Rosmarinic acid suppresses inflammation, angiogenesis, and improves paclitaxel induced apoptosis in a breast cancer model via NF3 κB-p53-caspase-3 pathways modulation

Abstract

Rosmarinic acid is a natural polyphenolic compound that is found in different plant species and used for different medicinal purposes. This study aimed to investigate the chemo-preventive effect of rosmarinic acid and evaluate its antitumor efficacy alone or in combination with Paclitaxel in breast cancer mice model. Ehrlich induced mice mammary solid tumor model was used in the study. Mice were treated with oral rosmarinic acid and intraperitoneal Paclitaxel. Inflammation, angiogenesis, and apoptosis were checked. Enzyme linked immunosorbent assay (ELISA), quantitative real time PCR, and immunohistochemical methods were performed. Rosmarinic acid used prior to tumor induction suppressed NF-κB, TNF-α, vascular endothelial growth factor (VEGF) serum levels, and VEGF receptors. It also triggered apoptosis by restoring the levels of P53, Bcl-2, Bax, and caspase-3. Furthermore, in Ehrlich solid tumor mice, rosmarinic acid, and/or Paclitaxel significantly suppressed tumor growth with an increase in apoptotic markers P53 and Caspase-3 levels, and suppressed the Bcl2/Bax ratio.Rosmarinic acid exerted chemo-preventive and therapeutic potential alone or in combination with Paclitaxel. Moreover, rosmarinic acid targets numerous signaling pathways associated with breast cancer.

Biomedical features and therapeutic potential of rosmarinic acid

“…RA exhibited chemo-preventive effects alone and combined with Paclitaxel drug in breast cancer mice models. RA significantly suppressed NF-κB, VEGF, TNF-α expression and restored P53, Bcl-2, Bax, and caspase-3 levels, causing apoptosis (Mahmoud et al 2021 ). Interestingly, in another study, Zhou et al ( 2022 ) reported RA-based reduction in pancreatic ductal adenocarcinoma by restraining Gli translocation and facilitating proteasomal degradation.…”

Recent updates on anticancer mechanisms of polyphenols

“…RA induced apoptosis by restoring the expressions of Bcl-2, Bax, and caspase-3. In Ehrlich solid tumor mice, RA, in combination with paclitaxel, significantly decreased the growth of the tumor with enhancement in levels of apoptotic markers ( Mahmoud et al, 2021 ).…”

Salvia miltiorrhiza in Breast Cancer Treatment: A Review of Its Phytochemistry, Derivatives, Nanoparticles, and Potential Mechanisms

“…The tumor size treated with RA and paclitaxel combination showed a significant reduction. Hence, RA may increase the sensitivity of breast cancer cells to paclitaxel through the NF-κB-p53-caspase-3 pathway ( Mahmoud et al, 2021 ). The synergistic effects of CPT, Sal A, Tan IIA, and RA for breast cancer treatment are shown in Table 1 .…”

“…Interestingly, it was demonstrated that RA could dose-dependently inhibit the migration of MDA-MB-231BO bone-homing, MCF-7, MDA-MB-231, and MDA-MB-468 breast cancer cells ( Xu et al, 2010 ; Juskowiak et al, 2018 ; Messeha et al, 2020 ; Yahia Darwish et al, 2020 ). In addition, RA significantly improved the therapeutic effect of paclitaxel in an Ehrlich’s ascites carcinoma suspension-induced breast cancer mouse model ( Mahmoud et al, 2021 ).…”

“…Noteworthily, the efficacy of RA in MDA-MB-231 cells was weak, as exhibited with an up-regulation of HRK, TNFRSF25, and BNIP3, and down-regulation of TNFRSF11B ( Messeha et al, 2020 ). Another study indicated that RA and/or paclitaxel inhibited tumor growth in breast cancer models by increasing the levels of P53 and caspase-3 and inhibiting the Bcl2/Bax ratio ( Mahmoud et al, 2021 ). Their regulatory effects on apoptosis are shown in Figure 2 .…”