A Fragrant Environment Containing α-Pinene Suppresses Tumor Growth in Mice by Modulating the Hypothalamus/Sympathetic Nerve/Leptin Axis and Immune System

• Published in: Integrative cancer therapies Vol. 18; p. 1534735419845139
• Main Authors: Kusuhara, Masatoshi, Maruyama, Koji, Ishii, Hidee, Masuda, Yoko, Sakurai, Kazutoshi, Tamai, Eiko, Urakami, Kenichi
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-04-2019; SAGE PUBLICATIONS, INC; SAGE Publishing
• Subjects: Animals; Bicyclic Monoterpenes - pharmacology; Brain-derived neurotrophic factor; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Corticosterone; Enrichment; Epinephrine; Glucose-1-phosphate; Hypothalamus; Hypothalamus - drug effects; Immune system; Immune System - drug effects; Immunology; Leptin; Leptin - metabolism; Lymphocytes B; Lymphocytes T; Male; Melanoma; Mice; Mice, Inbred C57BL; Natural killer cells; Norepinephrine; Spleen; Sympathetic nerves; Sympathetic Nervous System - drug effects; Transplantation; α-Pinene; fragrance; environment; immune cell; α-pinene; cancer; leptin; hypothalamus
• ISSN: 1534-7354; 1552-695X
• DOI: 10.1177/1534735419845139

The environment is thought to affect outcomes in patients with cancer; however, this relationship has not been proven directly. Recently, an enriched environment, as a model of a positive environment, has been shown to suppress tumor growth by lowering leptin production through a pathway involving the hypothalamus/sympathetic nerve/leptin axis. We previously reported that a fragrant environment (FE) containing α-pinene suppressed tumor growth in mice; however, the underlying mechanism has not been elucidated. Accordingly, in this study, we investigated changes in the neuroendocrine and immune systems following exposure to an FE. Mice were exposed to α-pinene (5 h/day) for 4 weeks prior to tumor implantation with murine melanoma cells and 3 weeks after transplantation. In addition to the evaluation of tumor growth, the blood, spleen, and hypothalamus were collected 3 weeks after transplantation, and neuroendocrinological and immunological parameters were measured. Tumor size was ~40% smaller in mice exposed to FE. Moreover, plasma noradrenaline concentrations, which reflected sympathetic nervous activity, tended to increase, and leptin levels were significantly decreased in FE-exposed mice. Levels of stress hormones, such as plasma corticosterone and adrenaline, did not change in the 2 groups. In the hypothalamus, brain-derived neurotrophic factor protein levels and glucose-1-phosphate concentrations were decreased in the FE group. Additionally, numbers of B cells, CD4+ T cells, CD8+ T cells, and natural killer cells increased in the FE-exposed mice. These neurohormonal and immunological changes in the FE-exposed mice suggested that the FE may activate the hypothalamus/sympathetic nerve/leptin axis and immune system, thereby retarding tumor growth.