Gamma Radiation-Attenuated Toxoplasma gondii Provokes Apoptosis in Ehrlich Ascites Carcinoma-Bearing Mice Generating Long-Lasting Immunity

Abstract

Purpose: Pathological angiogenesis and apoptosis evasions are common hallmarks of cancer. A different approach to the antitumor effect of parasitic diseases caused by certain protozoans and helminthes had been adopted in recent years as they can affect many cancer characteristics. The present work is an attempt to assess the effect of gamma radiation-attenuated Toxoplasma gondii ME49 as an antiapoptotic and angiogenic regulator modifier on tumor growth aimed at improving cancer protective protocols. Methods: Attenuated Toxoplasma gondii ME49 was administered orally to mice 2 weeks before inoculation with Ehrlich ascites carcinoma to allow stimulation of the immune response. Hepatic histopathology and immune responses were determined for each group. Results: Marked suppression of the tumor proliferation with induction of long-lasting immunity by stimulating interferon γ and downregulating transforming growth factor β. The level of tumor promoting inflammatory markers (STAT-3 and tumor necrosis factor α), the angiogenic factors (vascular endothelial growth factor A, integrin, and matrix metallopeptidase 2 and matrix metallopeptidase 9), as well as nitric oxide concentration were significantly decreased. This was collimated with an improvement in apoptotic regulators (cytochrome-c, Bax, Bak, and caspase 3) in liver tissues of vaccinated mice group compared to Ehrlich ascites carcinoma-bearing one. Moreover, the histopathological investigations confirmed this improvement. Conclusion: Hence, there is an evidence of potency of radiation attenuated Toxoplasma vaccine in immune activation and targeting tumor cell that can be used as a prophylactic or an adjuvant in combination with chemotherapeutic drugs.

The roles and mechanisms of hypoxia in liver fibrosis

“…Due to the substantial proliferation of connective tissue, the oxygen supply is insufficient. When the tumor’s oxygen supply is insufficient to meet the needs of tumor cells, it is necessary to increase the oxygen supply through neovascularization or angiogenesis [ 44 ]. The highly dense blood vessels also increase the probability of tumor metastasis [ 45 ].…”

Radiosensitizing Effect of Bromelain Using Tumor Mice Model via Ki-67 and PARP-1 Inhibition

“… 34 To count the EAC cells before i.p injection, the bright line hemocytometer was used and trypan blue was added to count the viable cell under microscope. 35 The solid tumor was obtained by the intramuscular inoculation of 0.2 ml of 1 × 10 6 viable EAC cells in the right lower limb of each mouse. 36 Mice with a palpable solid tumor diameter (10 mm³) that was maintained within 7 to 10 days after inoculation were used for the study.…”

In vivo biological evaluation of sodium salt of ethyl (E)‐2‐cyano‐3‐(7‐hydroxy‐4‐methyl‐2‐oxoquinoline‐1(2H)‐yl)‐3‐(4‐hydroxyphenyl) acrylate as anticancer agent

“…31 Our results showed that the average value of the activity of caspase 3 in the liver was 30. In addition, Hafez et al 32 found that EAC-inoculated mice had significantly lower levels of the apoptotic molecule caspase 3 than the control group. Tumour formation and proliferation are caused by the breakdown of apoptotic and angiogenic regulators.…”

“…Neovascularization increases the tumour's ability to grow, invasiveness and metastatic potential. 32 Most antineoplastic chemotherapies rely on the stimulation of intrinsic apoptotic mechanisms mediated by mitochondria to kill cancer cells.…”