Interaction of dacarbazine and imexon, In Vitro and In Vivo, in human A375 melanoma cells

Betty K. Samulitis, Robert T Dorr, Hsiao-Hui Chow

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Aim: We evaluated mechanisms of interaction between the alkyating agent dacarbazine (DTIC) and the prooxidant, imexon, in the human A375 melanoma cell line. Materials and Methods: The effect of DTIC and imexon, alone and in combination, was evaluated for growth inhibition (MTT), radiolabeled drug uptake, cellular thiol content (HPLC), and DNA strand breaks (Comet assay). Pharmacokinetic and antitumor effects were evaluated in mice. Results: Growth inhibition in vitro was additive with the two drugs. There was no effect on drug uptake or on the number of DNA strand breaks. There was a >75% reduction in cellular glutathione and cysteine with imexon but not DTIC. Co-administration of the two drugs in mice caused an increase in the area under the curve of both drugs, but the combination was not effective in reducing human A375 melanoma tumors in vivo. Conclusion: Imexon and dacarbazine show additive effects in vitro but not in vivo in human A375 melanoma cells.

Original languageEnglish (US)
Pages (from-to)2781-2785
Number of pages5
JournalAnticancer Research
Volume31
Issue number9
StatePublished - Sep 2011

Fingerprint

Dacarbazine
Melanoma
DNA Breaks
Pharmaceutical Preparations
Comet Assay
Drug Combinations
Growth
Sulfhydryl Compounds
Area Under Curve
Glutathione
Cysteine
Pharmacokinetics
High Pressure Liquid Chromatography
In Vitro Techniques
4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one
Cell Line
Neoplasms

Keywords

  • Additivity
  • Dacarbazine
  • Drug combinations
  • Imexon
  • Melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Interaction of dacarbazine and imexon, In Vitro and In Vivo, in human A375 melanoma cells. / Samulitis, Betty K.; Dorr, Robert T; Chow, Hsiao-Hui.

In: Anticancer Research, Vol. 31, No. 9, 09.2011, p. 2781-2785.

Research output: Contribution to journalArticle

@article{73fb0673ac604b97a3ecfe7182450d1d,
title = "Interaction of dacarbazine and imexon, In Vitro and In Vivo, in human A375 melanoma cells",
abstract = "Aim: We evaluated mechanisms of interaction between the alkyating agent dacarbazine (DTIC) and the prooxidant, imexon, in the human A375 melanoma cell line. Materials and Methods: The effect of DTIC and imexon, alone and in combination, was evaluated for growth inhibition (MTT), radiolabeled drug uptake, cellular thiol content (HPLC), and DNA strand breaks (Comet assay). Pharmacokinetic and antitumor effects were evaluated in mice. Results: Growth inhibition in vitro was additive with the two drugs. There was no effect on drug uptake or on the number of DNA strand breaks. There was a >75{\%} reduction in cellular glutathione and cysteine with imexon but not DTIC. Co-administration of the two drugs in mice caused an increase in the area under the curve of both drugs, but the combination was not effective in reducing human A375 melanoma tumors in vivo. Conclusion: Imexon and dacarbazine show additive effects in vitro but not in vivo in human A375 melanoma cells.",
keywords = "Additivity, Dacarbazine, Drug combinations, Imexon, Melanoma",
author = "Samulitis, {Betty K.} and Dorr, {Robert T} and Hsiao-Hui Chow",
year = "2011",
month = "9",
language = "English (US)",
volume = "31",
pages = "2781--2785",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "9",

}

TY - JOUR

T1 - Interaction of dacarbazine and imexon, In Vitro and In Vivo, in human A375 melanoma cells

AU - Samulitis, Betty K.

AU - Dorr, Robert T

AU - Chow, Hsiao-Hui

PY - 2011/9

Y1 - 2011/9

N2 - Aim: We evaluated mechanisms of interaction between the alkyating agent dacarbazine (DTIC) and the prooxidant, imexon, in the human A375 melanoma cell line. Materials and Methods: The effect of DTIC and imexon, alone and in combination, was evaluated for growth inhibition (MTT), radiolabeled drug uptake, cellular thiol content (HPLC), and DNA strand breaks (Comet assay). Pharmacokinetic and antitumor effects were evaluated in mice. Results: Growth inhibition in vitro was additive with the two drugs. There was no effect on drug uptake or on the number of DNA strand breaks. There was a >75% reduction in cellular glutathione and cysteine with imexon but not DTIC. Co-administration of the two drugs in mice caused an increase in the area under the curve of both drugs, but the combination was not effective in reducing human A375 melanoma tumors in vivo. Conclusion: Imexon and dacarbazine show additive effects in vitro but not in vivo in human A375 melanoma cells.

AB - Aim: We evaluated mechanisms of interaction between the alkyating agent dacarbazine (DTIC) and the prooxidant, imexon, in the human A375 melanoma cell line. Materials and Methods: The effect of DTIC and imexon, alone and in combination, was evaluated for growth inhibition (MTT), radiolabeled drug uptake, cellular thiol content (HPLC), and DNA strand breaks (Comet assay). Pharmacokinetic and antitumor effects were evaluated in mice. Results: Growth inhibition in vitro was additive with the two drugs. There was no effect on drug uptake or on the number of DNA strand breaks. There was a >75% reduction in cellular glutathione and cysteine with imexon but not DTIC. Co-administration of the two drugs in mice caused an increase in the area under the curve of both drugs, but the combination was not effective in reducing human A375 melanoma tumors in vivo. Conclusion: Imexon and dacarbazine show additive effects in vitro but not in vivo in human A375 melanoma cells.

KW - Additivity

KW - Dacarbazine

KW - Drug combinations

KW - Imexon

KW - Melanoma

UR - http://www.scopus.com/inward/record.url?scp=80051639451&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051639451&partnerID=8YFLogxK

M3 - Article

C2 - 21868520

AN - SCOPUS:80051639451

VL - 31

SP - 2781

EP - 2785

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 9

ER -