Angelicin inhibits liver cancer growth in vitro and in vivo

Abstract

Previous studies have reported that angelicin exerted antiproliferative effects on several types of tumor cell. However, to the best of our knowledge, the effects of angelicin monotherapy on human liver cancer remain to be investigated. In the present study, the antitumor activity of angelicin was evaluated in vitro and in vivo, and the molecular mechanisms underlying its effects were investigated. The present results revealed that angelicin induced apoptosis in liver cancer cells in a dose- and time-dependent manner. Furthermore, in HepG2 and Huh-7 cells, angelicin-induced apoptosis was demonstrated to be mitochondria dependent, involving the phosphatidylinositol-4,5-bisphosphate 3-kinase/RAC-α serine/threonine-protein kinase signaling pathway. In addition, administration of angelicin to mice bearing liver tumor xenografts inhibited tumor growth, without producing significant secondary adverse effects. These results suggested that angelicin may have potential as a novel therapeutic agent for the treatment of patients with liver cancer.

Angelicin—A Furocoumarin Compound With Vast Biological Potential

“…Hence, the changes seen in the expression of apoptotic and anti-apoptotic proteins by angelicin is a positive indicator that angelicin has anticancer properties. Besides that, several different cells, such as promyelocytic leukaemia (HL-60), human lung cancer (A549), hepatoblastoma (HepG2), and hepatocellular carcinoma (Huh-7) cell lines, also yielded the same changes in the proteins mentioned above when incubated with angelicin for 24 or 48 h (Yuan et al, 2015;Li et al, 2016;Wang et al, 2017a). This shows that angelicin has the potential to be effective against multiple cancer cell lines.…”

“…HepG2 cell line (a) Cell viability IC 50 for HepG2: 90 ± 6.565 mM (b) Significant decrease of PI3K/GADPH: ≥ 90 mM (c) Significant decrease of p-AKT/AKT: ≥ 60 mM (d) Upregulation of cleaved caspase 3, caspase 9, Bax, and cytochrome c (e) Downregulation of Bcl-2 2. Huh-7 cell line (a) Cell viability IC 50 for Huh-7: 60 ± 4.256 mM (b) Significant decrease of PI3K/GADPH: ≥ 30 mM (c) Significant decrease in p-AKT/AKT: ≥ 10 mM (d) Upregulation of cleaved caspase 3, caspase 9, Bax, and cytochrome c (e) Downregulation of Bcl-2 In vivo assay (a) Significant decrease in tumor weight: ≥ 50 mg/kg (b) Significant increase of TUNEL-positive cells: ≥ 20 mg/kg (C) Significant decrease in Ki-67 values: ≥ 50 mg/kg (d) Significant decrease in p-VEGFR2 values: ≥ 50 mg/kg (Wang et al, 2017a) Cancer cell lines 1.Human renal carcinoma (Caki) cell line 2. Hepatocellular carcinoma (Sk-hep1) cell line 3.…”

“…Besides seeing a decreased expression of anti-apoptotic Bcl-2 family proteins, increased expression of apoptosis-inducing Bcl-2 family, Bax, was also reported in the treated cell lines. Even the expression levels of cytochrome C was increased dose-dependently when tested in HepG2 and Huh-7 cells (Wang et al, 2017a). An increase in the expression of cytochrome C and Bax had been known to indicate the activation of the intrinsic apoptotic pathway.…”

“…A similar decrease in migration and invasion were also reported in in vitro model of HeLa and SiHa cells by Wang et al (2019b), indicating that such inhibition was not limited to A549 cell lines only but also that angelicin is able to demonstrate anti-invasion and anti-migration properties in both in vitro and in vivo models. Wang et al (2017a) discovered that angular furocoumarin decreases the growth of HepG2induced tumor that was implanted in the back of male BALB/c mice. At the same time, the levels of proliferation marker Ki-67 and phosphorylated vascular endothelial growth factor 2 (p-VEGFR2) were significantly reduced in the tumor tissues.…”

“…Though psoralen has been the subject of many studies due to its phototherapeutic properties, angelicin too has demonstrated multiple effects including anti-cancer, anti-viral, antiinflammatory, anti-microbial, pro-osteogenic and chondrogenic differentiation, and erythroid differentiating properties (Lampronti et al, 2003;Cho et al, 2013;Liu et al, 2013;Wang et al, 2017a;Li et al, 2018). Regarding its anti-viral and erythroid differentiating properties, other studies have also compared angelicin to the common drugs on the market, such as ganciclovir (GCV) and hydroxyurea, and it had was shown that angelicin had almost equal or even better effect as compared to these drugs (Lampronti et al, 2003;Cho et al, 2013).…”