Abstract Objective To investigate the possible mechanism through which Artemisinin induced apoptosis in pancreatic cell line.
Methods Column chromatography, thin layer chromatography (TLC) and proton NMR spectroscopy were used to purify Artemisinin. The flowcytometry was employed to detect apoptosis and reactive oxygen species (ROS).
Results The results indicated that 50% inhibiting concentration (IC50 value) for pancreatic cell line (RIN) was 45 μmol/L of Artemisinin. Artemisinin had no cytotoxic effect on the growth of peripheral blood lymphocytes. The mechanism of apoptosis was evaluated by measuring intracellular ROS. It was shown that Artemisinin-induced apoptosis occurred independently of the binding of CD95L to CD95 receptor in the RIN cells. Moreover, Artemisinin, in a dose-dependent manner, could significantly increase the level of ROS.
Conclusion Artemisinin can induce apoptosis in the RIN cells via the generation of ROS and triggering the intrinsic pathway of cell death.
Anticancer activity of botanical compounds in ancient fermented beverages (Review) P.E. McGOVERN1, M. CHRISTOFIDOU-SOLOMIDOU2,3, W. WANG4, F. DUKES2, T. DAVIDSON1 and W.S. EL-DEIRY4
1Biomolecular Archaeology Laboratory, University of Pennsylvania Museum of Archaeology and Anthropology; 2Pulmonary, Allergy and Critical Care Division, 3Center of Excellence in Environmental Toxicology (CEET), and 4Division of Hematology and Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Abstract Humans around the globe probably discovered natural remedies against disease and cancer by trial and error over the millennia. Biomolecular archaeological analyses of ancient organics, especially plants dissolved or decocted as fermented beverages, have begun to reveal the preliterate histories of traditional pharmacopeias, which often date back thousands of years earlier than ancient textual, ethnohistorical, and ethnological evidence. In this new approach to drug discovery, two case studies from ancient Egypt and China illustrate how ancient medicines can be reconstructed from chemical and archaeological data and their active compounds delimited for testing their anticancer and other medicinal effects. Specifically, isoscopoletin from Artemisia argyi, artemisinin from Artemisia annua, and the latter's more easily assimilated semi-synthethic derivative, artesunate, showed the greatest activity in vitro against lung and colon cancers. In vivo tests of these compounds previously unscreened against lung and pancreatic cancers are planned for the future.
Conclusion ..These data show that both artesunate and artemisinin treatments resulted in a concentration-dependent inhibition of cell growth in Lewis lung carcinoma cells, but that artesunate was >30 times as effective ... ...The active compounds detected by the p53 studies included artemisinin, artesunate, borneol, isoscopoletin, and ursolic acid, with inhibition effects on tumor growth ranging in concentration from micromolar to millimolar amounts. Although artesunate, and to a lesser extent artemisinin, are most active against HCT116 colon adenocarcinoma... ...ursolic acid, found in species of thyme, is much more effective against colon cancer under low-oxygen conditions (hypoxia) than normal atmospheric conditions (normoxia). This compound inhibits tumor growth at a concentration of around 50 μM under normoxia; much lower concentrations of 1-10 μM are sufficient to achieve the same result under hypoxia. Tumor cells, especially those which are solid and dense, survive and proliferate under hypoxia. A strategy in anticancer therapy is to counteract thisproperty of tumor cells. It may be hypothesized that the anticancer potency of ursolic acid is related to mechanisms operating under hypoxia... ...Based on these results, we propose in vivo and clinical studies of one derivative compound from A. annua in particular: artesunate. As already known from in vivo mousestudies of other cancers, we plan to test this compound for its clinical efficacy against lung and pancreatic cancer. To date, the effectiveness of artesunate against these specific cancers has not been determined...
Jaceosidin Induces Apoptosis in U87 Glioblastoma Cells through G2/M Phase Arrest Muhammad Khan,1 Bo Yu,2 Azhar Rasul,1 Ali Al Shawi,1 Fei Yi,1 Hong Yang,2 and Tonghui Ma1,3
1Membrane Channel Research Laboratory, Northeast Normal University, Changchun 130024, China 2College of Life Sciences, Liaoning Normal University, Dalian 116029, China 3Second Clinical Hospital, Jilin University, Changchun 130041, China
Abstract Artemisia argyi is a widely used medicinal plant in China. The present study was designed to identify the bioactive constituents with antiglioma activity from leaves of Artemesia argyi. A bioactivity guided approach based on MTT assay for cells growth inhibition led to the isolation of a flavonoid, “jaceosidin” from ethanol extract of leaves of Artemesia argyi. The growth inhibitory effect of jaceosidin was explored using flow cytometry and Western blot studies. Our results showed that jaceosidin exerts growth inhibitory effect by arresting the cells at G2/M phase and induction of apoptosis. Furthermore, our study revealed that induction of apoptosis was associated with cell cycle arrest at G2/M phase, upregulation of p53 and Bax, decrease in mitochondrial membrane potential, release of cytochrome c, and activation of caspase 3. This mitochondrial-caspase-3-dependent apoptosis pathway was confirmed by pretreatment with caspase 3 inhibitor, Ac-DEVD-CHO. Our findings suggested that jaceosidin induces mitochondrial-caspase-3-dependent apoptosis in U87 cells by arresting the cell cycle at G2/M phase.
....In conclusion, our data demonstrated that jaceosidin inhibited the growth of U87 glioblastoma cells and induced apoptosis through cell cycle arrest, upregulation of p53 and Bax, lowering MTP, release of cytochrome c, and cleavage of caspase 3. Thus, jaceosidin could be developed into a novel chemotherapeutic or chemopreventive agent against glioblastoma.
Source : Evidence-Based Complementary and Alternative Medicine Volume 2012 (2012), Article ID 703034, 12 pages doi:10.1155/2012/703034 Link to Full Article
Jaceosidin Induces Apoptosis in Human Ovary Cancer Cells through Mitochondrial Pathway
Wen Lv,1 Xia Sheng,2 Ting Chen,2 Qiang Xu,2 and Xing Xie1 1 The Second Affiliated Hospital, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China 2 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China
We examined the antiproliferation effect of Jaceosidin (4, 5, 7-trihydroxy-3, 6-dimethoxyflavone) isolated from the herb of Artemisia vestita Wall on several human cancer cell lines. Jaceosidin significantly reduced the proliferation of CAOV-3, SKOV-3, HeLa, and PC3 cells in a concentration-dependent manner. A time-dependent inhibition was also observed in CAOV-3 cells by Jaceosidin. By flow cytometric analysis, we found that Jaceosidin treatment resulted in an increased apoptosis in CAOV-3 cells. The cells treated with Jaceosidin exhibited a decreased mitochondrial membrane potential. Jaceosidin also increased the level of cleaved caspase-9 and induced the cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP), while caspase-3 inhibitor Z-DEVD-FMK significantly reversed the proapoptotic effect of Jaceosidin in CAOV-3 cells.Moreover, Jaceosidin elevated the level of cytochrome c in cytosol. These findings suggest that the anticancer effect of Jaceosidin may be contributed by an induction of apoptosis involving cytochrome c release from mitochondria to cytosol.