Extracts of Artocarpus communis Induce Mitochondria-Associated Apoptosis via Pro-oxidative Activity in Human Glioblastoma Cells

Abstract

Glioblastoma multiforme (GBM) is an extremely aggressive and devastating malignant tumor in the central nervous system. Its incidence is increasing and the prognosis is poor. Artocarpin is a natural prenylated flavonoid with various anti-inflammatory and anti-tumor properties. Studies have shown that artocarpin is associated with cell death of primary glioblastoma cells. However, the in vivo effects and the cellular and molecular mechanisms modulating the anticancer activities of artocarpin remain unknown. In this study, we demonstrated that treating the glioblastoma cell lines U87 and U118 cells with artocarpin induced apoptosis. Artocarpin-induced apoptosis is associated with caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage and is mediated by the mitochondrial pathway. This is associated with mitochondrial depolarization, mitochondrial-derived reactive oxidative species (ROS) production, cytochrome c release, Bad and Bax upregulations, and Bcl-2 downregulation. Artocarpin induced NADPH oxidase/ROS generation plays an important role in the mitochondrial pathway activation. Furthermore, we found artocarpin-induced ROS production in mitochondria is associated with Akt- and ERK1/2 activation. After treatment with artocarpin, ROS causes PI3K/Akt/ERK1/2-induced cell death of these tumor cells. These observations were further verified by the results from the implantation of both U87 and U118 cells into in vivo mouse. In conclusion, our findings suggest that artocarpin induces mitochondria-associated apoptosis of glioma cells, suggesting that artocarpine can be a potential chemotherapeutic agent for future GBM treatment.

Anti-Tumor Activity of Cembranoid-Type Diterpenes Isolated from Nicotiana tabacum L.

“…In this study, the morphological changes of HepG2 and SMMC-7721 cells treated with α-CBD were observed under a light microscope and a fluorescence microscope. The results showed that the morphology of hepatocellular carcinoma cells and plasma membrane permeability changed, as observed in previous studies [10,13,15,26].…”

“…As a mode of cell death, apoptosis plays an important role in the origin and development of tumor, and thus, in antitumor drug research [8]. Anti-tumor drugs can inhibit cell growth and induce apoptosis of tumor cells by interfering with their growth, metabolism, proliferation and cell cycle [9,10,11,12]. In addition, there is also accumulating evidence that the efficiency of anti-tumor agents is related to gene regulation and related pathways [13,14,15].…”

Anticancer activity and molecular mechanisms of α‐conidendrin, a polyphenolic compound present in Taxus yunnanensis, on human breast cancer cell lines

“…The cell lysates were incubated with pNA‐conjugated substrates at 37°C for 1 hr (DEVD‐pNA and LEHD‐pNA substrates for caspases‐3 and ‐9, respectively). The amount of pNA released was measured at 405 nm using an ELISA microplate reader (Biotek, H1M, USA; Lee et al, ).…”

Persian Gulf Snail Crude Venom (Conus textile): A Potential Source of Anti-Cancer Therapeutic Agents for Glioblastoma through Mitochondrial-Mediated Apoptosis

“…Caspase-3 activity and absorbance were measured using an ELISA reader (Tecan, Rainbow hermo, Austria) at 405 nm. Three experiments were independently performed for caspase-3 activity determination (Lee et al, 2018).…”