title: Synergistic antitumor effect of a combination of paclitaxel and carboplatin with nobiletin from Citrus depressa on non-small-cell lung cancer cell lines.
abstract: Non-small-cell lung carcinomas do not sufficiently respond to cancer chemotherapeutic drugs. Combination effects of cancer chemotherapy drugs (paclitaxel and carboplatin) with nobiletin or powdered Shiikuwasha extract from Citrus depressa were examined by isobologram and combination index analyses. It was demonstrated that the combination generated a synergistic inhibitory effect against the proliferation of the human non-small-cell lung carcinoma cell lines A549 and H460 and that of the two chemotherapy drugs, paclitaxel was responsible for this synergistic effect. Furthermore, the percentage of apoptotic cells was decreased with increasing rates of nobiletin to paclitaxel and carboplatin. These findings were considered to be attributed to the ability of nobiletin to regulate cells in the G1 phase, which escaped cell death initiated by paclitaxel and carboplatin. An antitumor activity assay showed that this combination significantly suppressed the growth of subcutaneous A549 tumor xenografts in nude mice.
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uesato
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Maeda
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Matsue
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Nagaoka
authors.affiliation: Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Makio
authors.initials: M
authors.lastname: Shibano
authors.affiliation: Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Kimiye
authors.initials: K
authors.lastname: Baba
authors.affiliation: Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Motoharu
authors.initials: M
authors.lastname: Ju-ichi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis; D016190:Carboplatin / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002957:Citrus / Q000737:chemistry*; D004357:Drug Synergism; D005260:Female; D047309:Flavones / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008807:Mice, Inbred BALB C; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; D010936:Plant Extracts; D016190:Carboplatin; C008661:nobiletin; D017239:Paclitaxel