Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells.

Ergul M., Bakar-Ates F.

Toxicology in vitro : an international journal published in association with BIBRA, cilt.73, ss.105138, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 73
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.tiv.2021.105138
  • Dergi Adı: Toxicology in vitro : an international journal published in association with BIBRA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.105138
  • Anahtar Kelimeler: Colchicine, Prostate cancer, Apoptosis, Cell cycle, ELISA, MMP-9, APOPTOSIS, DERIVATIVES, AUTOPHAGY
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

This work examined the cytotoxic effects of colchicine on PC3 cells and elucidated the possible underlying mechanisms of its cytotoxicity. The cells were exposed to colchicine at different concentrations ranging from 1 to 100 ng/mL for 24 h, and it showed considerable cytotoxicity with an IC50 value of 22.99 ng/mL. Mechanistic studies also exhibited that colchicine treatment results in cell cycle arrest at the G2/M phase as well as decreased mitochondrial membrane potential and increased early and late apoptotic cells. The apoptotic and DNAdamaging effects of colchicine have also been verified by fluorescence imaging and ELISA experiments, and they revealed that while colchicine treatment significantly modulated expression as increases in Bax, cleaved caspase 3, cleaved PARP, and 8-hydroxy-desoxyguanosine levels and as a decrease of BCL-2 protein expression. Besides, colchicine treatment significantly increased the total oxidant (TOS) level, which is a signal of oxidative stress and potential cause of DNA damage. Finally, the results of quantitative real-time PCR experiments demonstrated that colchicine treatment concentration-dependently suppressed MMP-9 mRNA expression. Overall, colchicine provides meaningful cytotoxicity on PC3 cells due to induced oxidative stress, reduced mitochondrial membrane potential, increased DNA damage, and finally increased apoptosis in PC3 cells. Nevertheless, further research needs to be conducted to assess the potential of colchicine as an anticancer drug for the treatment of prostate cancer.