Selective anticancer effects of Serjania marginata Casar. extract in gastric cells are mediated by antioxidant response

Abstract

Gastric cancer is the fifth most common malignancy worldwide. Serjania marginata Casar. (SM) displays anti-inflammatory properties and has been used to treat gastrointestinal disorders. In the current study, we examined whether the hydroethanolic extract of SM leaves exerted cytotoxic, mutagenic, and protective effects in nontumor gastric epithelium cells (MNP01) and gastric adenocarcinoma cells (ACP02) in vitro and analyzed whether its action was selective. Initially, cell viability (MTT assay), cell cycle kinetics (flow cytometry), and cell proliferation (total protein content) were analyzed. In addition, genomic instability (cytokinesis-block micronucleus cytome assay), anti/pro-oxidant status (CM-H 2 DCFDA probe), and transcriptional expression (RT-qPCR) of genes related to cell cycle, cell death, and antioxidant defense were also evaluated. The SM extract was cytotoxic toward MNP01 and ACP02 cells at concentrations greater than 300 and 100 μgÁml À1 , respectively, and decreased protein content only toward ACP02 cells at 200 μg ml À1 . In ACP02 cells, the SM extract at 100 μgÁml À1 associated with doxorubicin (DXR; 0.2 μg ml À1 ) clearly promoted cell cycle arrest at the G2/M phase. The extract alone was not mutagenic to either cell type and reversed DXR-induced DNA damage and H 2 O 2 -induced oxidative stress in MNP01 cells. The gene expression experiments showed that SM hydroethanolic extract exerts an antioxidant response via NFE2L2 activation in nontumor gastric cells, and cell cycle arrest (G2/M) in ACP02 gastric cancer cells via the TP53 pathway. The selective action of SM indicates that it is a promising therapeutic agent to treat gastric diseases and merits further studies.

H3K27 acetylation activated‐CD109 evokes 5‐fluorouracil resistance in gastric cancer via the JNK/MAPK signaling pathway

“…In recent years, development of molecular drugs, new compounds and traditional Chinese medicine targeting oncogenic pathways have been found to be used to treat GC. [19][20][21][22] 5-FU is one of the first-line chemotherapeutic agents against several cancers, which is widely applied in clinical practice. [23][24][25] However, 5-FU resistance results in terrible chemotherapy efficacy and patients' prognosis.…”