Preventive effect of Dioscorea japonica on squamous cell carcinoma of mouse skin involving down-regulation of prostaglandin E2 synthetic pathway

Izumi Tsukayama; Keisuke Toda; Yasunori Takeda; Takuto Mega; Mitsuki Tanaka; Yuki Kawakami; Yoshitaka Takahashi; Masumi Kimoto; Kei Yamamoto; Yoshimi Miki; Makoto Murakami; Toshiko Suzuki-Yamamoto

doi:10.3164/jcbn.17-54

Preventive effect of Dioscorea japonica on squamous cell carcinoma of mouse skin involving down-regulation of prostaglandin E₂ synthetic pathway

J Clin Biochem Nutr. 2018 Mar;62(2):139-147. doi: 10.3164/jcbn.17-54. Epub 2018 Jan 12.

Authors

Izumi Tsukayama¹, Keisuke Toda¹, Yasunori Takeda¹, Takuto Mega¹, Mitsuki Tanaka¹, Yuki Kawakami¹, Yoshitaka Takahashi¹, Masumi Kimoto¹, Kei Yamamoto^{2

3

4}, Yoshimi Miki^{2

5}, Makoto Murakami^{2

5

6}, Toshiko Suzuki-Yamamoto¹

Affiliations

¹ Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
² Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan.
³ Graduate School of Technology, Industrial and Social Science, Tokushima University, Minami-jyosanjima, Tokushima 770-8513, Japan.
⁴ PRIME, Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo 100-0004, Japan.
⁵ Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
⁶ AMED-CREST, Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo 100-0004, Japan.

Abstract

Hyperproduced prostaglandin E₂ by cyclooxygenase-2 and microsomal prostaglandin E synthase-1 evokes several pathophysiological responses such as inflammation and carcinogenesis. Our recent study demonstrated that Dioscorea japonica extract suppressed the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 and induced apoptosis in lung carcinoma A549 cells. In the present study, we investigated the effects of Dioscorea japonica on squamous cell carcinoma of mouse skin. Dioscorea japonica feeding and Dioscorea japonica extract topical application suppressed the expression of cyclooxygenase-2, microsomal prostaglandin E synthase-1, interleukin-1β and interleukin-6 and inhibited tumor formation, hyperplasia and inflammatory cell infiltration. Immunohistochemical analyses showed the immunoreactivities of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in tumor keratinocytes and stronger immunoreactivities of cyclooxygenase-2 and hematopoietic prostaglandin D synthase in epidermal dendritic cells (Langerhans cells). Treatment with Dioscorea japonica decreased the immunoreactivity of cyclooxygenase-2 and microsomal prostaglandin E synthase-1. These results indicate that Dioscorea japonica may have inhibitory effects on inflammation and carcinogenesis via suppression of the prostaglandin E₂ synthetic pathway.

Keywords: carcinogenesis; inflammation; prostaglandin E2; skin cancer; wild yam.