Antitumor Effects and Acute Oral Toxicity Studies of a Plant Extract Mixture Containing &lt;i&gt;Rhus verniciflua&lt;/i&gt; and Some Other Herbs

Wataru Hiruma,Nobufumi Ono,Ayaka Miyata,Tsuyoshi Tomita,C A Tony Buffington,Nobuo Yamaguchi,Kohei Suruga,Yasuhiro Komatsu,Kazunari Kadokura,Yoshihiro Sekino,Masahiko Kimura

doi:10.4236/oji.2015.51005

Abstract

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 abnor-malities 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. Treat- ment 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 antitumor agent with no side effects on mouse physiological function as judged by survival and organ weight.

Highlights

Many phytochemicals from fruits, vegetables, and herbs which have antitumor activities may represent promising therapeutic and prophylactic treatment approaches against different types of cancers
We recently reported that two novel urushiol derivatives, 1,2-dihydroxyphenyl-3-pentadeca-7′(E),9′(Z),11′(Z)-trien14′-ol and 1,2-dihydroxyphenyl-3-pentadeca-8′(Z),10′(E),12′(E)-trien-14′-ol, isolated from the extract of leaves of R. verniciflua for the first time, showed inhibition of HIV-1 reverse transcriptase (RT) [10]
We reported the anti-cell-proliferative activities of a plant extract mixture from six kinds of herbs containing R. verniciflua (Rv-PEM01) in vitro

Summary

Introduction

Many phytochemicals from fruits, vegetables, and herbs which have antitumor activities may represent promising therapeutic and prophylactic treatment approaches against different types of cancers. The effects of phytochemicals on inhibition of tumor growth are well demonstrated both in vitro and in vivo. Many of these compounds, such as vinca alkaloids, have been reported to kill cancer cells [1]. Many herbal extracts or their components have been reported to induce apoptosis in cancer cells [4], so apoptosis-inducing activity of anticancer herbs may play an important role in tumor suppression. Several Kampo (traditional Chinese or Japanese herbal) medicines, such as Keishi-ka-kei-to, Juzen-taiho-to, Shimotsu-to, Unsei-in, Hochu-ekki-to, Shosaiko-to and Shichimotsu-koka-to, have been reported to exhibit an antimetastatic effect, and among them, Keishi-ka-kei-to, Juzen-taiho-to, Shosaiko-to and Shichimotsu-koka-to exert antiproliferative activity on cancer cell lines [5]. THL is reported to have potent immunomodulatory effects [6] and antiproliferative activity [7]

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