Natural product pectolinarigenin inhibits proliferation, induces apoptosis, and causes G2/M phase arrest of HCC via PI3K/AKT/mTOR/ERK signaling pathway

Abstract

BackgroundHepatocellular carcinoma (HCC) is characterized by considerable phenotypic and molecular heterogeneity, but the overall survival of HCC patients remains extremely poor. Thus, novel and efficient alternatives to antitumor agents are urgently needed. Pectolinarigenin, a flavonoid compound extract, has been previously reported for the treatment of nasopharyngeal cancer. However, the potential antitumor roles of pectolinarigenin in HCC have not been clearly elaborated. In the present study, we investigated its role in HCC treatment and explored the potential molecular mechanism(s).Materials and methodsHCC cell lines SMMC7721 and PLC5 were cultured and treated with indicated concentrations of pectolinarigenin. For the HCC cell proliferation, after HCC cells were stimulated with indicated concentrations of pectolinarigenin, the cell viability was detected in CCK-8 and colony-forming assays. HCC cell invasion/migration assay was performed by Transwell and wound scratch methods. Additionally, cellular apoptosis and cell cycle arrest analysis was performed with flow cytometric analysis. Finally, the involved underlying signaling pathway, the PI3K/AKT/mTOR/ERK signaling-related molecular markers were detected through Western blot methods with indicated antibodies. Meanwhile, antitumor activity of pectolinarigenin was also assessed in tumor-bearing mice.ResultsThe results indicated that the treatment with pectolinarigenin significantly inhibited cell proliferation and migratory and invasive abilities of SMMC7721 and PLC5 cells in concentration- and time-dependent manner. Meanwhile, pectolinarigenin markedly induced cell apoptosis and G2/M phase arrest in SMMC7721 and PLC5 cells, which was associated with apoptosis- and cell cycle-related protein levels, respectively. Furthermore, pectolinarigenin inhibited PI3K/AKT/mTOR/ERK signaling pathway. It also significantly suppressed HCC tumor growth in vivo.ConclusionPectolinarigenin could suppress the viability and motility and cause apoptosis and G2/M phase arrest in HCC cell lines by inhibiting the PI3K/AKT/mTOR/ERK signaling pathway. This might be an appealing potential therapeutic agent for HCC treatment.

M2 Macrophages Promote HCC Cells Invasion and Migration via miR-149-5p/MMP9 Signaling

“…To examine the detailed mechanisms underlying M2 macrophages' role in regulating HCC cells invasion and migration, we tested the expression of proteins that have been connected with cancer cell invasion and migration [12][13][14][15][16][17][18] in both culture alone and in co-culture. The exploratory experiments led to the focus on MMP9 as the results showed that MMP9 protein expression was increased after co-culture, both in SK-HEP-1 and HA22T HCC cells ( Fig.…”

MicroRNA‐378‐3p/5p represses proliferation and induces apoptosis of oral squamous carcinoma cells via targeting KLK4

“…In addition, the PI3K/AKT signalling pathway is also involved in the regulation of tumour progression. A previous study showed that pectolinarigenin suppressed the viability and caused apoptosis of hepatocellular carcinoma cells via the inactivation of PI3K/AKT signalling pathway . Convincing evidence showed that target regulating the PI3K/AKT/mTOR signalling pathway may enhance the radiosensitivity or chemosensitivity of OSCC .…”

Antinociceptive Effects of Shenling Baizhu through PI3K‐Akt‐mTOR Signaling Pathway in a Mouse Model of Bone Metastasis with Small‐Cell Lung Cancer

“…Our data showed that SLBZ-AP Many researchers confirmed that PI3K/Akt/mTOR signaling pathway is related to a few biological activities to affect cell proliferation, survival, and migration [7,8], especially to stimulate proliferation, survival, invasion/metastasis, and metabolic reprogramming and suppress autophagy, which is involved in possible mechanisms of oncogenic transformation [9]. PI3K/Akt/mTOR signaling pathway is commonly activated and suppression of its activation may inhibit cells proliferation and metastasis in cancers of the lung [10,11,50], colorectal [51,52], esophagus [53], breast [54][55][56], liver [57,58], and kidney [59,60], which has been considered a promising therapeutic target. Whether the PI3K/Akt/mTOR signaling pathway involved in SLBZ-AP affects BMLC was further explored in our study, results of which indicated that the mRNA and protein expression of AKT, mTOR, P70S6, and VEGF as well as protein expression of p-AKT, p-mTOR, p-P70S6, and VEGF was significantly increased in the marrow of tibia from BMLC mice.…”