Induction of early apoptosis marker by morphine in human lung and breast carcinoma cell lines.
We have investigated whether morphine and codeine, potent analgesic compounds most commonly used as cancer pain relievers, show tumor-specific cytotoxic activity and whether they can induce apoptosis or necrosis by monitoring the stainability with Annexin V and propidium iodide with fluorescence-activated cell sorter. Both opioids showed higher cytotoxic activity against three human tumor cell lines (lung carcinoma A549, mammary gland carcinoma MCF7, promyelocytic leukemia HL-60) than against three normal human cells (periodontal ligament fibroblast HPLF, gingival fibroblast HGF, pulp cell HPC). Morphine produced the major part of the apoptotic cell populations and the minor part of the necrotic cell populations in A549 and MCF7 cells, more effectively than codeine. In addition, morphine increased the activity of mitochondrial Mn-containing superoxide dismutase (MnSOD) in HL-60 cells, but decreased the MnSOD activity in A549 and MCF7 cells. The apoptosis-inducing activity of opioids may provide new strategies for the treatment and prevention of cancer.
Hatsukari
Ikusuke
I
Department of Anesthesiology, Saitama Medical School, Department of Anesthesiology, Department of Dental Pharmacology, Meikai University School of Dentistry, Saitama, Japan.
Hitosugi
Naoko
N
Matsumoto
Isao
I
Nagasaka
Hiroshi
H
Sakagami
Hiroshi
H
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D002460:Cell Line; D003061:Codeine / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D009020:Morphine / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000701:Analgesics, Opioid; D000970:Antineoplastic Agents; D009020:Morphine; D013482:Superoxide Dismutase; D003061:Codeine