Table 2.
Biological effects of platinum derivatives on normal cells
| Activity | Mechanism | Cell type | Drug |
|---|---|---|---|
| Catabolic metabolism | Increased consumption of glucose and generation of lactic acid | Fibroblasts | CIS; CAR |
| Induction of autophagy | Tubular epithelial cells | CIS | |
| Drug resistance | Increased expression of anti-apoptotic proteins in cancer cells related to increased production of IL-11 by fibroblasts | Skin fibroblasts | CIS |
| Accumulation of drugs in normal cells instead of cancer cells | Skin fibroblasts | CIS | |
| Induction of cellular senescence | Up-regulation of cell cycle inhibitors; deterioration of cell–cell communication; Induction of SA-β-Gal | Skin fibroblasts | CIS; CAR |
| Induction of pro-inflammatory phenotype | Activation of NF-κB-dependent inflammatory response | Proximal tubule epithelial cells | CIS |
| Overproduction of IL-1 and IL-6 | Umbilical vein endothelial cells | CIS; CAR | |
| Overproduction of ICAM-1 and IL-8 | Retinal endothelial cells | CAR | |
| Overproduction of ICAM-1 and ELAM-1 | Dermal endothelial cells | CAR | |
| Induction of cell death | Dysfunction of mitochondria; activation of caspases | Renal epithelial cells; endothelial cells | CIS |
| Induction of oxidative stress | Increased production of ROS; decreased activity of antioxidants; deregulation of mitochondrial metabolism | Renal proximal tubule epithelial cells | CIS |
| Increased DNA damage | Hippocampal neurons | CIS | |
| Increased DNA damage | Fibroblasts; Schwann cells | CAR | |
| Modulation of angiogenesis | Impaired MMP-2-related reactions of vascular endothelium | Endothelial cells | CIS |
| Increased production of VEGF | Endothelial cells | CAR |
Detailed description of effects summarized in this table is provided in the text
CIS cisplatin, CAR carboplatin