title: L-Methionine inhibits growth of human pancreatic cancer cells.
abstract: We have previously shown that L-methionine inhibits proliferation of breast, prostate, and colon cancer cells. This study extends these findings to BXPC-3 (mutated p53) and HPAC (wild-type p53) pancreatic cancer cells and explores the reversibility of these effects. Cells were exposed to L-methionine (5 mg/ml) for 7 days or for 3 days, followed by 4 days of culture without L-methionine (recovery). Cell proliferation, apoptosis, and cell cycle effects were assessed by flow cytometry after staining for Ki-67 or annexin V/propidium iodide. Cell proliferation was reduced by 31-35% after 7 days of methionine exposure; the effect persisted in BXPC-3 and HPAC cells after 4 days of recovery. Methionine increased apoptosis by 40-75% in HPAC cells, but not in BXPC-3 cells. Continuous exposure to methionine caused accumulation of BXPC-3 cells in the S phase and HPAC cells in both the G0/G1 and S phases; however, after 4 days of recovery, these effects disappeared. In conclusion, L-methionine inhibits proliferation and interferes with the cell cycle of BXPC-3 and HPAC pancreatic cancer cells; the effects on apoptosis remarkably persisted after methionine withdrawal. Apoptosis was induced only in BXPC-3 cells. Some of the differences in the effects of methionine between cell lines may be related to disparate p53 status. These findings warrant further studies on the potential therapeutic benefit of L-methionine against pancreatic cancer.
authors.affiliation: Departments of aSurgery bPharmacology, University of Sao Paulo-Ribeirão Preto, São Paulo, Brazil cDepartment of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois Departments of dSurgery ePathology, College of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Maximo A
authors.initials: MA
authors.lastname: Benavides
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Bosland
authors.forename: Cássio P
authors.initials: CP
authors.lastname: da Silva
authors.forename: Claudia T
authors.initials: CT
authors.lastname: Gomes Sares
authors.forename: Alana M Cerqueira
authors.initials: AM
authors.lastname: de Oliveira
authors.forename: Rafael
authors.initials: R
authors.lastname: Kemp
authors.forename: Rodolfo B
authors.initials: RB
authors.lastname: dos Reis
authors.forename: Vilma R
authors.initials: VR
authors.lastname: Martins
authors.forename: Suely V
authors.initials: SV
authors.lastname: Sampaio
authors.forename: Kirby I
authors.initials: KI
authors.lastname: Bland
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.forename: José S
authors.initials: JS
authors.lastname: dos Santos
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008715:Methionine / Q000494:pharmacology*; D010190:Pancreatic Neoplasms; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D008715:Methionine