Abstract
Objective:The present work was designed to study the effect of new conjugated caffeic and folic acid with silver nanoparticles with definite molecular size applied with and without gamma radiation exposure, as an antitumor agent against experimentally induced Ehrlich tumor and attempted to identify their potential molecular mechanisms of action throughout determination of anti-tumor activities using MTT cytotoxic assay against two human carcinoma cell lines in vitro, such as apoptosis analysis by flow cytometry through caspase-8, caspase-3 and TNF determination in vivo. Materials and Methods:Adult female albino mice were used and divided into five groups. Animals were sacrificed and the following parameters were estimated, glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) in blood in addition to caspase8, caspase 3 and tumor necrosis factor (TNF) of tumor tissue, liver and kidney function also measured in plasma. The tumor specimens were processed for histopathological examination. Results:Nano-silver folate caffeic (NSFC) complex compound treatment resulted in growth inhibition in Ehrlich solid tumor, Hep-G2, and MCF-7 cells (IC50 0.062 mg, 7.70 µM, and 14.50 µM, respectively). Flow cytometric analysis revealed that (NSFC) with radiation IR had apoptotic effects at caspases 8 (Mean±SD) (49.4±14), caspase3 (39.97±9.75), and TNF (40.1±3.4) more than any other groups. Those disturbances were found to be associated with a kinetic induction of apoptosis and showed modulation of the antioxidant system {glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) which were 60.70±0.80, 26.73±0.80, 39.52±0.58 respectively}at the group which took (NSFC+IR), besides its high percentage of necrotic cells by histopathological studies. In conclusion,the present study showed that the treatment of (NSFC) exhibits very efficient oncolytic activity in delaying tumor growth in mice bearing Ehrlich Solid Carcinoma (ESC) and the mechanisms underlying the inhibitory effect of the present compound involve both an apoptotic effect against Hep-G2 and MCF-7 cells and modulation of antioxidant system.
Highlights
Cancer is a group of diseases that spread quickly by the uncontrolled growth of abnormal cells and lead to death (Small Jr et al, 2017)
The present study showed that the treatment of (NSFC) exhibits very efficient oncolytic activity in delaying tumor growth in mice bearing Ehrlich Solid Carcinoma (ESC) and the mechanisms underlying the inhibitory effect of the present compound involve both an apoptotic effect against Hep-G2 and MCF-7 cells and modulation of antioxidant system
The animals were divided into five experimental groups (15 mice each) as follows: group (1) untreated control group, group (2) mice bearing Ehrlich solid carcinoma (ESC) ((2.5*106) viable Ehrlich Ascites Carcinoma (EAC) cells in 1ml saline and mouse was injected in right thigh of the lower limb by 0.1 ml ), group (3) mice bearing ESC exposed to ionizing radiation as fractionated doses (2Gy / week for 3 weeks), group (4) mice bearing ESC treated with
Summary
Cancer is a group of diseases that spread quickly by the uncontrolled growth of abnormal cells and lead to death (Small Jr et al, 2017). The propagation of cancer is continuing to increase, efforts to relieve risk factors in recent decades. Chemotherapy and radiotherapy are known for worthy adverse effects, kill only tumor cell but they discovered, they kill both tumor and health cells (Navya et al, 2019). Many side effects develop as a result of indefinite targeting anticancer factors and destitute drug delivery of those factors cannot adapt the appropriate outcome in most cases. Various methods are applied for cancer treatment, each of which has some side effects and critical restrictions. The uncontrolled propagation of cancer cells where apoptosis has greatly voided. Feel necessity for very complicated means of treatment (Jabir et al, 2016)
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