title: In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an antimalarial drug, in a gastric cancer cell line (PG100).
abstract: Artemisinin is a sesquiterpene lactone endoperoxide, obtained from Artemisia annua, and extensively used as an antimalarial drug. Many studies have reported the genotoxic and cytotoxic effects of artemisinins; however, there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with artemether, an artemisinin derivative. Gastric cancer is the fourth most frequent type of cancer and the second highest cause of cancer mortality worldwide. Thus, the aim of this study was to evaluate the in vitro genotoxic and cytotoxic effects induced by artemether in gastric cancer cell line (PG100) and compare them with the results obtained in human lymphocytes exposed to the same conditions. We used MTT (3-(4,5-methylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide) assay, comet assay and ethidium bromide/acridine orange viability staining to evaluate the cytotoxic and genotoxic effects of artemether in PG100. MTT assay showed a decrease in the survival percentages for both cell types treated with different concentrations of artemether (P < 0.05). PG100 also showed a significant dose-dependent increase in DNA damage index at concentrations of 119.4 and 238.8 µg ml(-1) (P < 0.05). Our results showed that artemether induced necrosis in PG100 at concentrations of 238.8 and 477.6 µg ml(-1), for all the tested harvest times (P < 0.05). In lymphocytes, artemether induced both apoptosis and necrosis at concentrations of 238.8 and 477.6 µg ml(-1), for all the tested harvest times (P < 0.05). In conclusion, human lymphocytes were more sensitive to the cytotoxic effects of the antimalarial drug than the gastric cancer cell line PG100.
authors.affiliation: Human Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa, 01, CEP, 66075-110, Belém, PA, Brazil.
authors.forename: Diego Di Felipe Ávila
authors.initials: DD
authors.lastname: Alcântara
authors.forename: Helem Ferreira
authors.initials: HF
authors.lastname: Ribeiro
authors.forename: Plínio Cerqueira Dos Santos
authors.initials: PC
authors.lastname: Cardoso
authors.forename: Taíssa Maíra Thomaz
authors.initials: TM
authors.lastname: Araújo
authors.forename: Rommel Rodriguez
authors.initials: RR
authors.lastname: Burbano
authors.forename: Adriana Costa
authors.initials: AC
authors.lastname: Guimarães
authors.forename: André Salim
authors.initials: AS
authors.lastname: Khayat
authors.forename: Marcelo
authors.initials: M
authors.lastname: de Oliveira Bahia
mesh_terms: D000962:Antimalarials / Q000494:pharmacology / Q000633:toxicity; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008856:Microscopy, Fluorescence; D009153:Mutagens / Q000494:pharmacology / Q000633:toxicity; D009336:Necrosis
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D037621:Artemisinins; D009153:Mutagens; D000077549:Artemether