Bee Pollen and Doxorubicin by Synergistic Effects Inhibit the Proliferation of Breast Tumors in 4T1 Tumor-bearing BALB/c Mice: A Biochemical, Immunohistochemical,and Molecular Approach

Abstract

Objectives This study investigated the effects of BP and doxorubicin (DOX) on 4T1 tumor cells in a mouse model. Materials and Methods After inducing breast tumors, 70 4T1-tumor-bearing BALB/c mice were divided into seven groups ( n = 10/group). The groups were treated with DOX and BP for 35 days. On the 36th day, blood was taken from the heart, and serum was separated to measure levels of cytokines, estrogen, progesterone, testosterone, and nitric oxide. Antioxidant enzyme activities, as well as tissue ferric-reducing antioxidant power (FRAP) and malondialdehyde (MDA) levels, were evaluated. The expression of apoptotic genes and metastasis was measured using real-time polymerase chain reaction (PCR), while the expression of apoptotic proteins was evaluated using Western blotting. Finally, Ki-67 and p-53 were examined using immunohistochemistry to determine apoptosis. Results The study found that BP, with its synergistic effects with DOX, reduced the volume of tumors and increased the expression of apoptotic genes and proteins. In a dose-dependent manner, groups receiving BP and DOX with their synergistic effects reduced the level of estrogen and nitric oxide and also reduced the level of pro-inflammatory cytokines. BP along with DOX increased serum interferon-γ (IFN-γ) levels. Tumor tissue FRAP and thiobarbituric acid reactive substances (TBARS) levels increased in BP-treated groups. Ki-67 and Bcl-2 proliferation markers levels decreased, and p53 levels increased in 4T1-breast tumors. Conclusion The study concluded that BP with its synergistic effects along with DOX has the ability to suppress the growth of tumors and can also inhibit the oxidative damage of DOX.

Bee pollen as a food and feed supplement and a therapeutic remedy: recent trends in nanotechnology

“…In addition, it was noted that both BP and DOX work synergistically and upregulate the expression of apoptotic genes and proteins and eventually decrease the volume of tumor cells while decreasing the level of nitric oxide and estrogen and downregulating the level of pro-inflammatory cytokines in mice models with induced 4 T1 breast tumors. BP isoflavones have been used as anticancer agent against breast cancer cells such as triple-negative breast cancer (TNBC) and restrain the activity of endogenous estrogen ( 177 ). Research has shown that isoflavones and flavonoids of BP restrain the cell cycle at G1 and or G2/M stages and upregulate the expression of pro-apoptotic genes and dysfunction of the capability of enzymes associated with the growth and development of tumor cells while hindering the activity of intermediates such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) and also inhibiting the production of ROS ( 177 , 178 ).…”

“…BP isoflavones have been used as anticancer agent against breast cancer cells such as triple-negative breast cancer (TNBC) and restrain the activity of endogenous estrogen ( 177 ). Research has shown that isoflavones and flavonoids of BP restrain the cell cycle at G1 and or G2/M stages and upregulate the expression of pro-apoptotic genes and dysfunction of the capability of enzymes associated with the growth and development of tumor cells while hindering the activity of intermediates such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) and also inhibiting the production of ROS ( 177 , 178 ). Wang et al concluded that BP polysaccharides (extracted from Rosa rugosa ) exhibited anticancer activity in vitro against HCT116 (human colon carcinoma) and HT-29 (colon cancer) cells in a dose-dependent way ( 179 , 180 ).…”