Naproxen, sulindac and salicylate, three NSAIDs (nonsteroidal anti-inflammatory drugs), were cytotoxic to human colorectal cancer cells in culture. Toxicity was accompanied by significant depletion of intracellular polyamine content. Inhibition of ornithine decarboxylase (the first enzyme of the polyamine biosynthetic pathway), induction of polyamine oxidase and spermidine/spermine N'-acetyltransferase (the enzymes responsible for polyamine catabolism) and induction of polyamine export all contributed to the decreased intracellular polyamine content. Morphological examination of the cells showed typical signs of apophosis, and this was confirmed by DNA fragmentation and measurement of caspase-3-like activity. Re-addition of spermidine to the cells partially prevented apoptosis and recovered the cell number. Thus polyamines appear to be an integral part of the signalling pathway mediating NSAID toxicity in human colorectal cancer cells, and may therefore also be important in cancer chemoprevention in humans.
机构:
Dongguk Univ, Dept Internal Med, Ilsan Hosp, Coll Med, Goyang, South KoreaGachon Univ Med & Sci, Dept Gastroenterol, Lab Translat Med, Lee Gil Ya Canc & Diabet Inst, Inchon 406840, South Korea
Lim, Yun Jeong
Lee, Jeong Sang
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机构:Gachon Univ Med & Sci, Dept Gastroenterol, Lab Translat Med, Lee Gil Ya Canc & Diabet Inst, Inchon 406840, South Korea
Lee, Jeong Sang
Ku, Yang Suh
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机构:Gachon Univ Med & Sci, Dept Gastroenterol, Lab Translat Med, Lee Gil Ya Canc & Diabet Inst, Inchon 406840, South Korea
Ku, Yang Suh
Hahm, Ki-Baik
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Gachon Univ Med & Sci, Dept Gastroenterol, Lab Translat Med, Lee Gil Ya Canc & Diabet Inst, Inchon 406840, South KoreaGachon Univ Med & Sci, Dept Gastroenterol, Lab Translat Med, Lee Gil Ya Canc & Diabet Inst, Inchon 406840, South Korea
机构:
Univ Michigan, Alfred Taubman Hlth Care Ctr, Sch Med, Dept Internal Med,Div Gastroenterol, Ann Arbor, MI 48109 USAUniv Michigan, Alfred Taubman Hlth Care Ctr, Sch Med, Dept Internal Med,Div Gastroenterol, Ann Arbor, MI 48109 USA
机构:
Pathology Department, Transplant Research Center, Shiraz University of Medical Sciences, ShirazPathology Department, Transplant Research Center, Shiraz University of Medical Sciences, Shiraz
Geramizadeh B.
Taghavi A.
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Pathology Department, Transplant Research Center, Shiraz University of Medical Sciences, ShirazPathology Department, Transplant Research Center, Shiraz University of Medical Sciences, Shiraz
Taghavi A.
Banan B.
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机构:
Pathology Department, Transplant Research Center, Shiraz University of Medical Sciences, ShirazPathology Department, Transplant Research Center, Shiraz University of Medical Sciences, Shiraz
机构:
Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Sung, JJY
Russell, RI
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Russell, RI
Yeomans, N
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Yeomans, N
Chan, FKL
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Chan, FKL
Chen, SL
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Chen, SL
Fock, KM
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Fock, KM
Goh, KL
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Goh, KL
Kullavanijaya, P
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Kullavanijaya, P
Kimura, K
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Kimura, K
Lau, CS
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Lau, CS
Louw, J
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Louw, J
Sollano, J
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机构:
Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Sollano, J
Triadiafalopulos, G
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机构:
Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Triadiafalopulos, G
Xiao, SD
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China
Xiao, SD
Brooks, P
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Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R ChinaChinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Div Gastroenterol, Shatin, Hong Kong, Peoples R China