Abstract 4713: A Kampo (Japanese herbal) medicine Juzentaihoto may suppress the expression of indoleamine 2, 3-dioxygenase on macrophages and prolong the survival of transgenic mice bearing lens-epithelial cell carcinoma.
Authors: Nakamura Takafumi 
Published: August 2014

Kampo medicine (the traditional Chinese medicine) is a pharmaceutical grade multi-herbal medicine widely used for immunocompromized patient in Japan. Juzentaihoto is a well known Kampo medicine that comprises 10 different herbs. The effect of a Kampo medicine Juzentaihoto on survival of tumor-bearing mice was measured in this study.

We previously reported αT3 transgenic mice carrying αA-SV40Tag transgene (αA denotes murine αA-crystallin promoter). The αT3 mice carry a single copy of transgene, which have been generated from αA-loxP-SV40Tag/Ella-cre double transgenics. The αT3 lens tumors show multi-step carcinogenesis(J Cancer Res Clin Oncol 135:1521-1532 2009). At birth the αT3 lens tumors demonstrate moderate∼severe dysplasia, and in 2-3 month-old they become carcinoma in situ and start to invade lens capsule, and in 4-6 month-old they proliferate in the eyeball and finally they enlarge and destroy eyeballs. The αT3 lens tumor is growing very slow and finally invading and destroying surrounding brain tissue, and some of the αT3 lens tumor, metastasizing to cervical lymph node and lung. Finally αT3 mice died due to cancer cachexia. Carcinogenesis of the αT3 lens tumor induced by SV40 T antigens is pathologically very similar to uterine cervical cancer, which is induced by high-risk human papillomavirus E6 and E7 oncoprotein(Cancer Lett 179:165-173 2002, Oncol Rep 12:253-258 2004, Oncogene 25:3670-3679 2006). We also reported that expression of indoleamine 2, 3-dioxygenase(IDO)increases as tumors progress from carcinoma in situ to microinvasive and invasive cancer, and that tumor associated macrophages(TAMs) localized at the invasive front express IDO in patients with cervical cancer(Cancer Sci 98:874-881 2007).

In this study, the αT3 mice were fed bait containing 1.5% Juzentaihoto for more than one year and the survival rate was compared with the untreated control. We also analyzed various biological activities, such as phagocytosis, IL-10 and IL-12 induction, especially IDO-expression on macrophages.

Oral administration of Juzentaihoto activated peritoneal exudate macrophages and recruited the IDO-negative macrophages. The number of TAMs also increased as compared with the untreated control. These results suggest that oral administration of Juzentaihoto affect macrophage expression of IDO, possibly through a mechanism mediated by the activation of M1 macrophages and modulate local innate immunity.

Citation Format: Takafumi Nakamura. A Kampo (Japanese herbal) medicine Juzentaihoto may suppress the expression of indoleamine 2, 3-dioxygenase on macrophages and prolong the survival of transgenic mice bearing lens-epithelial cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4713. doi:10.1158/1538-7445.AM2013-4713