Suppression of VEGF and inflammatory cytokines, modulation of Annexin A1 and organ functions by galloylquinic acids in breast cancer model

Abstract

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.

Prevention and Co-Management of Breast Cancer-Related Osteoporosis Using Resveratrol

“…This is in line with other data demonstrating that STAT3 stimulates cytokines in BC and that it has been associated with poor prognosis [77]. Furthermore, the pro-inflammatory VEGF seems to be another important key player in the tumorigenesis of BC [78]. This is consistent with the finding that in up to 70% of BC cases, a dysregulation of cellular processes such as autophagy has been reported to be associated with a reduced expression of autophagy-promoting proteins due to aberrant DNA methylation, leading to increased therapy resistance [79,80] (Figure 3).…”

“…This is in line with other data demonstrating that STAT3 stimulates cytokines in BC and that it has been associated with poor prognosis [ 77 ]. Furthermore, the pro-inflammatory VEGF seems to be another important key player in the tumorigenesis of BC [ 78 ].…”

Koetjapic acid: unveiling its potential as a saviour in the realm of biological and medicinal properties, with a focus on anticancer mechanism of action

“…One of the important hallmarks of cancer is angiogenesis, which can be targeted as a treatment strategy for different cancers [ 36 ]. A recent study demonstrated that a naturally occurring compound galloylquinic acid suppressed the expression of VEGF and induced cytotoxicity in MCF-7 breast cancer cells [ 37 ]. Moreover, a study also revealed that galloylquinic acid along with doxorubicin, a chemotherapeutic agent, downregulated various oncogenic pathways by remarkably reducing the levels of Notch-1, VEGF, TNF-α, IL-6, cyclin D1, and NFkB, while increasing the activity of capsase-3 in tumour tissues [ 38 ].…”