The combined effect of dichloroacetate and 3-bromopyruvate on glucose metabolism in colorectal cancer cell line, HT-29; the mitochondrial pathway apoptosis

BMC Cancer

Hojatolla Nikravesh¹  Soheila Alboghobeish²  Leila Zeidooni³  Mohammad Javad Khodayar⁴  Masoud Mahdavinia⁴  Ali Teimoori⁵  Babak Behmanesh⁶ 

[1] Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;Department of Toxicology, Faculty of Pharmacy, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;Department of Pharmacology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;Department of Toxicology, Faculty of Pharmacy, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;Department of Toxicology, Faculty of Pharmacy, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;Toxicology Research Center,Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;Department of Virology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;

关键词: Apoptosis;    3-Bromopyruvate;    Dichloroacetate;    Colorectal cancer cells;    5-fluorouracil;   

DOI  :  10.1186/s12885-021-08564-3

来源: Springer

【 摘 要 】

Background5-Fluorouracil (5-FU) is regarded as the first line treatment for colorectal cancer; however, its effectiveness is limited by drug resistance. The ultimate goal of cancer therapy is induction of cancer cell death to achieve an effective outcome with minimal side effects. The present work aimed to assess the anti-cancer activities of mitocans which can be considered as an effective anticancer drug due to high specificity in targeting cancer cells.MethodsMTT (3–4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) assay was performed to determine the effects of our mitocans on cell viability and cell death. Apoptosis and necrosis, caspase 3 activity, mitochondrial membrane potential and ROS production in HT29 cell lines were analyzed by ApopNexin™ FITC/PI Kit, Caspase- 3 Assay Kit, MitoTracker Green and DCFH-DA, respectively. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression level of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) genes in HT29 cell lines.ResultsTreatment with mitocans (3Br-P + DCA) inhibited the growth of HT29. Moreover, 3Br-P + DCA significantly induced apoptosis and necrosis, activation of caspase 3 activity, depolarize the mitochondrial membrane potential, and ROS production. At a molecular level, 3Br-P + DCA treatment remarkably down-regulated the expression of Bcl-2, while up-regulated the expression of Bax.ConclusionMitocans, in particular the combined drug, 3Br-P + DCA, could be regarded and more evaluated as a safe and effective compound for CRC treatment. Targeting hexokinase and pyruvate dehydrogenase kinase enzymes may be an option to overcome 5-FU -mediated chemo-resistant in colorectal cancer.

【 授权许可】

CC BY