The Smac mimetic RMT5265.2HCL induces apoptosis in EBV and HTLV-I associated lymphoma cells by inhibiting XIAP and promoting the mitochondrial release of cytochrome C and Smac

Sampath Ramachandiran; Joan Cain; Albert Liao; Yanjuan He; Xiangxue Guo; Lawrence H. Boise; Haian Fu; Lee Ratner; Hanna Jean Khoury; Leon Bernal-Mizrachi

doi:10.1016/j.leukres.2011.12.024

The Smac mimetic RMT5265.2HCL induces apoptosis in EBV and HTLV-I associated lymphoma cells by inhibiting XIAP and promoting the mitochondrial release of cytochrome C and Smac

Sampath Ramachandiran, Joan Cain, Albert Liao, Yanjuan He, Xiangxue Guo, Lawrence H. Boise, Haian Fu, Lee Ratner, Hanna Jean Khoury, Leon Bernal-Mizrachi

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7 Scopus citations

Abstract

The inhibitors of apoptosis (IAP) are important regulators of apoptosis. However, little is known about the capacity of Smac mimetics (IAP inhibitor) to overcome virally associated-lymphoma's (VAL) resistance to apoptosis. Here, we explored the pro-apoptotic effect of a novel Smac mimetic, RMT5265.2HCL (RMT) in VAL cells. RMT improved the sensitivity to apoptosis in EBV- and to some extend in HTLV-1- but not in HHV-8-VAL. Furthermore, we identified that RMT promotes caspase 3 and 9 cleavage by inhibiting XIAP and inducing the mitochondrial efflux of Smac and cytochrome C. This investigation further support exploring the use of Smac inhibitors in VAL.

Original language	English
Pages (from-to)	784-790
Number of pages	7
Journal	Leukemia Research
Volume	36
Issue number	6
DOIs	https://doi.org/10.1016/j.leukres.2011.12.024
State	Published - Jun 2012

Keywords

EBV
HHV-8
HTLV-1
Lymphomas
Smac mimetics
XIAP

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10.1016/j.leukres.2011.12.024

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Ramachandiran, S., Cain, J., Liao, A., He, Y., Guo, X., Boise, L. H., Fu, H., Ratner, L., Khoury, H. J., & Bernal-Mizrachi, L. (2012). The Smac mimetic RMT5265.2HCL induces apoptosis in EBV and HTLV-I associated lymphoma cells by inhibiting XIAP and promoting the mitochondrial release of cytochrome C and Smac. Leukemia Research, 36(6), 784-790. https://doi.org/10.1016/j.leukres.2011.12.024

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title = "The Smac mimetic RMT5265.2HCL induces apoptosis in EBV and HTLV-I associated lymphoma cells by inhibiting XIAP and promoting the mitochondrial release of cytochrome C and Smac",

abstract = "The inhibitors of apoptosis (IAP) are important regulators of apoptosis. However, little is known about the capacity of Smac mimetics (IAP inhibitor) to overcome virally associated-lymphoma's (VAL) resistance to apoptosis. Here, we explored the pro-apoptotic effect of a novel Smac mimetic, RMT5265.2HCL (RMT) in VAL cells. RMT improved the sensitivity to apoptosis in EBV- and to some extend in HTLV-1- but not in HHV-8-VAL. Furthermore, we identified that RMT promotes caspase 3 and 9 cleavage by inhibiting XIAP and inducing the mitochondrial efflux of Smac and cytochrome C. This investigation further support exploring the use of Smac inhibitors in VAL.",

keywords = "EBV, HHV-8, HTLV-1, Lymphomas, Smac mimetics, XIAP",

author = "Sampath Ramachandiran and Joan Cain and Albert Liao and Yanjuan He and Xiangxue Guo and Boise, {Lawrence H.} and Haian Fu and Lee Ratner and Khoury, {Hanna Jean} and Leon Bernal-Mizrachi",

note = "Funding Information: L.H.B. received funding support from the NIH ( CA127910 and CA129968 ) and a GCCDSW, L.R. was supported by the National Institute of Health (NIH, CA94056 , CA10073 and CA63417 ) and L.B.-M. received funding from the Crissey Hematology and Medical Oncology Research Fund . ",

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doi = "10.1016/j.leukres.2011.12.024",

language = "English",

volume = "36",

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journal = "Leukemia Research",

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Ramachandiran, S, Cain, J, Liao, A, He, Y, Guo, X, Boise, LH, Fu, H, Ratner, L, Khoury, HJ & Bernal-Mizrachi, L 2012, 'The Smac mimetic RMT5265.2HCL induces apoptosis in EBV and HTLV-I associated lymphoma cells by inhibiting XIAP and promoting the mitochondrial release of cytochrome C and Smac', Leukemia Research, vol. 36, no. 6, pp. 784-790. https://doi.org/10.1016/j.leukres.2011.12.024

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T1 - The Smac mimetic RMT5265.2HCL induces apoptosis in EBV and HTLV-I associated lymphoma cells by inhibiting XIAP and promoting the mitochondrial release of cytochrome C and Smac

AU - Ramachandiran, Sampath

AU - Cain, Joan

AU - Liao, Albert

AU - He, Yanjuan

AU - Guo, Xiangxue

AU - Boise, Lawrence H.

AU - Fu, Haian

AU - Ratner, Lee

AU - Khoury, Hanna Jean

AU - Bernal-Mizrachi, Leon

N1 - Funding Information: L.H.B. received funding support from the NIH ( CA127910 and CA129968 ) and a GCCDSW, L.R. was supported by the National Institute of Health (NIH, CA94056 , CA10073 and CA63417 ) and L.B.-M. received funding from the Crissey Hematology and Medical Oncology Research Fund .

PY - 2012/6

Y1 - 2012/6

N2 - The inhibitors of apoptosis (IAP) are important regulators of apoptosis. However, little is known about the capacity of Smac mimetics (IAP inhibitor) to overcome virally associated-lymphoma's (VAL) resistance to apoptosis. Here, we explored the pro-apoptotic effect of a novel Smac mimetic, RMT5265.2HCL (RMT) in VAL cells. RMT improved the sensitivity to apoptosis in EBV- and to some extend in HTLV-1- but not in HHV-8-VAL. Furthermore, we identified that RMT promotes caspase 3 and 9 cleavage by inhibiting XIAP and inducing the mitochondrial efflux of Smac and cytochrome C. This investigation further support exploring the use of Smac inhibitors in VAL.

AB - The inhibitors of apoptosis (IAP) are important regulators of apoptosis. However, little is known about the capacity of Smac mimetics (IAP inhibitor) to overcome virally associated-lymphoma's (VAL) resistance to apoptosis. Here, we explored the pro-apoptotic effect of a novel Smac mimetic, RMT5265.2HCL (RMT) in VAL cells. RMT improved the sensitivity to apoptosis in EBV- and to some extend in HTLV-1- but not in HHV-8-VAL. Furthermore, we identified that RMT promotes caspase 3 and 9 cleavage by inhibiting XIAP and inducing the mitochondrial efflux of Smac and cytochrome C. This investigation further support exploring the use of Smac inhibitors in VAL.

KW - EBV

KW - HHV-8

KW - HTLV-1

KW - Lymphomas

KW - Smac mimetics

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SN - 0145-2126

VL - 36

SP - 784

EP - 790

JO - Leukemia Research

JF - Leukemia Research

IS - 6

ER -

The Smac mimetic RMT5265.2HCL induces apoptosis in EBV and HTLV-I associated lymphoma cells by inhibiting XIAP and promoting the mitochondrial release of cytochrome C and Smac

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