4-Acetylantroquinonol B Suppresses Prostate Cancer Growth and Angiogenesis via a VEGF/PI3K/ERK/mTOR-Dependent Signaling Pathway in Subcutaneous Xenograft and In Vivo Angiogenesis Models

Abstract

Prostate cancer is a major cause of cancer-related mortality in men in developed countries. The compound, 4-acetylantroquinonol B (4AAQB), is isolated from Antrodia cinnamomea (commonly known as Niu-Chang-Chih), which has been shown to inhibit cancer growth. However, the anticancer activity of 4AAQB has not previously been examined in prostate cancer. This study aimed to investigate the effect of 4AAQB on cancer and angiogenesis, as well as to explore its mechanism of action. Human prostate cancer cells (PC3) and human umbilical vein endothelial cells (HUVEC) were used in cell viability, cell migration, and cell cycle functional assays to evaluate the anticancer and antiangiogenic efficacy of 4AAQB in vitro. The effects of 4AAQB in vivo were determined using xenograft and angiogenesis models. The signaling events downstream of 4AAQB were also examined. The 4AAQB compound inhibited PC3 cell growth and migration, and reduced in vivo cancer growth, as shown in a subcutaneous xenograft model. Furthermore, 4AAQB inhibited HUVEC migration, tube formation, and aortic ring sprouting; it also reduced neovascularization in a Matrigel implant angiogenesis assay in vivo. The 4AAQB compound also decreased metastasis in the PC3 prostate cancer model in vivo. Serum or vascular endothelial growth factor (VEGF)-induced VEGF receptor 2 (VEGFR2), phosphoinositide 3-kinase (PI3K)/Ak strain transforming (Akt), and extracellular signal-regulated kinase ½ (ERK ½) phosphorylation were attenuated by 4AAQB in both PC3 and HUVEC. In conclusion, 4AAQB is a potential candidate for prostate cancer therapy.

ZD6474 attenuates TGF-β1-induced fibrosis in human Tenon fibroblasts and inhibits neovascularization via AKT-mTOR signaling pathway

“…VEGF, the most important angiogenesis factor, can be activated by binding with VEGF, and then many downstream signal-transduction networks associated with neovascularization can be successively activated, such as PI3K/AKT/mTOR, ERK1/2, and many others, so VEGF is crucial for angiogenesis-related processes [ 43 ]. In several previous studies, VEGF activation is confirmed to be tightly associated with the activation of PI3K-AKT-mTOR signaling pathway [ 44 , 45 ].…”

Downregulation of miR-99b-5p and Upregulation of Nuclear mTOR Cooperatively Promotes the Tumor Aggressiveness and Drug Resistance in African American Prostate Cancer

“…Mammalian target of rapamycin (mTOR) regulates a wide range of cellular events including cell proliferation, protein translation, metabolism, regeneration, autophagy, and apoptosis [ 16 , 17 , 18 ]. In the context of molecular mechanism, mTOR plays a central role coordinating ERBB (also known as EGFR/PI3K/AKT) and VEGF signaling in the ERBB/mTOR/VEGF axis, a signaling network frequently upregulated in PCa [ 19 , 20 , 21 , 22 ]. In this study, we particularly focused on the reciprocal pairing miR-99b-5p/ MTOR , where miR-99b-5p is downregulated while MTOR is upregulated in AA PCa compared to EA PCa.…”

SALL4 correlates with proliferation, metastasis, and poor prognosis in prostate cancer by affecting MAPK pathway

“…The most potential acridone, buxifoliadine E, inhibited the proliferation of four cancer cell lines, namely prostate cancer (LNCaP), neuroblastoma (SH SY5Y), hepatoblastoma (HepG2), and colorectal cancer (HT29), by inhibiting the ERK pathway 39 . In prostate cancer, when ERK phosphorylation is attenuated, PC3 cell growth and angiogenesis can be inhibited 40 . Elevated levels of phosphorylated ERK was also confirmed in castration‐resistant PCa compared to untreated primary PCa 41 .…”