Ginsenoside Rg5 Inhibits Human Osteosarcoma Cell Proliferation and Induces Cell Apoptosis through PI3K/Akt/mTORC1‐Related LC3 Autophagy Pathway

Abstract

The function and mechanism underlying the suppression of human osteosarcoma cells by ginsenoside-Rg5 (Rg5) was investigated in the present study. MG-63, HOS, and U2OS cell proliferation was determined by MTT assay after Rg5 treatment for 24 h. Rg5 inhibited human osteosarcoma cell proliferation effectively in a dose-dependent manner. The range of effective inhibitory concentrations was 160-1280 nM. Annexin V-FITC and PI double-staining assay revealed that Rg5 induced human osteosarcoma cell apoptosis. Western blotting, qRT-PCR, and FACS experiments revealed that Rg5 inhibited human osteosarcoma cells via caspase-3 activity which was related to the LC3-mediated autophagy pathway. Rg5 decreased the phosphorylation of PI3K, Akt, and mTORC1 activation. In contrast, LC3-mediated autophagy and caspase-3 activity increased significantly. A PI3K/AKT stimulator, IGF-1, reversed Rg5-induced cell autophagy and apoptosis in MG-63 cells. Collectively, the current study demonstrated that Rg5 induced human osteosarcoma cell apoptosis through the LC3-mediated autophagy pathway. Under physiological conditions, activation of PI3K/AKT/mTORC1 inhibits LC3 activity and caspase-3-related cell apoptosis. However, Rg5 activated LC3 activity by inhibiting the activation of PI3K/AKT/mTORC1. The present study indicated that Rg5 could be a promising candidate as a chemotherapeutic agent against human osteosarcoma.

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

“…The natural product, ginsenoside Rg5, was reported to trigger human osteosarcoma cell apoptosis via the LC3-mediated autophagy pathway by inhibiting the activation of PI3K/Akt/mTORC1. 231 …”

“…The natural product, ginsenoside Rg5, was reported to trigger human osteosarcoma cell apoptosis via the LC3-mediated autophagy pathway by inhibiting the activation of PI3K/Akt/mTORC1. 231 In addition to the small molecules mentioned above, more small molecules showed potent antitumor activity via the regulation of autophagy. For example, AZD2014, as a dual mTOR inhibitor, could suppress proliferation and induce autophagy to sensitize thyroid undifferentiated carcinoma (ATC) cells to paclitaxel (PTX).…”

Transcriptome Analysis of the Anti-Proliferative Effects of Ginsenoside Rh3 on HCT116 Colorectal Cancer Cells

“…Many studies have examined the effects of Rh2 on different tumor cells and documented that it inhibited cell proliferation, induced apoptosis, and arrested the cell cycle [ 23 , 24 , 25 , 26 ]. Other tetracyclic triterpenoids, such as ginsenoside Rg3 [ 27 ], Rg5 [ 28 ] and compound K [ 29 ], can also inhibit tumor cell proliferation. These results suggested that the tetracyclic triterpene ring of these compounds may be responsible for their anti-tumor function.…”

Pharmacological Effects of Resveratrol in Intervertebral Disc Degeneration: A Literature Review

“…Autophagy is a self‐protective cellular mechanism that removes damaged or senescent organelles, and considered to be an important cellular metabolic process 85,86 . The exact role of autophagy in IDD remains controversial.…”

“…Autophagy is a self‐protective cellular mechanism that removes damaged or senescent organelles, and considered to be an important cellular metabolic process. 85 , 86 The exact role of autophagy in IDD remains controversial. At present, most studies reported that the activation of autophagy could ameliorate IDD progression, while relatively few studies showed that excessive activation of autophagy could accelerate IDD progression.…”