Suppression of VEGF and inflammatory cytokines, modulation of Annexin A1 and organ functions by galloylquinic acids in breast cancer model.
Mohamed A Abd El-SalamGhada El-TanboulyJairo BastosHeba A MetwalyPublished in: Scientific reports (2023)
The ongoing development of novel drugs for breast cancer aims to improve therapeutic outcomes, reduce toxicities, and mitigate resistance to chemotherapeutic agents. Doxorubicin (Dox) is known for its significant side effects caused by non-specific cytotoxicity. In this study, we investigated the antitumor activity of galloylquinic acids (BF) and the beneficial role of their combination with Dox in an Ehrlich ascites carcinoma (EAC)-bearing mouse model, as well as their cytotoxic effect on MCF-7 cells. The EAC-mice were randomized into five experimental groups: normal saline, Dox (2 mg/kg, i.p), BF (150 mg/kg, orally), Dox and BF combined mixture, and a control group. Mice were subjected to a 14-day treatment regimen. Results showed that BF compounds exerted chemopreventive effects in EAC mice group by increasing mean survival time, decreasing tumor volume, inhibiting ascites tumor cell count, modulating body weight changes, and preventing multi-organ histopathological alterations. BF suppressed the increased levels of inflammatory mediators (IL-6 and TNF-α) and the angiogenic marker VEGF in the ascitic fluid. In addition, BF and their combination with Dox exhibited significant cytotoxic activity on MCF-7 cells by inhibiting cell viability and modulating Annexin A1 level. Moreover, BF treatments could revert oxidative stress, restore liver and kidney functions, and normalize blood cell counts.
Keyphrases
- induced apoptosis
- signaling pathway
- oxidative stress
- body weight
- mouse model
- high fat diet induced
- single cell
- cell cycle arrest
- vascular endothelial growth factor
- endothelial cells
- cell therapy
- endoplasmic reticulum stress
- rheumatoid arthritis
- type diabetes
- randomized controlled trial
- peripheral blood
- stem cells
- ischemia reperfusion injury
- cell proliferation
- open label
- adipose tissue
- pi k akt
- replacement therapy