Astragaloside IV Induces Apoptosis, G₁-Phase Arrest and Inhibits Anti-apoptotic Signaling in Hepatocellular Carcinoma

Abstract

Background/Aim: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and the third leading cause of cancer death worldwide. Although multiple chemotherapies options are available for HCC, chemoinduced toxicity is inevitable during clinical treatment. Therefore, identifying possible adjuvant agents with both liver-protective and antitumor effects is critical. Herbal medicines have chemopreventive and anti-HCC effect, such as Juzen taiho-to and Sho-saiko-to. Astragaloside IV is a compound extracted from the Chinese medical herb Astragalus membranaceus (Fisch.) Bge. with liver protection potential. However, whether astragaloside IV may also possess tumor-inhibitory capability and its underlying mechanism is remaining unknown. Materials and Methods: Viability analysis, cell-cycle analysis, apoptosis analysis, western blotting analysis and invasion trans-well assay were performed to identify tumor-inhibitory potential of astragaloside IV on HCC cells (SK-Hep1 and Hep3B cells). Results: We found that astragaloside IV may induce cytotoxicity and extrinsic/intrinsic apoptosis effect, but also trigger G 1 arrest in HCC cells. The expression of anti-apoptotic proteins of HCC were all reduced by astragaloside IV. Additionally, astragaloside IV also suppressed HCC cell invasion ability. Conclusion: Astragaloside IV effectively suppressed HCC cell proliferation, invasion and antiapoptosis in vitro.

Astragaloside IV Suppresses Hepatic Proliferation in Regenerating Rat Liver after 70% Partial Hepatectomy via Down-Regulation of Cell Cycle Pathway and DNA Replication

“…Additionally, our results could be used as basic study data for the anti-cancer activities of AS-IV with other studies. In recent, similar anti-cancer effects of AS-IV were reported including blocking of MAPK signal, decreased PCNA and Ki67 expression, and trigging G1 arrest in tumor cell [ 45 , 50 ].…”

Anticancer effects and mechanisms of astragaloside‑IV (Review)

“…This study suggested that AS-IV suppresses HCC cell proliferation and growth via both the extrinsic and intrinsic apoptotic pathways (Fig. 2) (31).…”

“…In addition, a transwell invasion assay suggested that numbers of invading SK-Hep1 and Hep3B cells were significantly reduced by AS-IV (31). Assessment of the invasion of cervical cancer cells treated with AS-IV indicated that it significantly reduced cancer cell invasion of HeLa and SiHa cells.…”

Astragaloside IV protects against oxidized low‐density lipoprotein‐induced injury in human umbilical vein endothelial cells via the histone deacetylase 9 (HDAC9)/NF‐κB axis

“…ASV has extensive activities on the hematopoietic system, liver, endocrine system, nervous system, collagen metabolism, cardiac function, and organ immune system 37 . For example, ASV showed the inhibition influence on anti‐apoptotic signaling and enhancement on apoptosis in hepatocellular carcinoma 38 . Furthermore, ASV treatment modulated neuronal apoptosis through regulating the lincRNA‐p21/CHOP axis in Parkinson's disease 39 .…”