Targeting ER Stress with Saikosaponin A to Overcome Resistance under Radiation in Gastric Cancer Cells

Abstract

Saikosaponin A is a triterpene saponin and a potentially bioactive compound derived from Bupleurum falcatum L. However, the molecular mechanisms and effects of saikosaponin A in gastric cancer remain unknown. In the present study, I evaluated the effects of saikosaponin A on cell death and endoplasmic reticulum stress via calcium and reactive oxygen species release. Targeting reactive oxygen species with diphenyleneiodonium and N-acetylcysteine inhibited cell death and protein kinase RNA-like ER kinase signaling pathway by down-regulating Nox4 and inducing glucose-regulated protein 78 exosomes. Furthermore, saikosaponin A caused a synergistic inhibitory effect of the epithelial mesenchymal transition phenomenon, indicating the reversible phenotype modulation by epithelial cells under radiation exposure in radiation-resistant gastric cancer cells. These results suggest that saikosaponin A-mediated calcium and reactive oxygen species-induced endoplasmic reticulum stress overcome radio-resistance and induce cell death under radiation in gastric cancer cells. Therefore, saikosaponin A in combination with radiation may be a potential strategy for gastric cancer therapy.

Reactive oxygen species nanoamplifiers with multi-enzymatic activities for enhanced tumor therapy

“…The dosage of the nanomedicine used for in vivo cancer therapy was based on the consideration of safety, therapeutic effects and previous reports. According to the previously reported literature studies on in vivo cancer therapy, the total dosage of SSA ranged from 5 to 10 mg kg −1 , 37,38 while the dosage of CeO 2 used ranged from 5 to 30 mg kg −1 . 39,40 Herein, the total dosage of SSA (3 × 1.4 mg kg −1 ) and Ce (3 × 5 mg kg −1 ) is significantly lower than the reported maximum dosage.…”

Paeoniflorin Induces ER Stress-Mediated Apoptotic Cell Death by Generating Nox4-Derived ROS under Radiation in Gastric Cancer

“…Previous studies have shown that radiation combined with the natural product nodakenin overcomes radioresistance by activating ROS, ER stress, and apoptosis in vivo and in vitro in radio-resistant breast cancer models [83]. Radiation combined with the natural product saikosaponin A overcomes radioresistance via the induction of apoptotic cell death in vitro and in vivo in radio-resistant gastric cancer models [84]. The natural flavonoid fisetin combined with radiation also overcomes radioresistance and has a powerful anti-cancer effect in vitro and in vivo in radio-resistant liver cancer models [85].…”

The circadian clock gene, BMAL1, promotes radiosensitization in nasopharyngeal carcinoma by inhibiting the epithelial-to-mesenchymal transition via the TGF-β1/Smads/Snail1 axis

“…To account for the build-up effect, 25cm 2 culture asks were entirely lled with culture medium and set in a water phantom. To create the radioresistant cell line 5-8FR, clinically conventional fractionated irradiation was utilized to dispose the 5-8F (2 Gy per fraction, 1 fraction per day, 5 days per week) [23]. The 5-8F proteins at 10 Gy/1 week, 30 Gy/3 week, 50 Gy/5 week, 70 Gy/7 week were obtained during the period.…”