Anticancer effects of crocetin in both human adenocarcinoma gastric cancer cells and rat model of gastric cancer.
This study investigated the therapeutic effect of crocetin, a carotenoid derived from saffron, on gastric adenocarcinoma (AGS) cells and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG)-induced gastric cancer in rats. An MTT assay showed a significant dose- and time-dependent inhibition of AGS cell proliferation as a result of crocetin administration. Flow cytometry and caspases activity assays revealed apoptosis had been induced in these cells; RT-PCR and Western blot analyses revealed the suppression of Bcl-2 and up-regulation of Bax expression in AGS cells treated with crocetin. These changes were not observed in normal human fibroblast (HFSF-PI3) cells. Pathological study of the tumor tissue in MNNG-induced gastric cancer in rats indicated the dose-dependent inhibition of tumor progression. In addition, crocetin reversed some changed biochemical parameters, including serum antioxidant activity and lactate dehydrogenase in rat serum. The present study demonstrates the antioxidant, anti-proliferative, and apoptotic activities of crocetin against gastric cancer that may benefit human stomach cancer treatment.
a Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
S Zahra
SZ
Bathaie
Reyhane
R
Hoshyar
Hamidreza
H
Miri
Majid
M
Sadeghizadeh
D000230:Adenocarcinoma / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002338:Carotenoids / Q000302:isolation & purification / Q000494:pharmacology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D027622:Crocus / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008769:Methylnitronitrosoguanidine; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014801:Vitamin A / Q000031:analogs & derivatives; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C487773:trans-sodium crocetinate; D014801:Vitamin A; D008769:Methylnitronitrosoguanidine; D002338:Carotenoids; D007770:L-Lactate Dehydrogenase; D020169:Caspases