Endogenous interleukin 6 conveys resistance to cis-diamminedichloroplatinum-mediated apoptosis of the K562 human leukemic cell line.
Cisplatin is an effective chemotherapeutic agent that elicits its antineoplastic activity by binding to DNA and disrupting template functions. IL-6 is a cytokine which has been shown to play a central role in host immunological defense mechanisms. Although K562 leukemic cells have been shown to secrete IL-6, little is known of whether there exists a correlation between the expression of IL-6 and the resistance of these cells to anticancer chemotherapeutic agents. To determine the contribution of IL-6 to the regulation of cisplatin-induced apoptosis in K562 cells, we examined whether treatment of K562 cells and cisplatin-resistant K562 subclones with anti-IL-6 mAb enhances their sensitivity to cisplatin. The results show that cis-diamminedichloroplatinum (CDDP) resistance was overcome by treatment with nontoxic doses of CDDP in combination with anti-IL-6 mAb. When we tested if the synergistic effect of anti-IL-6 and cisplatin could restore the ability of K562 mutant cells to undergo apoptosis, we found the typical DNA laddering in these cells, even in the presence of a nontoxic dose of the drug. Treatment of cells with anti-IL-6 reduced the levels of glutathione. The current studies show that anti-IL-6 mAb sensitized CDDP-resistant K562 cells to CDDP by induction of apoptotic death and the reduction of glutathione levels might be implicated in the enhanced cytotoxicity observed.
Dedoussis
G V
GV
Nursing Military Academy, Vironas, Athens, 16201, Greece. dedousi@hua.gr
Mouzaki
A
A
Theodoropoulou
M
M
Menounos
P
P
Kyrtsonis
M C
MC
Karameris
A
A
Maniatis
A
A
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D002999:Clone Cells; D019008:Drug Resistance, Neoplasm / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D020014:K562 Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D015850:Interleukin-6; D002945:Cisplatin