Ginsenoside Rg2 Attenuated Trastuzumab-Induced Cardiotoxicity in Rats

Abstract

Aim. Trastuzumab (TZM) is a monoclonal antibody drug for HER2-positive breast cancer by targeting epidermal growth factor 2, but it has significant cardiotoxicity. Ginsenoside Rg2 has shown a variety of biological activities. This study was aimed at investigating whether Rg2 attenuates TZM-induced cardiotoxicity. Methods. A model of TZM-induced cardiotoxicity was established in Wistar rats, and the rats were pretreated with Rg2. After echocardiography analysis, the rats were killed and the hearts were dissected for RNAseq analysis. Primary human cardiomyocytes (HCMs) were treated with TZM with or without pretreatment with Rg2 and then subjected to a colony formation assay, flow cytometry analysis, and Western blot analysis for the detection of caspase-3, caspase-9, and BAX. Results. TZM induced LV dysfunction in rats, but Rg2 could attenuate TZM-induced LV dysfunction. The mRNA levels of caspase-3, caspase-9, and BAX were significantly higher in TZM-treated rats. The colony formation ability of HCMs was significantly lower in TZM-treated cells but was recovered after pretreatment with Rg2. The apoptosis rate of HCMs was significantly higher in TZM-treated cells but was significantly lower after pretreatment with Rg2. Moreover, protein levels of caspase-3, caspase-9, and BAX were significantly higher in TZM-treated cells but were significantly lower after pretreatment with Rg2. Conclusion. Ginsenoside Rg2 inhibited TZM-induced cardiotoxicity, and the mechanism may be related to the downregulation of the expression of proapoptotic proteins caspase-3, caspase-9, and BAX and the inhibition of TZM-induced apoptosis in cardiomyocytes. Ginsenoside Rg2 has a potential to be applied in patients with breast cancer to prevent TZM-induced cardiotoxicity.

Ginsenoside Rg2 Attenuates Doxorubicin-induced Cardiomyocyte Apoptosis via the PI3K/Akt Pathway

“…Ginsenoside Rd was also reported to attenuate the mitochondria-dependent apoptotic pathway via Akt/GSK-3β signaling in myocardial ischemia/reperfusion injury (Wang et al 2013). Ginsenoside Rg2 (1) was previously reported to be capable of relieving cardiotoxicity induced by trastuzumab (Liu et al 2022), but no report on DOX. In our study, the anti-apoptotic function of ginsenoside Rg2 in DOXtreated cells was confirmed using TUNEL staining, of which the effect was dose-dependent.…”

Research progress of ginseng in the treatment of gastrointestinal cancers

“…GS also plays a significant role in immunotherapy and targeted therapy (Jiang et al, 2017;Liu J et al, 2022). Jiang et al observed that GRg3 enhances the anti-proliferative activity of erlotinib in pancreatic cancer cell lines by downregulating the EGFR/ PI3K/Akt signaling pathway (Jiang et al, 2017).…”

“…C-K blocked the interaction between membrane-linked protein A2 and the NF-кB p50 subunit and its nuclear co-localization, inhibited NF-кB activation, upregulated caspase-9 and caspase-3 expressions, and promoted apoptosis ( Wang X et al, 2019 ). Liu et al observed that C-K upregulates p21, a downstream target of RUNX3, arrests the cell cycle in the G0/G1 phase, and induces apoptosis ( Liu G et al, 2022 ). Reportedly, C-K induced apoptosis by inhibiting caspase and p53-dependent LGR5 expression in HCT116 colorectal cells ( Pak et al, 2020 ) and blocking HT-29 colorectal cells from entering the G1 phase, and C-K showed significant anti-inflammatory effects even at low concentrations ( Yao et al, 2018 ).…”

Progress on the efficacy and mechanism of action of panax ginseng monomer saponins treat toxicity

“…Rg2 induces autophagy in human cardiomyocytes (HCMs) by upregulating the expression levels of (p)-Akt, p-mTOR, beclin 1, light chain 3 (LC3) and autophagy protein 5 (ATG5), thereby treating TZM-induced cardiotoxicity ( Liu et al, 2021 ). Liu et al (2022) suggested that Rg2 could inhibit TZM-induced cardiac cytotoxicity. The mechanism might be related to the downregulation of proapoptotic proteins caspase-3, caspase-9, and BAX expression, which inhibited TZM-induced apoptosis in cardiac myocytes.…”