the parent sensitive line. VP-16 and KN-62 co-treatment was associated with caspase activation via the mitochondrial pathway and significant reductions (p=0.002) in c-IAP1 protein expression but not with c-IAP2 or XIAP. Conclusion: These data suggest that KN-62 co-treatment sensitizes doxorubicin-resistant cells to VP-16-induced apoptosis by enhancing caspase activity and reducing c-IAP1 expression.

Original language	English
Pages (from-to)	3657-3661
Number of pages	5
Journal	Anticancer research
Volume	23
Issue number	5 A
Publication status	Published - Sep 2003
Externally published	Yes

Keywords

Apoptosis
Etoposide
Inhibitor of calcium calmodulin-dependent enzymes
KN-62
Topoisomerase II-targeting drug resistance
c-IAP1

ASJC Scopus subject areas

Oncology
Cancer Research

Fingerprint Dive into the research topics of 'c-IAP1 is Overexpressed in HL-60 Cells Selected for Doxorubicin Resistance: Effects on Etoposide-induced Apoptosis'. Together they form a unique fingerprint.

Cite this

c-IAP1 is Overexpressed in HL-60 Cells Selected for Doxorubicin Resistance : Effects on Etoposide-induced Apoptosis. / Vaziri, Susan A.J.; Grabowski, Dale R.; Tabata, Masahiro; Holmes, Katherine A.; Sterk, Joseph; Takigawa, Nagio; Bukowski, Ronald M.; Ganapathi, Mahrukh K.; Ganapathi, Ram.

In: Anticancer research, Vol. 23, No. 5 A, 09.2003, p. 3657-3661.

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

@article{4676b342770f4fd7b984e47012eb66f1,

title = "c-IAP1 is Overexpressed in HL-60 Cells Selected for Doxorubicin Resistance: Effects on Etoposide-induced Apoptosis",

abstract = "Background: We previously demonstrated that KN-62, an inhibitor of calcium calmodulin-dependent enzymes, sensitizes human leukemia HL-60 cells resistant to topoisomerase II-targeting drugs. The objective of this study was to determine pathways of apoptosis downstream of DNA damage induced by KN-62 co-treatment with VP-16. Materials and Methods: HL-60/Y/DOX0. 05 cells were treated with VP-16, KN-62, or VP-16 +KN-62. Following treatment, cells were assayed for c-IAP1, c-IAP2 and XIAP protein expression, as well as caspase activation, cytochrome c release and PARP cleavage. Results: Baseline c-IAP1 protein levels were 2-fold higher in HL60 cells selected for resistance to doxorubicin compared to the parent sensitive line. VP-16 and KN-62 co-treatment was associated with caspase activation via the mitochondrial pathway and significant reductions (p=0.002) in c-IAP1 protein expression but not with c-IAP2 or XIAP. Conclusion: These data suggest that KN-62 co-treatment sensitizes doxorubicin-resistant cells to VP-16-induced apoptosis by enhancing caspase activity and reducing c-IAP1 expression.",

keywords = "Apoptosis, Etoposide, Inhibitor of calcium calmodulin-dependent enzymes, KN-62, Topoisomerase II-targeting drug resistance, c-IAP1",

author = "Vaziri, {Susan A.J.} and Grabowski, {Dale R.} and Masahiro Tabata and Holmes, {Katherine A.} and Joseph Sterk and Nagio Takigawa and Bukowski, {Ronald M.} and Ganapathi, {Mahrukh K.} and Ram Ganapathi",

year = "2003",

month = sep,

language = "English",

volume = "23",

pages = "3657--3661",

journal = "Anticancer Research",

issn = "0250-7005",

publisher = "International Institute of Anticancer Research",

number = "5 A",

}

TY - JOUR

T1 - c-IAP1 is Overexpressed in HL-60 Cells Selected for Doxorubicin Resistance

T2 - Effects on Etoposide-induced Apoptosis

AU - Vaziri, Susan A.J.

AU - Grabowski, Dale R.

AU - Tabata, Masahiro

AU - Holmes, Katherine A.

AU - Sterk, Joseph

AU - Takigawa, Nagio

AU - Bukowski, Ronald M.

AU - Ganapathi, Mahrukh K.

AU - Ganapathi, Ram

PY - 2003/9

Y1 - 2003/9

N2 - Background: We previously demonstrated that KN-62, an inhibitor of calcium calmodulin-dependent enzymes, sensitizes human leukemia HL-60 cells resistant to topoisomerase II-targeting drugs. The objective of this study was to determine pathways of apoptosis downstream of DNA damage induced by KN-62 co-treatment with VP-16. Materials and Methods: HL-60/Y/DOX0. 05 cells were treated with VP-16, KN-62, or VP-16 +KN-62. Following treatment, cells were assayed for c-IAP1, c-IAP2 and XIAP protein expression, as well as caspase activation, cytochrome c release and PARP cleavage. Results: Baseline c-IAP1 protein levels were 2-fold higher in HL60 cells selected for resistance to doxorubicin compared to the parent sensitive line. VP-16 and KN-62 co-treatment was associated with caspase activation via the mitochondrial pathway and significant reductions (p=0.002) in c-IAP1 protein expression but not with c-IAP2 or XIAP. Conclusion: These data suggest that KN-62 co-treatment sensitizes doxorubicin-resistant cells to VP-16-induced apoptosis by enhancing caspase activity and reducing c-IAP1 expression.

AB - Background: We previously demonstrated that KN-62, an inhibitor of calcium calmodulin-dependent enzymes, sensitizes human leukemia HL-60 cells resistant to topoisomerase II-targeting drugs. The objective of this study was to determine pathways of apoptosis downstream of DNA damage induced by KN-62 co-treatment with VP-16. Materials and Methods: HL-60/Y/DOX0. 05 cells were treated with VP-16, KN-62, or VP-16 +KN-62. Following treatment, cells were assayed for c-IAP1, c-IAP2 and XIAP protein expression, as well as caspase activation, cytochrome c release and PARP cleavage. Results: Baseline c-IAP1 protein levels were 2-fold higher in HL60 cells selected for resistance to doxorubicin compared to the parent sensitive line. VP-16 and KN-62 co-treatment was associated with caspase activation via the mitochondrial pathway and significant reductions (p=0.002) in c-IAP1 protein expression but not with c-IAP2 or XIAP. Conclusion: These data suggest that KN-62 co-treatment sensitizes doxorubicin-resistant cells to VP-16-induced apoptosis by enhancing caspase activity and reducing c-IAP1 expression.

KW - Apoptosis

KW - Etoposide

KW - Inhibitor of calcium calmodulin-dependent enzymes

KW - KN-62

KW - Topoisomerase II-targeting drug resistance

KW - c-IAP1

UR - http://www.scopus.com/inward/record.url?scp=0344442296&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344442296&partnerID=8YFLogxK

M3 - Article

C2 - 14666661

AN - SCOPUS:0344442296

VL - 23

SP - 3657

EP - 3661

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 5 A

ER -

c-IAP1 is Overexpressed in HL-60 Cells Selected for Doxorubicin Resistance: Effects on Etoposide-induced Apoptosis

Abstract

Keywords

ASJC Scopus subject areas

Other files and links

Cite this