title: Huachansu mediates cell death in non-Hodgkin's lymphoma by induction of caspase-3 and inhibition of MAP kinase.
abstract: Huachansu (HCS), a hot water extract of the skin glands of Bufo gargarizans (B. melanostictus), has been used extensively in the treatment of various solid tumors in Asia, particularly in China. However, its effect on the growth of malignancies of hematopoietic origin, particularly lymphomas, is limited. Here we investigated the antiproliferative effect and molecular mechanisms of HCS using non-Hodgkin's lymphoma (NHL) Raji, Ramos, and Namalwa cells and the mantle cell lymphoma cells SP53. HCS inhibited proliferation in these cell lines with an IC50 ranging from 3.1 to 25 µl/ml. At a concentration of 25 µl/ml, HCS triggered a sub-G1 arrest in Ramos cells and induced early to late apoptotic cell death. Cleaved caspase-3 was formed in a concentration-dependent manner in Ramos cells following treatment with HCS for 24 h. Intriguingly, when the Ramos cells were treated with the caspase inhibitor ZDEVD, the apoptotic activity of HCS was partially blocked. Furthermore, HCS also blocked the expression of survivin and pRB proteins in a concentration-dependent manner in Ramos cells. Mechanistically, HCS downregulated both the MAPK gene and proteins in Ramos cells. Collectively, our data suggest that HCS is effective in inducing cell death and apoptosis, in part, by activating caspase-3 activity and suppressing MAP kinase in NHL cells.
authors.affiliation: Department of General Oncology, Integrative Medicine Program, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ekem T
authors.initials: ET
authors.lastname: Efuet
authors.affiliation: Department of General Oncology, Integrative Medicine Program, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Ding
authors.affiliation: Department of General Oncology, Integrative Medicine Program, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Cartwright
authors.affiliation: Department of General Oncology, Integrative Medicine Program, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of General Oncology, Integrative Medicine Program, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cohen
authors.affiliation: Department of General Oncology, Integrative Medicine Program, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Peiying
authors.initials: P
authors.lastname: Yang
mesh_terms: D000664:Amphibian Venoms / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism*; D000077022:Survivin
chemical_list: D000664:Amphibian Venoms; D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D004365:Drugs, Chinese Herbal; D051034:Inhibitor of Apoptosis Proteins; D047428:Protein Kinase Inhibitors; D016160:Retinoblastoma Protein; D000077022:Survivin; C545813:huachansu; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3