[Frontiers in Bioscience S4, 1539-1546, June 1, 2012]

Cytochrome P450 in non-small cell lung cancer related to exogenous chemical metabolism

Tsunehiro Oyama1, 2, Hidetaka Uramoto3, Norio Kagawa4, Takashi Yoshimatsu5, Toshihiro Osaki6, Ryoichi Nakanishi7, Hisao Nagaya2, Kazuhiro Kaneko8, Manabu Muto9, Toshihiro Kawamoto10, Fumihiro Tanaka 3, Akinobu Gotoh 2

1Medical center for respiratory disease, Nishinihon Hospital, 3-20-1, Hattanda, Kumamoto, 861-8034, Japan, 2Laboratory of Cell and Gene Therapy, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501 Japan, 3Second Department of Surgery, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan, 4 Global COE, Nagoya University School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan,5Department of Thoracic Surgery, Fukuoka-Wajiro Hospital, 2-2-75, Wajirogaoka, Higashi-ku, Fukuoka, 811-0213, Japan, 6Department of Chest Surgery, Iizuka Hospital, 3-83, Yoshio-machi, Iizuka, 820-8505, Japan, 7Department of Thoracic Surgery, Shin-Kokura Hospital, Federation of National Public Service Personnel Mutual Aid Associations, 1-3-1, Kanada, Kokurakita-ku, Kitakyushu, 803-8505, Japan, 8Department of Gastroenterology and GI Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan 9Department of Gastroenterology and Hepatology, Graduate School of Medicine, 54, Shougoin Kawahara-cho, Sakyou-ku, Kyoto University, Kyoto, 606-8507, Japan, 10Department of Environmental Health, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Expression of CYPs involved in drug metabolism in non-small cell lung cancer
4. Expression of CYP19 (aromatase) in lung cancer
5. Involvement of vitamin D3 and CYP24A1 in lung cancer
6. Perspectives
7. Acknowledgements
8. References

1. ABSTRACT

The occurrence of lung cancer is associated with smoking, which exposes smokers to a series of carcinogenic chemicals. CYP (cytochrome P450) usually metabolizes carcinogens to their inactive derivatives, but occasionally convert the chemicals to more potent carcinogens. In addition to the metabolism of carcinogenic compounds, CYP also participates in the activation and/or inactivation of anti-carcinogenic agents, suggesting that the local CYP expression in lung cancer and surrounding tissues could be an important determinant of efficacy of anticancer drugs. Furthermore, CYP19 (aromatase), estrogen synthase P450, expressed in more than 80% of non-small cell lung cancers. It suggests an association between estrogens and cancer development, which makes aromatase an attractive therapeutic target for the treatment of lung cancer. 1a ,25-Dihydroxyvitamin D3 has an inhibitory effect on the proliferation of cancer tissues, and is converted to its inactive 24-hydroxylated derivatives by CYP24, which is frequently expressed in lung cancer tissues. Therefore, understanding the CYP expression in tumor tissues is important in developing better therapies for lung cancer, and may lead us to standardized, "tailor-made" therapies for individuals.