الفهرس | Only 14 pages are availabe for public view |
Abstract Paclitaxel is a widely used chemotherapeutic agent for a variety of cancers. Paclitaxel causes disruptingof normal microtubule dynamics by aberrant tubulin polymerization, which is crucial for cell division leading to cell cycle arrest during the mitotic phase. Although paclitaxel kills cancer cells, it causes numerous toxic side effects in the host. For that, ascorbic acid (vitamin C, ascorbate) could be an important antioxidant supplement, however, its antitumor effects are still debated. Purpose: This study aimed to examine the therapeutic effectiveness and toxicity of the combined administration of paclitaxel (PTX) with ascorbic acid (AA) in treating Ehrlich solid carcinoma (ESC)-bearing mice Methods: Fifty female Swiss albino mice were divided into five groups (ten/ each) as follows: negative control, untreated ESC control group; ESC+AA group; received daily IP ascorbic acid (300 mg/kg) daily, ESC+PTX group; received IP paclitaxel (8 mg/kg) once per week and ESC+PTX+AA group; received IP paclitaxel (8 mg/kg) once per week and ascorbic acid (300 mg/kg) daily. tumor, muscle, and liver issues from different groups were taken for subsequent analyses. Results: Tumor weight was significantly inhibited by combined treatment of PTX+AA compared to untreated tumor. This inhibition was accompanied with curbed the tumor cells as an evident of necrosis with few intact. Limitation of metastasis in liver tissue was noticed in ESC+AA and ESC+PTX+AA groups compared to the untreated ESC group. Significant decrease in Bcl2 mRNA and protein expression and increase in Trp53 mRNA and protein expression were detected in ESC of combined treated group compare to untreated ESC group. Moreover, significant increase in GSH and decrease in MDA levels in liver of combined treated group compares to untreated ESC group. Conclusions: Findings indicate the protective role of ascorbic acid against PTX-induced tissue toxicities by scavenging reactive oxygen species (ROS), so reducing oxidative stress in the host tissues. Furthermore, combined treatment of paclitaxel, ascorbic acid enhances the apoptosis of cancer cells. Ascorbic acid could have an appealing clinical approach for cancer therapy to reduce the adverse effects of chemotherapy on healthy tissues. |