Differential activities of thalidomide and isoprenoid biosynthetic pathway inhibitors in multiple myeloma cells

Sarah A. Holstein; Huaxiang Tong; Raymond J. Hohl

doi:10.1016/j.leukres.2009.06.035

Differential activities of thalidomide and isoprenoid biosynthetic pathway inhibitors in multiple myeloma cells

Sarah A. Holstein
, Huaxiang Tong
, Raymond J. Hohl

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

22 Scopus citations

Abstract

Thalidomide has emerged as an effective agent for treating multiple myeloma, however the precise mechanism of action remains unknown. Agents known to target the isoprenoid biosynthetic pathway (IBP) can have cytotoxic effects in myeloma cells. The interactions between thalidomide and IBP inhibitors in human multiple myeloma cells were evaluated. Enhanced cytotoxicity and induction of apoptosis were observed in RPMI-8226 cells. Examination of intracellular levels of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) revealed a wide variance in basal levels and response to IBP inhibitors. These findings provide a mechanism for the differential sensitivity of myeloma cells to pharmacologic manipulation of the IBP.

Original language	English (US)
Pages (from-to)	344-351
Number of pages	8
Journal	Leukemia Research
Volume	34
Issue number	3
DOIs	https://doi.org/10.1016/j.leukres.2009.06.035
State	Published - Mar 2010

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Hematology
Oncology
Cancer Research

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10.1016/j.leukres.2009.06.035

Cite this

@article{19c5418210df43f1ab81017cf9f893d3,

title = "Differential activities of thalidomide and isoprenoid biosynthetic pathway inhibitors in multiple myeloma cells",

abstract = "Thalidomide has emerged as an effective agent for treating multiple myeloma, however the precise mechanism of action remains unknown. Agents known to target the isoprenoid biosynthetic pathway (IBP) can have cytotoxic effects in myeloma cells. The interactions between thalidomide and IBP inhibitors in human multiple myeloma cells were evaluated. Enhanced cytotoxicity and induction of apoptosis were observed in RPMI-8226 cells. Examination of intracellular levels of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) revealed a wide variance in basal levels and response to IBP inhibitors. These findings provide a mechanism for the differential sensitivity of myeloma cells to pharmacologic manipulation of the IBP.",

author = "Holstein, \{Sarah A.\} and Huaxiang Tong and Hohl, \{Raymond J.\}",

note = "Funding Information: This project was supported by the Roy J. Carver Charitable Trust as a Research Program of Excellence and the Roland W. Holden Family Program for Experimental Cancer Therapeutics. S.A.H. was supported through a NIH T32 training grant. Funding sources did not have a role in study design, collection/analysis/interpretation of data, writing of the manuscript, or decision to submit for publication. ",

year = "2010",

month = mar,

doi = "10.1016/j.leukres.2009.06.035",

language = "English (US)",

volume = "34",

pages = "344--351",

journal = "Leukemia Research",

issn = "0145-2126",

publisher = "Elsevier Ltd",

number = "3",

}

TY - JOUR

T1 - Differential activities of thalidomide and isoprenoid biosynthetic pathway inhibitors in multiple myeloma cells

AU - Holstein, Sarah A.

AU - Tong, Huaxiang

AU - Hohl, Raymond J.

N1 - Funding Information: This project was supported by the Roy J. Carver Charitable Trust as a Research Program of Excellence and the Roland W. Holden Family Program for Experimental Cancer Therapeutics. S.A.H. was supported through a NIH T32 training grant. Funding sources did not have a role in study design, collection/analysis/interpretation of data, writing of the manuscript, or decision to submit for publication.

PY - 2010/3

Y1 - 2010/3

N2 - Thalidomide has emerged as an effective agent for treating multiple myeloma, however the precise mechanism of action remains unknown. Agents known to target the isoprenoid biosynthetic pathway (IBP) can have cytotoxic effects in myeloma cells. The interactions between thalidomide and IBP inhibitors in human multiple myeloma cells were evaluated. Enhanced cytotoxicity and induction of apoptosis were observed in RPMI-8226 cells. Examination of intracellular levels of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) revealed a wide variance in basal levels and response to IBP inhibitors. These findings provide a mechanism for the differential sensitivity of myeloma cells to pharmacologic manipulation of the IBP.

AB - Thalidomide has emerged as an effective agent for treating multiple myeloma, however the precise mechanism of action remains unknown. Agents known to target the isoprenoid biosynthetic pathway (IBP) can have cytotoxic effects in myeloma cells. The interactions between thalidomide and IBP inhibitors in human multiple myeloma cells were evaluated. Enhanced cytotoxicity and induction of apoptosis were observed in RPMI-8226 cells. Examination of intracellular levels of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) revealed a wide variance in basal levels and response to IBP inhibitors. These findings provide a mechanism for the differential sensitivity of myeloma cells to pharmacologic manipulation of the IBP.

UR - https://www.scopus.com/pages/publications/77649182629

UR - https://www.scopus.com/pages/publications/77649182629#tab=citedBy

U2 - 10.1016/j.leukres.2009.06.035

DO - 10.1016/j.leukres.2009.06.035

M3 - Article

C2 - 19646757

AN - SCOPUS:77649182629

SN - 0145-2126

VL - 34

SP - 344

EP - 351

JO - Leukemia Research

JF - Leukemia Research

IS - 3

ER -

Differential activities of thalidomide and isoprenoid biosynthetic pathway inhibitors in multiple myeloma cells

Abstract

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