title: β-elemene inhibits the proliferation of T24 bladder carcinoma cells             through upregulation of the expression of Smad4.
abstract: β-elemene, a non-cytotoxic antitumor reagent, inhibits the growth, proliferation and DNA synthesis of multiple types of malignant cells, resulting in the apoptosis or suppressed vascularization of tumors. β-elemene is also able to enhance the immunogenicity of the tumor cells and ameliorate systematic cellular immunity in the tumor‑bearing body. Moreover, β-elemene has the advantages of high efficiency, safety and low possibility of drug tolerance over other antitumor agents used in antitumor treatment. Therefore, β-elemene has great potential in clinical applications. However, the mechanism of β-elemene antitumor activity is largely unknown. The aim of this study was to investigate whether β-elemene is able to repress the proliferation of T24 bladder carcinoma cells through regulation of the expression of the tumor suppressor gene, Smad4. Results of a methylthiazolyl tetrazolium (MTT) assay indicated that the proliferation of T24 cells was repressed by β-elemene in a time- and concentration‑dependent manner. The lowest concentration of β-elemene to inhibit cell survival by >50% was determined using IC50 software. Microscopic observation also demonstrated the potential of β-elemene to induce the apoptosis of cancer cells. Western blot and RT-PCR analyses revealed that the expression of the Smad4 protein and mRNA was upregulated by treatment with β-elemene. Our results revealed that β-elemene was able to upregulate the expression of Smad4 in tumor cells to inhibit the proliferation of these cells.
authors.affiliation: Department of Urology, The Second Xiangya Hospital of Central                     South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Lu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Luo
authors.forename: Weibin
authors.initials: W
authors.lastname: Qiu
authors.forename: Hu
authors.initials: H
authors.lastname: Han
authors.forename: Xian
authors.initials: X
authors.lastname: Chen
authors.forename: Luoyan
authors.initials: L
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D012717:Sesquiterpenes; D051901:Smad4 Protein; C445979:beta-elemene