Plumbagin restrains hepatocellular carcinoma angiogenesis by suppressing the migration and invasion of tumor-derived vascular endothelial cells

Abstract

Tumor occurrence and development are very complicated processes. In addition to the roles of exogenous carcinogenic factors, the body's internal factors also play important roles. These factors include the host response to the tumor and the tumor effect on the host. In particular, the proliferation, migration and activation of endothelial cells are involved in tumor angiogenesis. Angiogenesis is one of the hallmarks of cancer. In this study, we investigate whether plumbagin can abrogate angiogenesis-mediated tumor growth in hepatocellular carcinoma (HCC) and, if so, through which molecular mechanisms. We observed that in co-cultures of the human endothelial cell line EA.hy926 and the human hepatoma cell line SMMC-7721 and Hep3B, the hepatoma cells induced migration, invasion, tube formation and viability of the EA.hy926 cells in vitro, and these processes were inhibited by plumbagin. Real-Time PCR, Western Blot and Immunofluorescence staining showed that plumbagin treatment suppressed expression of angiogenesis pathways (PI3K-Akt, VEGF/KDR and Angiopoietins/Tie2) and angiogenic factors (VEGF, CTGF, ET-1, bFGF),which is associated with tumor angiogenesis in cancer cells and xenograft tumor tissues. Furthermore, plumbagin was also found to significantly reduce tumor growth in an orthotopic HCC mouse model and to inhibit tumor-induced angiogenesis in HCC patient xenografts. Taken together, our findings strongly suggest that plumbagin might be a promising anti-angiogenic drug with significant antitumor activity in HCC.

Glycyrrhetinic acid binds to the conserved P-loop region and interferes with the interaction of RAS-effector proteins

“…administered Kobe (80 mg/kg) daily. Tumour volumes ( V ) were calculated using previously described methods 33 .…”

17β-Estradiol Promotes Angiogenesis of Rat Cardiac Microvascular Endothelial Cells In Vitro

“…Immunofluorescence staining was performed as reported previously [ 9 ]. In brief, rat CMECs on coverslips were washed once with PBS, fixed in 4% paraformaldehyde (pH 7.2~7.6) for 20 min at room temperature, washed with PBS, and then blocked with 5% bovine serum albumin in TBST for 15 min.…”

Plumbagin Triggers ER Stress-Mediated Apoptosis in Prostate Cancer Cells via Induction of ROS

“…It is roughly estimated that half of modern marketed drugs originate from natural products [8]. Plumbagin (PLB), a natural naphthoquinone isolated from the traditional folk medicines Plumbago zeylanica , was recently identified as selectively toxic to cancer cells in vitro and in vivo [9-11]. The roots of Plumbago zeylanica have been used in Indian medicine for more than 2, 500 years for treatments of various diseases [11].…”