title: Functional Characterisation of Anticancer Activity in the Aqueous Extract of Helicteres angustifolia L. Roots.
abstract: Helicteres angustifolia L. is a shrub that forms a common ingredient of several cancer treatment recipes in traditional medicine system both in China and Laos. In order to investigate molecular mechanisms of its anticancer activity, we prepared aqueous extract of Helicteres angustifolia L. Roots (AQHAR) and performed several in vitro assays using human normal fibroblasts (TIG-3) and osteosarcoma (U2OS). We found that AQHAR caused growth arrest/apoptosis of U2OS cells in a dose-dependent manner. It showed no cytotoxicity to TIG-3 cells at doses up to 50 μg/ml. Biochemical, imaging and cell cycle analyses revealed that it induces ROS signaling and DNA damage response selectively in cancer cells. The latter showed upregulation of p53, p21 and downregulation of Cyclin B1 and phospho-Rb. Furthermore, AQHAR-induced apoptosis was mediated by increase in pro-apoptotic proteins including cleaved PARP, caspases and Bax. Anti-apoptotic protein Bcl-2 showed decrease in AQHAR-treated U2OS cells. In vivo xenograft tumor assays in nude mice revealed dose-dependent suppression of tumor growth and lung metastasis with no toxicity to the animals suggesting that AQHAR could be a potent and safe natural drug for cancer treatment.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.|Drug Discovery and Assets Innovation Laboratory, DAILAB, National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba 305-8565, Japan.|Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Kejuan
authors.initials: K
authors.lastname: Li
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.|Drug Discovery and Assets Innovation Laboratory, DAILAB, National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba 305-8565, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.
authors.forename: Shuang
authors.initials: S
authors.lastname: Sun
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Drug Discovery and Assets Innovation Laboratory, DAILAB, National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba 305-8565, Japan.|School of Integrative and Global Majors, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Sukant
authors.initials: S
authors.lastname: Garg
authors.affiliation: Drug Discovery and Assets Innovation Laboratory, DAILAB, National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba 305-8565, Japan.
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.
authors.forename: Zhongfang
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Gao
authors.affiliation: Drug Discovery and Assets Innovation Laboratory, DAILAB, National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba 305-8565, Japan.|School of Integrative and Global Majors, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D019660:Malvaceae / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C534699:CCNB1 protein, human; C493956:CDKN1A protein, human; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011065:Poly(ADP-ribose) Polymerases