Synergistic Antitumor Effect of a Combination of Paclitaxel and Carboplatin with
                    Nobiletin from Citrus depressa on Non-Small-Cell Lung Cancer Cell Lines

Shinichi Uesato; Hirofumi Yamashita; Ryu Maeda; Yoshiyuki Hirata; Maho Yamamoto; Saki Matsue; Yasuo Nagaoka; Makio Shibano; Masahiko Taniguchi; Kimiye Baba; Motoharu Ju-ichi

doi:10.1055/s-0034-1368321

Planta Medica, Table of Contents

Planta Med 2014; 80(06): 452-457
DOI: 10.1055/s-0034-1368321

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Synergistic Antitumor Effect of a Combination of Paclitaxel and Carboplatin with Nobiletin from Citrus depressa on Non-Small-Cell Lung Cancer Cell Lines

Authors

Shinichi Uesato

¹Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan
Hirofumi Yamashita

¹Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan
Ryu Maeda

¹Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan
Yoshiyuki Hirata

¹Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan
Maho Yamamoto

¹Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan
Saki Matsue

¹Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan
Yasuo Nagaoka

¹Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, Japan
Makio Shibano

²Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan
Masahiko Taniguchi

²Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan
Kimiye Baba

²Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan
Motoharu Ju-ichi

³Faculty of Pharmaceutical Sciences, Mukogawa Womenʼs University, Nishinomiya, Hyogo, Japan

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.

Key words

nobiletin - Citrus depressa - Rutaceae - non-small-cell lung cancer - cancer chemotherapy drug - synergistic effect - A549 cell xenograft

Full Text

References

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