Donkey milk kefir induces apoptosis and suppresses proliferation of Ehrlich ascites carcinoma by decreasing iNOS in mice

Abstract

Donkey milk and donkey milk kefir exhibit antiproliferative, antimutagenic and antibacterial effects. We investigated the effects of donkey milk and donkey milk kefir on oxidative stress, apoptosis and proliferation in Ehrlich ascites carcinoma (EAC) in mice. Thirty-four adult male Swiss albino mice were divided into four groups as follows: group 1, administered 0.5 ml water; group 2, administered 0.5 ml water + EAC cells; group 3, administered 0.5 ml donkey milk + EAC cells; group 4, administered 0.5 ml donkey milk kefir + EAC cells. We introduced 2.5 x 10 EAC cells into each animal by subcutaneous injection. Tap water, donkey milk and donkey milk kefir were administered by gavage for 10 days. Animals were sacrificed on day 11. After measuring the short and long diameters of the tumors, tissues were processed for histology. To determine oxidative stress, cell death and proliferation iNOS and eNOS, active caspase-3 and proliferating cell nuclear antigen were assessed using immunohistochemistry. A TUNEL assay also was used to detect apoptosis. Tumor volume decreased in the donkey milk kefir group compared to the control and donkey milk groups. Tumor volume increased in the donkey milk group compared to the control group. Proliferating cell nuclear antigen levels were higher in the donkey milk kefir group compared to the control and donkey milk groups. The number of apoptotic cells was less in the donkey milk group, compared to the control, whereas it was highest in the donkey milk kefir group. Donkey milk administration increased eNOS levels and decreased iNOS levels, compared to the control group. In the donkey milk kefir group, iNOS levels were significantly lower than those of the control and donkey milk groups, while eNOS levels were similar to the control group. Donkey milk kefir induced apoptosis, suppressed proliferation and decreased co-expression of iNOS and eNOS. Donkey milk promoted development of the tumors. Therefore, donkey milk kefir appears to be more beneficial for treating breast cancer than donkey milk.

Combination of Detoxified Pneumolysin Derivative ΔA146Ply and Berbamine as a Treatment Approach for Breast Cancer

“…Therapies targeting proliferation and apoptosis simultaneously may contribute to better tumor control. 38 , 39 , 40 This assumption is also supported by the study of Rahmani et al., 41 where they proved cotargeting BCL-2 and phosphatidylinositol 3-kinase (PI3K) used for acute myelogenous leukemia (AML) treatment.…”

The Many Faces of Kefir Fermented Dairy Products: Quality Characteristics, Flavour Chemistry, Nutritional Value, Health Benefits, and Safety

“…Usage of a mixture of 6 LAB from Japanese homemade kefir proved to be efficacious against HCT116, K562, and human natural killer KHYG-1 [84]. Donkey milk-based kefir administered at a dose of 0.5 mL/day reduced the tumour size of solid Ehrlich ascites carcinoma in a mouse model via its anti-proliferative action by regulating iNOS, eNOS and apoptosis induction [85]. Kefir's cancer cell inhibition mechanism is suggested to be via cell cycle arrest and the induction of apoptosis through upregulating BAX and downregulating BCL2 genes [86].…”

Current Knowledge on Functionality and Potential Therapeutic Uses of Donkey Milk

“…According to Esener et al [ 68 ], the release of NO could mediate the DM tumoricidal activity. NO release by PBMCs after DM exposure was also observed by Tafaro et al [ 45 ].…”

“…On the other hand, NO is a potential oncogenic molecule that promotes neovascularization and reduces blood flow in tumor tissues. Moreover, high concentrations of NO can directly cause DNA damage [ 68 , 70 ].…”