Betulinic acid triggers apoptosis and inhibits migration and invasion of gastric cancer cells by impairing EMT progress

Abstract

Gastric cancer (GC) is one of the most prevalent types of malignancies. Betulinic acid (BA) is a natural pentacyclic triterpene with a lupine structure. However, to the best of our knowledge, there is no research study on the anti-tumour and anti-metastasis effect of BA on GC. In this study, we assessed the anti-cancer effect of BA on human GC cells in vitro and in vivo. We first investigated the cytotoxicity and antiproliferation effect of BA on GC cells of SNU-16 and NCI-N87. The results indicated that BA had significant cytotoxic and inhibitory effects on GC cells in a dose-and time-dependent manner. To further study the cytotoxic action of BA on GC cells, we assessed the apoptotic induction effect of BA on SNU-16 cells and found that BA distinctly induced apoptosis in SNU-16 cells. In addition, BA inhibited the migratory and invasive abilities of SNU-16 cells. Western-blot analysis revealed that BA suppressed the migration and invasion of GC cells by impairing epithelialmesenchymal transition progression. Furthermore, in vivo experiments showed that BA could delay tumour growth and inhibit pulmonary metastasis, which is consistent with the results of in vitro studies. Overall, we evaluated the anti-cancer effect of BA on human GC cells in vivo and in vitro, and the present study provides new evidence on the use of BA as a potential anti-cancer drug for GC treatment. Significance of the study: BA significantly suppressed proliferation and triggered apoptosis in GC cells. Additionally, BA remarkably inhibited migration and invasion of GC cells by impairing the epithelial-mesenchymal transition signalling pathway. It is worth noting that BA drastically retarded tumour growth in the xenograft mouse model of GC. Our results indicated that BA can be considered a candidate drug for GC therapy.

Potential roles and molecular mechanisms of phytochemicals against cancer

“…68 Betulinic acid, a naturally occurring pentacyclic triterpenoid with a lupine structure, and normally found in the bark of birch trees, evidently inhibits the epithelial–mesenchymal transition signaling pathway to block gastric cancer cell migration and invasion in vivo and in vitro . 69…”

Betulinic acid induces apoptosis and impairs migration and invasion in a mouse model of ovarian cancer

“…BA could significantly suppress activity of EMT by upregulating epithelial protein and downregulating mesenchymal protein simultaneously. Previous study demonstrated that BA triggers apoptosis and inhibits migration and invasion of gastric cancer cells by impairing EMT progress (Chen et al., 2020). Sun et al showed that BA can inhibit stemness and EMT of pancreatic cancer cells via activation of AMPK signaling (Sun et al., 2019).…”

“…BA could also downregulate expression of MMP2 and MMP9, resulting in a suppression of tumor cells migration and invasion (Wang et al., 2019; Yang, Li, Fu, Jiang, & Meng, 2018; Zeng et al., 2018). It is reported that BA could suppress breast cancer cell migration and invasion by impairing epithelial‐mesenchymal transition (EMT) (Chen, Wu, Liu, & Zhou, 2020). The BA has gradually become one of the hot spots in the research of anticancer drug compounds.…”

Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers

“…In colon cancer, metabolomics have revealed the mechanisms underlying novel cancer treatments using Chinese herbal medicines. Yang et al used an UPLC-MS/MS assay to identify that shikonin could inhibit CRC cell growth via various signaling pathways that included glutathione metabolism, arginine biosynthesis, purine metabolism, betaalanine metabolism, and arginine biosynthesis (Chen et al, 2020b). Daddiouaissa et al (2021)performed metabolic profiling and utilized multivariate data analysis combined with an ingenuity pathway analysis (IPA) to explore the effects of treating CRC cells with the ionic liquid-Graviola fruit pulp extract (IL-GPE).…”