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Di-2-picolylamine triggers caspase-independent apoptosis by inducing oxidative stress in human liver hepatocellular carcinoma cells.
Madide, Thobeka; Somboro, Anou M; Amoako, Daniel G; Khumalo, Hezekiel M; Khan, Rene B.
Afiliación
  • Madide T; Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban, South Africa.
  • Somboro AM; Biomedical Resource Unit, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
  • Amoako DG; Biomedical Resource Unit, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
  • Khumalo HM; Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban, South Africa.
  • Khan RB; Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban, South Africa.
Biotechnol Appl Biochem ; 68(2): 257-266, 2021 Apr.
Article en En | MEDLINE | ID: mdl-32250477
ABSTRACT
Di-2-picolylamine (DPA) is an organic compound that has been shown to possess antioxidant properties when conjugated to form a metal complex. The basis of this study was to determine the effects of DPA on the proliferation and apoptosis of human hepatocellular carcinoma cells and elucidate the possible mechanisms. The methylthiazol tetrazolium assay served to measure cell viability and generated an IC50 of 1591 µM. Luminometry was used to investigate caspase activity and ATP concentration. It was observed that the decreased cell viability was associated with reduced ATP levels. Despite increased Bax and caspase 9 activity, cell death was caspase independent as indicated by the reduction in caspase 3/7 activity. This was associated with the downregulation poly(ADP-ribose) polymerase cleavage (Western blotting). However, the Hoescht assay depicted nuclear condensation and apoptotic body formation with elevated DPA levels suggesting DNA damage in HepG2 cells. DNA damage assessed by the comet assay confirmed an increased comet tail formation. The presence of oxidative stress was investigated by quantifying reactive species (malondialdehyde and nitrates concentration) and Western blotting to confirm the expression of antioxidant proteins. The DPA increased lipid peroxidation (RNS), a marker of oxidative stress, consequently causing cell death. The accompanying upregulation of stress-associated proteins superoxide dismutase (SOD2), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and Hsp70 verifies oxidative stress.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Piperidinas / Apoptosis / Carcinoma Hepatocelular / Estrés Oxidativo / Caspasas / Neoplasias Hepáticas / Proteínas de Neoplasias Límite: Humans Idioma: En Revista: Biotechnol Appl Biochem Asunto de la revista: BIOQUIMICA / BIOTECNOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Sudáfrica

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Piperidinas / Apoptosis / Carcinoma Hepatocelular / Estrés Oxidativo / Caspasas / Neoplasias Hepáticas / Proteínas de Neoplasias Límite: Humans Idioma: En Revista: Biotechnol Appl Biochem Asunto de la revista: BIOQUIMICA / BIOTECNOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Sudáfrica