Cell death-inducing activity of opiates in human oral tumor cell lines

Masami Kawase, Hiroshi Sakagami, Kenichiro Furuya, Hirotaka Kikuchi, Hirofumi Nishikawa, Noboru Motohashi, Yasunori Morimoto, Andreas Varga, J. Molnár

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

In screening cytotoxic agents in morphine alkaloids [TE1-10], codeinone [TE8] was cytotoxic against two human oral tumor cells lines (HSC-2 and HSG). The cytotoxic activity of codeinone (CC50=1.0-1.2/μg/mL) against HSC-2 or HSG cells was higher than that of doxorubicin (CC50=1.9-2.0 μg/mL). Human oral gingival fibroblasts (HGF) were relatively resistant to codeinone, as judged by higher SI ratio (3.7) suggesting the tumor-selective cytotoxicity of codeinone. The cytotoxic activity of morphine (CC50=221 μg/mL) against HSC-2 was slightly lower than that of codeine (CC50=186 μg/mL), thebaine (CC50=125 μg/mL), etorphine (CC50=94 μg/mL) or dihydroetorphine (CC50=60 μg/mL). A study of structurally-related compounds suggested that the α,β-unsaturated ketone group of codeinone was responsible for its antitumor cytotoxicity. The cytotoxic activity of codeinone was significantly reduced by N-acetylcysteine, but not affected by FeCl3, CuCl2, CoCl2, sodium ascorbate or catalase. Neither codeinone nor morphine inhibited P-glycoprotein-mediated rhodamine-123 efflux in multidrug resistant mouse T lymphoma L5178 transfected with human MDR 1 gene. These data suggest that codeinone induces cytotoxicity in oral tumor cell lines, possibly by a Michael-like addition of a protein SH or of an amino group to the bouble bond of codeinone.

Original languageEnglish
Pages (from-to)211-214
Number of pages4
JournalAnticancer Research
Volume22
Issue number1 A
Publication statusPublished - 2002

Fingerprint

Opiate Alkaloids
Tumor Cell Line
Cell Death
Morphine
Leukemia L5178
Thebaine
Etorphine
MDR Genes
Rhodamine 123
6-codeinone
Codeine
Cytotoxins
Acetylcysteine
P-Glycoprotein
Ketones
Alkaloids
Catalase
Doxorubicin
Ascorbic Acid

Keywords

  • Codeinone
  • Cytotoxic activity
  • DNA fragmentation
  • MDR reversal
  • Morphine alkaloid
  • Oral tumor cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kawase, M., Sakagami, H., Furuya, K., Kikuchi, H., Nishikawa, H., Motohashi, N., ... Molnár, J. (2002). Cell death-inducing activity of opiates in human oral tumor cell lines. Anticancer Research, 22(1 A), 211-214.

Cell death-inducing activity of opiates in human oral tumor cell lines. / Kawase, Masami; Sakagami, Hiroshi; Furuya, Kenichiro; Kikuchi, Hirotaka; Nishikawa, Hirofumi; Motohashi, Noboru; Morimoto, Yasunori; Varga, Andreas; Molnár, J.

In: Anticancer Research, Vol. 22, No. 1 A, 2002, p. 211-214.

Research output: Contribution to journalArticle

Kawase, M, Sakagami, H, Furuya, K, Kikuchi, H, Nishikawa, H, Motohashi, N, Morimoto, Y, Varga, A & Molnár, J 2002, 'Cell death-inducing activity of opiates in human oral tumor cell lines', Anticancer Research, vol. 22, no. 1 A, pp. 211-214.
Kawase M, Sakagami H, Furuya K, Kikuchi H, Nishikawa H, Motohashi N et al. Cell death-inducing activity of opiates in human oral tumor cell lines. Anticancer Research. 2002;22(1 A):211-214.
Kawase, Masami ; Sakagami, Hiroshi ; Furuya, Kenichiro ; Kikuchi, Hirotaka ; Nishikawa, Hirofumi ; Motohashi, Noboru ; Morimoto, Yasunori ; Varga, Andreas ; Molnár, J. / Cell death-inducing activity of opiates in human oral tumor cell lines. In: Anticancer Research. 2002 ; Vol. 22, No. 1 A. pp. 211-214.
@article{af1a028fc11c4cfd88ae0ae06eb348d0,
title = "Cell death-inducing activity of opiates in human oral tumor cell lines",
abstract = "In screening cytotoxic agents in morphine alkaloids [TE1-10], codeinone [TE8] was cytotoxic against two human oral tumor cells lines (HSC-2 and HSG). The cytotoxic activity of codeinone (CC50=1.0-1.2/μg/mL) against HSC-2 or HSG cells was higher than that of doxorubicin (CC50=1.9-2.0 μg/mL). Human oral gingival fibroblasts (HGF) were relatively resistant to codeinone, as judged by higher SI ratio (3.7) suggesting the tumor-selective cytotoxicity of codeinone. The cytotoxic activity of morphine (CC50=221 μg/mL) against HSC-2 was slightly lower than that of codeine (CC50=186 μg/mL), thebaine (CC50=125 μg/mL), etorphine (CC50=94 μg/mL) or dihydroetorphine (CC50=60 μg/mL). A study of structurally-related compounds suggested that the α,β-unsaturated ketone group of codeinone was responsible for its antitumor cytotoxicity. The cytotoxic activity of codeinone was significantly reduced by N-acetylcysteine, but not affected by FeCl3, CuCl2, CoCl2, sodium ascorbate or catalase. Neither codeinone nor morphine inhibited P-glycoprotein-mediated rhodamine-123 efflux in multidrug resistant mouse T lymphoma L5178 transfected with human MDR 1 gene. These data suggest that codeinone induces cytotoxicity in oral tumor cell lines, possibly by a Michael-like addition of a protein SH or of an amino group to the bouble bond of codeinone.",
keywords = "Codeinone, Cytotoxic activity, DNA fragmentation, MDR reversal, Morphine alkaloid, Oral tumor cells",
author = "Masami Kawase and Hiroshi Sakagami and Kenichiro Furuya and Hirotaka Kikuchi and Hirofumi Nishikawa and Noboru Motohashi and Yasunori Morimoto and Andreas Varga and J. Moln{\'a}r",
year = "2002",
language = "English",
volume = "22",
pages = "211--214",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "1 A",

}

TY - JOUR

T1 - Cell death-inducing activity of opiates in human oral tumor cell lines

AU - Kawase, Masami

AU - Sakagami, Hiroshi

AU - Furuya, Kenichiro

AU - Kikuchi, Hirotaka

AU - Nishikawa, Hirofumi

AU - Motohashi, Noboru

AU - Morimoto, Yasunori

AU - Varga, Andreas

AU - Molnár, J.

PY - 2002

Y1 - 2002

N2 - In screening cytotoxic agents in morphine alkaloids [TE1-10], codeinone [TE8] was cytotoxic against two human oral tumor cells lines (HSC-2 and HSG). The cytotoxic activity of codeinone (CC50=1.0-1.2/μg/mL) against HSC-2 or HSG cells was higher than that of doxorubicin (CC50=1.9-2.0 μg/mL). Human oral gingival fibroblasts (HGF) were relatively resistant to codeinone, as judged by higher SI ratio (3.7) suggesting the tumor-selective cytotoxicity of codeinone. The cytotoxic activity of morphine (CC50=221 μg/mL) against HSC-2 was slightly lower than that of codeine (CC50=186 μg/mL), thebaine (CC50=125 μg/mL), etorphine (CC50=94 μg/mL) or dihydroetorphine (CC50=60 μg/mL). A study of structurally-related compounds suggested that the α,β-unsaturated ketone group of codeinone was responsible for its antitumor cytotoxicity. The cytotoxic activity of codeinone was significantly reduced by N-acetylcysteine, but not affected by FeCl3, CuCl2, CoCl2, sodium ascorbate or catalase. Neither codeinone nor morphine inhibited P-glycoprotein-mediated rhodamine-123 efflux in multidrug resistant mouse T lymphoma L5178 transfected with human MDR 1 gene. These data suggest that codeinone induces cytotoxicity in oral tumor cell lines, possibly by a Michael-like addition of a protein SH or of an amino group to the bouble bond of codeinone.

AB - In screening cytotoxic agents in morphine alkaloids [TE1-10], codeinone [TE8] was cytotoxic against two human oral tumor cells lines (HSC-2 and HSG). The cytotoxic activity of codeinone (CC50=1.0-1.2/μg/mL) against HSC-2 or HSG cells was higher than that of doxorubicin (CC50=1.9-2.0 μg/mL). Human oral gingival fibroblasts (HGF) were relatively resistant to codeinone, as judged by higher SI ratio (3.7) suggesting the tumor-selective cytotoxicity of codeinone. The cytotoxic activity of morphine (CC50=221 μg/mL) against HSC-2 was slightly lower than that of codeine (CC50=186 μg/mL), thebaine (CC50=125 μg/mL), etorphine (CC50=94 μg/mL) or dihydroetorphine (CC50=60 μg/mL). A study of structurally-related compounds suggested that the α,β-unsaturated ketone group of codeinone was responsible for its antitumor cytotoxicity. The cytotoxic activity of codeinone was significantly reduced by N-acetylcysteine, but not affected by FeCl3, CuCl2, CoCl2, sodium ascorbate or catalase. Neither codeinone nor morphine inhibited P-glycoprotein-mediated rhodamine-123 efflux in multidrug resistant mouse T lymphoma L5178 transfected with human MDR 1 gene. These data suggest that codeinone induces cytotoxicity in oral tumor cell lines, possibly by a Michael-like addition of a protein SH or of an amino group to the bouble bond of codeinone.

KW - Codeinone

KW - Cytotoxic activity

KW - DNA fragmentation

KW - MDR reversal

KW - Morphine alkaloid

KW - Oral tumor cells

UR - http://www.scopus.com/inward/record.url?scp=0036254804&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036254804&partnerID=8YFLogxK

M3 - Article

VL - 22

SP - 211

EP - 214

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 1 A

ER -