Rosmarinic acid, the active component of Rubi Fructus, induces apoptosis of SGC-7901 and HepG2 cells through mitochondrial pathway and exerts anti-tumor effect

Abstract

Rosmarinic acid (RA) is a well-known phenolic acid widely present in over 160 species of herbal plants and known to exhibit anti-tumor effects on breast, prostate, and colon cancers in vitro. However, its effect and mechanism in gastric cancer and liver cancer are unclear. Moreover, there is no RA report yet in the chemical constituents of Rubi Fructus (RF). In this study, RA was isolated from RF for the first time, and the effect and mechanism of RA on gastric and liver cancers were evaluated using SGC-7901 and HepG2 cells models. The cells were treated with different concentrations of RA (50, 75, and 100 μg/mL) for 48 h, and the effect of RA on cell proliferation was evaluated by the CCK-8 assay. The effect of RA on cell morphology and mobility was observed by inverted fluorescence microscopy, cell apoptosis and cell cycle were determined by flow cytometry, and the expression of apoptosis-related proteins cytochrome C, cleaved caspase-3, Bax, and Bcl-2 was detected by western blotting. The results revealed that, with an increase in the RA concentration, the cell viability, mobility, and Bcl-2 expression decreased, while the apoptosis rate, Bax, cytochrome C, and cleaved caspase-3 expression increased, and SGC-7901 and HepG2 cells could be induced to arrest their cell cycle in the G0/G1 and S phases, respectively. These results together indicate that RA can induce apoptosis of SGC-7901 and HepG2 cells through the mitochondrial pathway. Thus, this study supplements the material basis of the anti-tumor activity of RF and provides an insight into the potential mechanism of RA-inducing apoptosis of gastric cancer SGC-7901 cells and liver cancer HepG2 cells, thereby facilitating further developmental studies on and the utilization of the anti-tumor activity of RF.

Rosemary: Unrevealing an old aromatic crop as a new source of promising functional food additive—A review

“…Carnosol can directly inhibit the chymotrypsin‐like activity of the 20S proteasome and the expression of matrix metalloproteinase‐9 (MMP‐9), thus achieving the migration inhibition of cancer cells (Allegra et al., 2020). Rosmarinic acid (RA) is a potent apoptosis inducer of SGC‐7901 and HepG2 cells via the mitochondrial pathway (Chen et al., 2023), and it has also been shown to inhibit cytokine‐induced mesangial cell proliferation and suppress platelet‐derived growth factor (PDGF) and c‐myc mRNA expression in PDGF‐stimulated mesangial cells in vitro (Makina et al., 2002). In addition, many pharmacological studies have shown that the bioactive compositions of flavone 4,7‐ O ‐dimethylapigenin, 7‐ O ‐methyl‐epi‐rosmanol, carnosol, carnosic acid, and betulinic acid in rosemary were able to block the activation of AhR by TCDD, thus inhibiting the cancer cell proliferation (Kallimanis et al., 2022).…”

Molecular Pathways of Rosmarinic Acid Anticancer Activity in Triple-Negative Breast Cancer Cells: A Literature Review

“…These cells constitute TNBC, an aggressive and metastatic subtype unaffected by hormone therapy [ 33 ]. We present a range of integrated chemical biology techniques aimed at using relevant mechanisms of action that might lead to major therapeutic advancements in the treatment of BC [ 3 , 4 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”