Academic Journal

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

التفاصيل البيبلوغرافية
العنوان: The combined effect of dichloroacetate and 3-bromopyruvate on glucose metabolism in colorectal cancer cell line, HT-29; the mitochondrial pathway apoptosis
المؤلفون: Hojatolla Nikravesh, Mohammad Javad Khodayar, Babak Behmanesh, Masoud Mahdavinia, Ali Teimoori, Soheila Alboghobeish, Leila Zeidooni
المصدر: BMC Cancer, Vol 21, Iss 1, Pp 1-11 (2021)
بيانات النشر: BMC, 2021.
سنة النشر: 2021
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: Apoptosis, 3-Bromopyruvate, Dichloroacetate, Colorectal cancer cells, 5-fluorouracil, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Abstract Background 5-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. Methods MTT (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. Results Treatment 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. Conclusion Mitocans, 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1471-2407
Relation: https://doaj.org/toc/1471-2407
DOI: 10.1186/s12885-021-08564-3
URL الوصول: https://doaj.org/article/3681412f5f1a4cf89ee02ca2b9401d41
رقم الانضمام: edsdoj.3681412f5f1a4cf89ee02ca2b9401d41
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14712407
DOI:10.1186/s12885-021-08564-3