title: Beta-asarone induces LoVo colon cancer cell apoptosis by up-regulation of caspases through a mitochondrial pathway in vitro and in vivo.
abstract: Beta-asarone is one of the main bioactive constituents in traditional Chinese medicine Acorus calamu. Previous studies have shown that it has antifungal and anthelmintic activities. However, little is known about its anticancer effects. This study aimed to determine inhibitory effects on LoVo colon cancer cell proliferation and to clarify the underlying mechanisms in vitro and in vivo. Dose-response and time-course anti-proliferation effects were examined by MTT assay. Our results demonstrated that LoVo cell viability showed dose- and time-dependence on β-asarone. We further assessed anti-proliferation effects as β-asarone-induced apoptosis by annexin V-fluorescein isothiocyanate/propidium iodide assay using a flow cytometer and observed characteristic nuclear fragmentation and chromatin condensation of apoptosis by microscopy. Moreover, we found the apoptosis to be induced through the mitochondrial/caspase pathway by decreasing mitochondrial membrane potential (MMP) and reducing the Bcl-2-to-Bax ratio, in addition to activating the caspase-9 and caspase-3 cascades. Additionally, the apoptosis could be inhibited by a pan-caspase inhibitor, carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). When nude mice bearing LoVo tumor xenografts were treated with β-asarone, tumor volumes were reduced and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assays of excised tissue also demonstrated apoptotic changes. Taken together, these findings for the first time provide evidence that β-asarone can suppress the growth of colon cancer and the induced apoptosis is possibly mediated through mitochondria/caspase pathways.
authors.affiliation: Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, Nanjing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zou
authors.forename: Shen-Lin
authors.initials: SL
authors.lastname: Liu
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Bo-Fan
authors.initials: BF
authors.lastname: Ling
authors.forename: Rui-Ping
authors.initials: RP
authors.lastname: Wang
mesh_terms: D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D005343:Fibrinolytic Agents; D012333:RNA, Messenger; C012195:asarone; D020169:Caspases