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Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (1): 51-59.doi: 10.3736/jcim20080111

• Original Experimental Research • Previous Articles     Next Articles

Antitumor activities of kushen flavonoids in vivo and in vitro

Ming-yu Sun1(), Jian Zuo2, Ji-feng Duan2, Jun Han3, Shi-ming Fan2, Wei Zhang2, Li-fang Zhu2, Ming-hui Yao4   

  1. 1. Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    2. Department of Pharmacology, Hutchison Medipharma Ltd, Zhangjiang Hi-Technology Park, Shanghai 201203, China
    3. Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
    4. Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Online:2008-01-20 Published:2008-01-15
  • Contact: SUN Ming-yu

Objective:To explore the antitumor activities of kushen (Sophora flavescens) flavonoids (KS-Fs) in vivo and in vitro.

Methods:Cell proliferation was assayed by using methyl thiazolyl tetrazolium (MTT) method. H22 hepatocellular carcinoma and S180 sarcoma were induced in ICR mice. Lewis lung carcinoma was induced in C57BL/6 mice. H460 and Eca-109 tumor were induced in Balb/c nude mice by injecting 5×10 5 or 5×10 6 tumor cells in the right flank, respectively. 

Results:KS-Fs could inhibit the growth of a variety of human tumor cell lines (A549, SPC-A-1, NCI-H460, etc.) in vitro. The antitumor efficacies were confirmed in the mice models of H22, S180 and Lewis lung tumors and the nude mice models of human H460 and Eca-109 xenografted tumors. The oral or intravenous maximum tolerated dose of KS-Fs was more than 2.8 g/kg or 750 mg/kg respectively, far more than the oral medial lethal dose of kushen alkaloids (≤1.18 g/kg). No adverse reactions were observed.

Conclusion:These results suggest that KS-Fs or kurarinone may be developed as a novel antitumor agent.

Key words: Sophora flavescens, flavones, antineoplastic agents, mice

CLC Number: 

  • R286.91

Figure 1

High-performance liquid chromatograms and chemical structures of compounds in KS-Fs"

Figure 2

Cytotoxicity of marketed preparation of kushen alkaloids and KS-Fs in vitro **P<0.01, vs KS-Fs-treated group."

Table 1

Effects of KS-Fs on tumor and body weights in H22 hepatoma mice ($\bar{x}$±$s_{\bar{x}}$)"

Group n Body weight after tumor excision (g) Tumor weight (g) Inhibition rate (%)
Vehicle control 19 32.04±0.12 2.47±0.03 -
CTX-treated 10 32.23±0.23 0.47±0.02** 81.00
20 mg/kg KS-Fs-treated 10 32.88±0.22 1.40±0.08** 43.40
100 mg/kg KS-Fs-treated 10 32.69±0.18 0.83±0.05** 66.45
500 mg/kg KS-Fs-treated 10 33.77±0.10 0.52±0.02** 78.98

Figure 3

Effects of different doses of KS-Fs on the tumor of H22 hepatoma and S180 sarcoma in mice A: H22 hepatoma; B: S180 sarcoma."

Table 2

Effects of KS-Fs on tumor and body weights in S180 sarcoma mice ($\bar{x}$±$s_{\bar{x}}$)"

Group n Body weight after tumor excision (g) Tumor weight (g) Inhibition rate (%)
Vehicle control 10 29.65±0.51 2.91±0.11 -
CTX-treated 10 27.51±0.14 0.43±0.02** 85.11
60 mg/kg KS-Fs-treated 10 31.73±0.42 0.80±0.08** 72.52
200 mg/kg KS-Fs-treated 10 34.41±0.29* 0.52±0.05** 82.14

Table 3

Effects of KS-Fs on tumor and body weights in Lewis mice with lung carcinoma ($\bar{x}$±$s_{\bar{x}}$)"

Group n Body weight after tumor excision (g) Tumor weight (g) Inhibition rate (%)
Vehicle control 6 19.58±0.19 2.57±0.09 -
CTX-treated 6 18.38±0.07* 0.28±0.01** 88.96
60 mg/kg KS-Fs-treated 6 19.23±0.13 1.53±0.05** 40.26
200 mg/kg KS-Fs-treated 6 19.70±0.15 1.03±0.06** 59.74

Table 4

Effects of KS-Fs on the tumor weight of H460 in xenografted nude mice on the 25th day ($\bar{x}$±$s_{\bar{x}}$)"

Group n RTV Tumor weight (g) Inhibition rate (%)
Vehicle control 8 36.04±4.59 3.19±0.18 -
Cisplatin-treated 5 16.78±1.94** 1.69±0.06* 47.10
200 mg/kg KS-Fs-treated 8 19.24±1.03** 1.70±0.21* 46.80

Figure 4

Effects of KS-Fs or Kur on the relative tumor volume and relative body weight of H460 and Eca-109 xenografted tumors in nude mice *P<0.05, **P<0.01, vs vehicle control group; △P<0.05, △△P<0.01, vs cisplatin-treated group."

Table 5

Effects of KS-Fs or Kur on the tumor weight of Eca-109 in xenografted nude mice on the 22nd day ($\bar{x}$±$s_{\bar{x}}$)"

Group n RTV Tumor weight (g) Inhibition rate (%)
Vehicle control 6 9.08±1.06 0.53±0.04 -
Cisplatin-treated 6 5.25±0.63** 0.27±0.02** 49.81
200 mg/kg Kur-treated 6 5.21±0.63* 0.31±0.02** 41.29
50 mg/kg Kur-treated 6 6.59±0.60 0.50±0.08 4.92
200 mg/kg KS-Fs-treated 6 4.80±0.79* 0.30±0.02* 42.71
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