Combined effects of anticancer drugs and new synthetic α-methylene-δ-lactones on MCF-7 cells.
The search for novel drug candidates is a priority goal for cancer therapy. Natural products isolated from plants are often used as valuable leads for the synthesis of analogs with simpler structure. Two synthetic α-methylene-δ-lactones with chroman-2-one skeleton, designated DL-3 and DL-5, exhibiting strong cytotoxic activity against several cancer cell lines, have been tested alone and in combination with well-known anticancer drugs, 5-fluorouracil, oxaliplatin, and taxol, in breast cancer MCF-7 cells. Parthenolide, a plant-derived α-methylene-γ-lactone, was used as a positive control. The effects on cell proliferation, DNA damage, and apoptosis induction were evaluated. Neither of the tested compounds significantly enhanced the effects produced by taxol, but a strong synergistic effect was observed with 5-fluorouracil and oxaliplatin. Only small differences between the actions of both α-methylene-δ-lactones were found. The synergistic effects produced by these compounds in MCF-7 cells were stronger as compared with parthenolide. Our findings show that simple and easy-to-obtain synthetic compounds with α-methylene-δ-lactone motif can potentiate the efficiency of anticancer drugs.
Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
Katarzyna
K
Gach
Jacek
J
Szymański
Dorota
D
Pomorska
Angelika
A
Długosz
Jakub
J
Modranka
Tomasz
T
Janecki
Anna
A
Janecka
D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007783:Lactones / Q000008:administration & dosage* / Q000138:chemical synthesis; D061986:MCF-7 Cells / Q000187:drug effects*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000008:administration & dosage
D007783:Lactones; D009944:Organoplatinum Compounds; C416683:methylene-lactone; D000077150:Oxaliplatin; D017239:Paclitaxel; D005472:Fluorouracil