Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo

Abstract

While searching for natural anti-hepatocellular carcinoma (HCC) components in Ailanthus altissima, we discovered that ailanthone had potent antineoplastic activity against HCC. However, the molecular mechanisms underlying the antitumor effect of ailanthone on HCC have not been examined. In this study, the antitumor activity and the underlying mechanisms of ailanthone were evaluated in vitro and in vivo. Mechanistic studies showed that ailanthone induced G0/G1-phase cell cycle arrest, as indicated by decreased expression of cyclins and CDKs and increased expression of p21 and p27. Our results demonstrated that ailanthone triggered DNA damage characterized by activation of the ATM/ATR pathway. Moreover, ailanthone-induced cell death was associated with apoptosis, as evidenced by an increased ratio of cells in the subG1 phase and by PARP cleavage and caspase activation. Ailanthone-induced apoptosis was mitochondrion-mediated and involved the PI3K/AKT signaling pathway in Huh7 cells. In vivo studies demonstrated that ailanthone inhibited the growth and angiogenesis of tumor xenografts without significant secondary adverse effects, indicating its safety for treating HCC. In conclusion, our study is the first to report the efficacy of ailanthone against Huh7 cells and to elucidate its underlying molecular mechanisms. These findings suggest that ailanthone is a potential agent for the treatment of liver cancer.

Scutellaria barbata D. Don (SBD) protects oxygen glucose deprivation/reperfusion-induced injuries of PC12 cells by up-regulating Nrf2

“…The transcription factor NF-E2-related factor 2 (Nrf2) is a member of the cap "n" collar (CNC) subfamily. Nrf2 has been well-known as the major mechanism of cellular defense against oxidative stress that regulates the expression of numerous reactive oxygen species (ROS), showing antioxidative activity [4,5]. When cells suffer from oxidative stress, Nrf2 is activated and further alters the expression of antioxidant response element (ARE)-dependent genes [6,7].…”

Antitumor activity of the Ailanthus altissima bark phytochemical ailanthone against breast cancer MCF‑7 cells

“…Previous research has demonstrated that natural antitumor drugs may serve important roles in the future. A phytochemical study demonstrated the presence of quassinoids in A. altissima and these compounds have been previously demonstrated to exhibit potent antitumor properties (28). To the best of our knowledge, the present study is the first to report that ailanthone isolated from A. altissimahas inhibits proliferation of MCF-7 cells.…”

Deciphering the molecular mechanism and apoptosis underlying the in‐vitro and in‐vivo chemotherapeutic efficacy of vanadium luteolin complex in colon cancer

“…mTOR can also increase the translation of angiogenic factor VEGF, thus take part in the tumour growth. P53 can activate the apoptotic factor capspase-3 which brings about apoptosis by cleaving cellular substances 30. The results of our in-vitro study reveal strong expression of VEGF, mTOR, Akt, and weak expression of p53 and caspase-3 in the untreated HT-29 cancer cells.…”

“…mTOR can also increase the translation of angiogenic factor VEGF, thus take part in the tumour growth. P53 can activate the apoptotic factor capspase‐3 which brings about apoptosis by cleaving cellular substances …”