likviriton and Stomach-Neoplasms

Gastric cancer is one of the most factors, leading to cancer-related death worldwide. However, the therapies to prevent gastric cancer are still limited and the emergence of drug resistance leads to development of new anti-cancer drugs and combinational chemotherapy regimens. Our study was aimed to explore the anti-gastric cancer effects of liquiritin (LIQ), a major constituent of Glycyrrhiza Radix, which possesses a variety of pharmacological activities. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially inhibited tumor cells over other normal cells, when used in alone or in combination. The results indicated that LIQ, when applied in single, was moderately effective to suppress proliferation, and migration, as well as to induce apoptosis and reactive oxygen species (ROS) generation of human gastric cancer cell lines, AGS and SNU-216, which are TRAIL-resistant. Significantly, when used in combination, the two drugs functioned synergistically to impede the progression and growth of human gastric cancer cells in vitro and gastric cancer cell xenograft nude mice in vivo. Both intrinsic and extrinsic apoptosis were induced by the two in combination via activating Caspases. And c-Jun N-terminal kinase (JNK) activity was dramatically induced by TRAIL/LIQ. Importantly, TRAIL/LIQ-triggered apoptosis and JNK were dependent on ROS production. The data indicated that application of TRAIL/LIQ in combination had a potential value for clinical use to synergistically prevent human gastric cancer development.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Flavanones; Glucosides; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Reactive Oxygen Species; Stomach Neoplasms; TNF-Related Apoptosis-Inducing Ligand; Xenograft Model Antitumor Assays

Gastric cancer is reported as one of the leading factors resulting in tumor-related death worldwide. However, the therapies to suppress gastric cancer are still limited and the emergence of drug resistance makes it necessary to develop new and effective anticancer drugs and combinational chemotherapy schemes. Liquiritin (LIQ) is a major constituent of Glycyrrhiza Radix, exhibiting various pharmacological activities, including anticancer. In this study, we investigated the role of LIQ in human gastric cancer cells with cisplatin (DDP) resistance. The findings suggested that LIQ, when applied in single therapy, could moderately inhibit the proliferation and migration of DDP-resistant gastric cancer cells, SGC7901/DDP. DDP and LIQ in combination induced G0/G1 cell cycle arrest to suppress the proliferation of gastric cancer cells, which were associated with the decrease of cyclin D1, cyclin A and cyclin-dependent kinase 4 (CDK4) and increase of p53 and p21. In addition, LIQ combined with DDP significantly induce apoptosis and autophagy both in vitro and in vivo through enhancing cleavage of caspase-8/-9/-3 and PARP, as well as LC3B and Beclin 1 expression. Significantly, the two drugs, when used in combination, prevented gastric cancer cell xenografts in nude mice in vivo. Together, the results revealed that application of DDP and LIQ in combination possessed a potential value against the growth of human gastric cancer with DDP resistance.

Topics: Animals; Apoptosis; Autophagy; Cell Line, Tumor; Cell Proliferation; Cisplatin; Drug Resistance, Neoplasm; Flavanones; Glucosides; Glycyrrhiza; Humans; Mice; Plant Extracts; Stomach Neoplasms; Xenograft Model Antitumor Assays