A novel antitumor agent was developed from six kinds of herbs containing Rhus verniciflua (Rv-PEM01). The components were traditionally established for each formula for traditional medicine. The formula was designed to affect antitumor effect as well as maintain host immune functions. First, we investigated the antiproliferative activities of Rv-PEM01 on human and canine tumor cell lines in vitro, and on antitumor effects using BALB/cAJcl-nu/nu mice in vivo. Acute oral toxicity of Rv-PEM01 was also investigated in vivo in ddY mice. Rv-PEM01 exhibited antiproliferative activities against PC-3 (IC50: 0.328 ± 0.081 mg/ml), A549 (IC50: 0.520 ± 0.070 mg/ml), D-17 (IC50: 0.124 ± 0.037 mg/ml) and MRC-5 (IC50: 0.505 ± 0.058 mg/ml) cells. Luteolin 7-β-D-glucopyranoside and apigenin 7-β-D-glucopyranoside were identified as the main active compounds in Rv-PEM01 by HPLC analysis. The single dose toxicity study of Rv-PEM01 did not result in any deaths or abnormalities in daily behavior, body weight gain, or anatomical observations at necropsy. Thus, so we could not calculate the 50% lethal dose (LD50) in mice, but it would be higher than 5.0 g/kg. Treatment with Rv-PEM01 at a dose of 2.5 g/kg tended to show antitumor activities on mice bearing Colon26 tumors compared with the control group. It was concluded that the formula was a safe * Corresponding author. W. Hiruma et al. 40 antitumor agent with no side effects on mouse physiological function as judged by survival and organ weight.

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Different groups of mice were injected s.c. daily with lithium chloride in three doses(0.52, 1.58 and 4.72meg/kg) or with saline for a period of 3 weeks. Lithium administered acutely or chronically did not affect spontaneous locomotor activities. However, methamphetamine-induced hyper-locomotor activities were inhibited in the lithium groups as compared with those in the saline group, while the hyper-locomotor activities induced by tetrabenazine in the nialamide-pretreated animals were reduced to some extent but not significantly by lithium. Tetrabenazine brought about an initial transient increase followed by a decrease of spontaneous locomotor activities in the lithium groups, whereas it induced only a decrease of the activities in the saline group. In addition, jumping and vertical jumping behaviors, which were not observed in the saline group, occurred 30-60 min after tetrabenazine in the lithium groups. These effects of lithium tended to increase with an increase of the doses administered and with a prolongation of its daily administration. The results demonstrate that lithium modifies behavioral responses to methamphetamine and tetrabenazine.

Ganciclovir, 9-(1,3-dihydroxy-2-propoxymethyl)guanine (Fig. 1A), is a nucleoside analogue that has shown activity against viruses of the herpes group, including cytomegalovirus.

The authors declare no con‰ict of interest. a 福岡大学薬学部医薬品情報学教室（〒814 0180 福岡 市城南区七隈 8 19 1） ， b 株式会社紀文食品国際事業室 (〒206 0812 東京都稲城市矢野口 86） ， c サン自然薬研 究所（〒104 0061 東京都中央区銀座 3 12 6）  e-mail: ononob＠fukuoka-u.ac.jp 本総説は，日本薬学会第 132 年会シンポジウム S28 で 発表したものを中心に記述したものである． Cancer is the most common cause of death in Japan. Fundamental and clinical studies on cancer were conducted from the viewpoint of Western medicine so far. However, a sustained complete remission has not been achieved yet. In order to alleviate the side eŠects of anticancer drugs, some traditional herbal medicines (Kampo medicines) have been prescribed to cancer patients. We have been studying on antitumor substances in medicinal herbs and found an antitumor medicinal herb named Rhus vernici‰ua (lacquer, Urushi in Japanese). To investigate the antitumor eŠect in vitro, a plant extract mixture was prepared from six medicinal herbs containing lacquer. The plant extract mixture containing lacquer (Rv-PEM) inhibited the proliferation of several mouse and human tumor cell lines. Rv-PEM had more potent inhibitory eŠect on the proliferation of human leukemia cell lines (MOLT-3, KG-1) than on other tumor cell lines. The IC 50 values of Rv-PEM on MOLT-3 and KG-1 cells were 0.208 and 0.293 mg/mL, respectively. After treating Rv-PEM to the tumor cells, DNA fragmentation and Caspase-3 and -9 activity increased in the treated cells. The mechanisms of the inhibitory proliferation activity of Rv-PEM would involve apoptosis of human leukemia cells (MOLT-3, KG-1, K-562) by the mitochondrial pathway.