Salidroside Induces Apoptosis in Human Gastric Cancer Cells <i>via</i> the Downregulation of ENO1/PKM2/GLUT1 Expression

Abstract

Salidroside is reported to have a wide range of pharmacological properties and has been proven to play a key anti-cancer effect. This study investigated the effects of purified salidroside, an ingredient of Rhodiola rosea, on the proliferation of two human gastric cancer cell lines and further investigating its possible molecular mechanisms. We verified that salidroside exerts a dose-dependent inhibitory effect on the proliferation of SGC-7901 and MKN-45 human gastric cancer cells. Moreover, salidroside can induce cell apoptosis, which was accompanied by an increase in nuclear fragmentation. In addition, salidroside inhibited glycolysis, as evidenced by the reduced expression levels of the glycolysis-related enzymes pyruvate kinase isoenzyme M2 (PKM2), enolase 1 (ENO1) and glucose transporter 1 (GLUT1), which could play important roles in the metabolism of gastric cancer cells. Further investigation showed that salidroside exerted potent anti-proliferative effects by inhibiting glycolysis in human gastric cancer cells in vitro. In vivo, xenograft tumors treated with salidroside were significantly smaller than those in the control animals.Therefore, salidroside could be a promising therapeutic prospect in the treatment of gastric cancer.

The significance of glycolysis in tumor progression and its relationship with the tumor microenvironment

“…Xiao et al (2018) showed that GLUT1 knockdown inhibits prostate cancer growth by suppressing tumor-cell glycolysis and proliferation while promoting cell cycle arrest. Similarly, other researchers reported that GLUT1 deficiency also inhibited CRC cell proliferation, migration, and glycolysis (Zhang et al, 2020b), while reversing the Warburg effect in gastric cancer cells, while enhancing cellular apoptosis (Dai et al, 2021). Dihydroartemisinin and rhodopsin are also reported to exert anticancer effects by inhibiting GLUT1 (Gao et al, 2020;.…”

Phenolic Compounds of Rhodiola rosea L. as the Potential Alternative Therapy in the Treatment of Chronic Diseases

“…Salidroside enhanced doxorubicine sensitivity of HeLa-ADR-luc cells through the regulation of PI3K/Akt/HIF-1α and doxorubicine-induced resistance pathways, and exerted cardioprotective activity [133]. Salidroside suppressed chronic myeloid leukemia cell proliferation and induces apoptosis by regulating the miR-140-5p/wnt5a/β-catenin axis [134], and induced apoptosis in human gastric cancer cells via the downregulation of ENO1/PKM2/GLUT1 expression [135].…”

Traditional Chinese medicine monomers: Targeting pulmonary artery smooth muscle cells proliferation to treat pulmonary hypertension

“…The main bioactive ingredient isolated from Rhodiola rosea is called salidroside, which was found to have a variety of biological properties such as anti-inflammation, anti-oxidation, anti-stress, and anti-cancer [ [167] , [168] , [169] , [170] , [171] ]. Bioactive components of Rhodiola rosea inhibited the degradation of p27 Kip1 via down-regulating the expression of PCNA, cyclin D1, and CDK4 in lung tissue of PH rat model induced by hypobaric hypoxia, which contributed to reduction of mPAP and RVHI [ 172 ].…”