Sesquiterpenoid bilobalide inhibits gastric carcinoma cell growth and induces apoptosis both in vitro and in vivo models

Abstract Gastric carcinoma is one of the most aggressive types of cancer that ranks fifth among all cancer incidences and third in cancer mortality. As it exhibits a prolonged asymptomatic condition and high recurrence rate, it is a great challenge to treat gastric cancer. Traditional medicine that utilizes herbal phytochemicals to treat various diseases is a potent alternative for current allopathic treatment. Hence, we evaluated the potency of a phytochemical bilobalide for treating gastric cancer in in vitro and in vivo models. Bilobalide, a sesquiterpenoid, is present in the Ginkgo biloba plant that belongs to the family of Ginkgoaceae. The cytotoxicity effect of bilobalide was evaluated in both gastric cancer (AGS) cells and normal gastric epithelial cells. Apoptosis‐inducing property of bilobalide against the AGS cell line was analyzed with different fluorescent staining techniques and terminal deoxynucleotidyl transferase dUTP nick‐end labeling assay, and cell cycle analysis was carried out by flow cytometry. The in vivo studies were assessed with N ‐methyl‐ N ‐nitrosourea (MNU)‐induced gastric cancer in rats. Serum‐specific gastric markers were quantified and histopathological analysis of stomach tissue was performed. The expression of target‐signaling molecules was analyzed by a reverse‐transcription polymerase chain reaction. The in vitro results proved that bilobalide effectively suppressed the AGS cell growth and induced cell death by nuclear damage and apoptosis induction. The bilobalide treatment effectively arrested the cell cycle of AGS cells via inhibiting the PI3K‐signaling pathway. Our in vivo results also confirmed that the bilobalide persuasively inhibited the MNU‐induced gastric carcinoma via inhibiting the thioredoxin‐fold family proteins and inflammatory markers' expression. Overall, our results authentically prove that bilobalide possesses therapeutic potency to cure gastric carcinoma.