The effects of Alisol B 23-acetate in hepatocellular carcinoma via inducing cell apoptosis and inhibiting cell migration and invasion

Abstract

Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from Chinese herbal medicine and has a variety of biological functions, especially anti-cancer e ects. However, the e ects and mechanisms of AB23A in hepatocellular carcinoma (HCC) remain unclear. Cell viability, invasion and migration were measured by MTT, Transwell and wound healing assays, respectively. To detect cell cycle and apoptosis, a ow cytometry assay was used. Tumor xenogra experiment was performed to measure tumor growth. e enzymatic assay was used to determine the activity of matrix metalloproteinase (MMP)-2 and-9. Furthermore, the mRNA and protein levels of Bcl-2, Bax, Caspase-3/-9, MMP-2/-9 and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) were detected by RT-PCR and Western blotting assays. AB23A suppressed cell viability in a concentration-dependent manner, blocked cell cycle, and induced apoptosis via up-regulating Bax, Caspase-3 and Caspase-9, and down-regulating Bcl-2 in HCC cells both in vitro and in vivo. In addition, AB23A inhibited cell invasion and migration through down-regulating MMP-2/-9 activities. e e ects of AB23A might be associated with the PI3K/Akt signaling pathway in HCC cells. Taken together, the present data demonstrated that AB23A might play a role in suppressing the progression of HCC, revealing the value of AB23A for hepatocellular carcinoma treatment in clinic.

Promising Anticancer Activities of Alismatis rhizome and Its Triterpenes via p38 and PI3K/Akt/mTOR Signaling Pathways

“…Similarly, AB23A suppressed HepG2 cell growth by inducing G1 arrest and increasing the percentage of apoptotic cells without affecting LO2 normal cells [ 29 ]. In addition to in vitro models, AB23A significantly reduced tumor volume and weight by inducing apoptosis in BALB/c mice inoculated with SK-HEP-1 [ 30 ] ( Table 1 ).…”

“…AB23A possesses antimetastatic effects in human non-small cell lung cancer A549, human hepatoma SK-HEP-1, and human ovarian cancer HEY cells. In particular, AB23A significantly decreased SK-HEP-1 and HEY cell migration and invasion by inhibiting MMP-2 and MMP-9 protein and gene expression [ 30 , 33 ]. Similar to AA, MMP downregulation by AB23A is mediated by the blockade of PI3K/AKT phosphorylation [ 30 ] ( Table 2 ).…”

“…In particular, AB23A significantly decreased SK-HEP-1 and HEY cell migration and invasion by inhibiting MMP-2 and MMP-9 protein and gene expression [ 30 , 33 ]. Similar to AA, MMP downregulation by AB23A is mediated by the blockade of PI3K/AKT phosphorylation [ 30 ] ( Table 2 ).…”

“…The downregulation of the Akt/mTOR pathway was also involved in the inhibition of cell migration and invasion by the treatment of AA in MDA-MB-231 [ 18 ]. AB23A induced mitochondrial apoptosis through the regulation of PI3K/Akt pathway in A549 [ 28 ], SK-HEP-1 [ 30 ], and SGC7901 [ 24 ] cells, which resulted in overgrowth inhibition of cancer.…”

“…Interestingly, the treatment of MDA-MB-231 cells with AA and AB was associated with a significant cytotoxicity via the activation of p38 and the blockade of Akt/mTOR and NFκB signaling simultaneously [ 18 , 22 ]. Among the mechanisms frequently observed after the treatment of AR and its triterpenes in human cancer cells, the PI3K/Akt/mTOR pathway is likely to be the most frequently interrupted pathway [ 18 , 21 , 22 , 24 , 28 , 29 , 30 ]. In particular, the antiproliferative and antimetastatic activities of AB23A in SK-HEP-1 cells via the PI3K/Akt pathway [ 30 ] and AA in MDA-MB-231 cells via the Akt/mTOR pathway [ 18 ] can offer clinical applicability for the treatment of tumors and the prevention of metastasis.…”