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DNA topoisomerase 2-alpha Myeloperoxidase Teniposide Teniposide O2 NADH Teniposide catechol derivative Formaldehyde NAD H2O Teniposide catechol derivative NAD Teniposide o-quinone derivative NADH Magnesium Cytochrome P450 3A4 Cytochrome P450 3A5 Cell cycle Heme Heme Oxidative DNA Damage (Cell Death) DNA repair Calcium Heme S- DNA replication M- mitosis/ cell division G2- growth, preparation for mitosis and DNA repair Cancer Cell DNA strand break G1- cell growth Re-ligation of DNA strand breaks cannot occur since DNA toposiomerase II is non-functional. This leads to errors in DNA synthesis Nucleus Apoptosis Errors in DNA synthesis promotes apoptosis of the cancer cell Hepatocyte Liver
Mitochondria Nucleus TOP2A MPO Teniposide Teniposide Oxygen NADH Teniposide catechol derivative Formaldehyde NAD Water Teniposide catechol derivative NAD Teniposide o-quinone derivative NADH CYP3A4 CYP3A5 Oxidative DNA Damage (Cell Death)
TOP2A MPO VM-26 VM-26 O2 NADH TCD Formol NAD H2O TCD NAD TenpOQD NADH Mg2+ CYP3A4 CYP3A5 Cell cycle Heme Heme O D D C DNA repair Ca2+ Heme S- DNA replication M- mitosis/ cell division G2- growth, preparation for mitosis and DNA repair Cancer Cell DNA strand break G1- cell growth Re-ligation of DNA strand breaks cannot occur since DNA toposiomerase II is non-functional. This leads to errors in DNA synthesis Nucleus Apoptosis Errors in DNA synthesis promotes apoptosis of the cancer cell Hepatocyte Liver
Mitochondria Nucleus TOP2A MPO VM-26 VM-26 O2 NADH TCD Formol NAD H2O TCD NAD TenpOQD NADH CYP3A4 CYP3A5 O D D C