Beneficial effects of 20(S)-protopanaxadiol on antitumor activity and toxicity of cyclophosphamide in tumor-bearing mice

Abstract

20(S)-protopanaxadiol (PPD) is an extract of Panax quinquefolius L. The aim of this study was to investigate the effect of PPD on the antitumor activity and toxicity of cyclophosphamide (CTX) in tumor-bearing mice. C57BL/6 mice bearing Lewis lung carcinoma cells were treated with PPD (50 mg/kg) alone, CTX (20 mg/kg) alone or PPD (50 mg/kg) in combination with CTX (20 mg/kg), respectively. The results showed that PPD alone has no significant antitumor activity but synergistically enhanced the antitumor activity of CTX. PPD significantly increased the peripheral white blood cell count, bone marrow cell count, interleukin-2 and interferon-γ in CTX-treated tumor-bearing mice. The lowered levels of spleen index, splenocyte proliferation and natural killer cell activity in tumor-bearing mice following CTX treatment were also increased by PPD administration. PPD may be a beneficial supplement during CTX chemotherapy for enhancing the antitumor efficacy and reducing the toxicity of CTX.

Keywords: 20(S)-protopanaxadiol; cyclophosphamide; spleen index; white blood cell count.

Figure 1.

Chemical structure of 20(S)-protopanaxadiol.

Figure 2.

(A) Effects of PPD on antitumor activity in CTX-treated tumor-bearing mice. Data are expressed as the mean ± SD (n=10). Statistical significance was determined using ANOVA, followed by Student-Newman-Keuls tests. ^**P<0.01 compared with the control group; ^#P<0.05 compared with the CTX group. (B) Images of excised tumors at the time of sacrifice from the subcutaneous tumor-bearing mice after PPD, CTX or PPD in combination with CTX treatment. PPD, 20(S)-protopanaxadiol; CTX, cyclophosphamide; ANOVA, analysis of variance.

Figure 3.

Effects of PPD on (A) peripheral white blood cell and (B) bone marrow cell counts in CTX-treated tumor-bearing mice. Data are expressed as the mean ± SD (n=10). Statistical significances were determined using ANOVA, followed by Student-Newman-Keuls tests. ^**P<0.01 compared with the control group; ^#P<0.05 compared with the CTX group. PPD, 20(S)-protopanaxadiol; CTX, cyclophosphamide; ANOVA, analysis of variance.

Figure 4.

Effects of PPD on (A) spleen index and (B) splenocyte proliferation in CTX-treated tumor-bearing mice. Data are expressed as the mean ± SD (n=10). Statistical significances were determined using ANOVA, followed by Student-Newman-Keuls tests. ^**P<0.01 compared with the control group; ^#P<0.05 compared with the CTX group. PPD, 20(S)-protopanaxadiol; CTX, cyclophosphamide; ANOVA, analysis of variance.

Figure 5.

Effects of PPD on NK cell activity in CTX-treated tumor-bearing mice. Data were expressed as the mean ± SD (n=10). Statistical significances were determined using ANOVA, followed by Student-Newman-Keuls tests. ^**P<0.01 compared with the control group; ^#P<0.05 compared with the CTX group. PPD, 20(S)-protopanaxadiol; CTX, cyclophosphamide; ANOVA, analysis of variance.

Figure 6.

Effects of PPD on the levels of (A) IL-2 and (B) INF-γ in CTX-treated tumor-bearing mice. Data were expressed as the mean ± SD (n=10). Statistical significances were determined using ANOVA, followed by Student-Newman-Keuls tests. ^**P<0.01 compared with the control group; ^#P<0.05 compared with the CTX group. PPD, 20(S)-protopanaxadiol; CTX, cyclophosphamide; IL-2, interleukin-2; INF-γ; interferon-γ ANOVA, analysis of variance.