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Anticancer bioactive peptides suppress human colorectal tumor cell growth and induce apoptosis via modulating the PARP-p53-Mcl-1 signaling pathway.

Su LY, Shi YX, Yan MR, Xi Y, Su XL - Acta Pharmacol. Sin. (2015)

Bottom Line: Treatment of HCT116 cells with ACBPs (35 μg/mL) for 4-6 days significantly inhibited the cell growth.Furthermore, treatment of HCT116 cells with ACBPs (35 μg/mL) for 6-12 h significantly enhanced UV-induced apoptosis, increased the expression of PARP and p53, and decreased the expression of Mcl-1.Administration of ACBPs did not change the body weight of HCT116 xenograft nude mice, but decreased the tumor growth by approximately 43%, and increased the expression of PARP and p53, and decreased the expression of Mcl-1 in xenograft mouse tumor tissues.

View Article: PubMed Central - PubMed

Affiliation: Clinical Medicine Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot 010050, China.

ABSTRACT

Aim: We have reported novel anticancer bioactive peptides (ACBPs) that show tumor-suppressive activities in human gastric cancer, leukemia, nasopharyngeal cancer, and gallbladder cancer. In this study, we investigated the effects of ACBPs on human colorectal cancer and the underlying mechanisms.

Methods: Cell growth and apoptosis of human colorectal tumor cell line HCT116 were measured using cell proliferation assay and flow cytometry, respectively. The expression levels of PARP, p53 and Mcl1A were assessed with Western blotting and immunohistochemistry. For evaluation of the in vivo antitumor activity of ACBPs, HCT116 xenograft nude mice were treated with ACBPs (35 μg/mL, ip) for 10 days.

Results: Treatment of HCT116 cells with ACBPs (35 μg/mL) for 4-6 days significantly inhibited the cell growth. Furthermore, treatment of HCT116 cells with ACBPs (35 μg/mL) for 6-12 h significantly enhanced UV-induced apoptosis, increased the expression of PARP and p53, and decreased the expression of Mcl-1. Administration of ACBPs did not change the body weight of HCT116 xenograft nude mice, but decreased the tumor growth by approximately 43%, and increased the expression of PARP and p53, and decreased the expression of Mcl-1 in xenograft mouse tumor tissues.

Conclusion: Administration of ACBPs inhibits human colorectal tumor cell growth and induces apoptosis in vitro and in vivo through modulating the PARP-p53-Mcl-1 signaling pathway.

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ACBPs suppress tumor growth in vivo. Tumors were harvested after treatment with ACBPs (n=6) and were compared with the control (n=5), with an average inhibitory rate of 43% (A). Body and tumor weight (B), liver weight (C) were measured, the differences between two groups were not statistically significant. Whereas the spleen indices were significantly lower than that in the control (cP<0.01, D). Analysis of tumor apoptosis by flow cytometry in vivo. The tumor cell apoptosis rate was higher in the ACBP-treated group, but the difference was not statistically significant (E). Analysis of tumor cell cycle by flow cytometry in vivo. The proportion of cells that entered the cell cycle was higher in the ACBP-treated group than that in the control group (bP< 0.05, F). HE staining of tumor specimens harvested from in vivo experiments. More tumor cells with apoptotic features were detected in the ACBP-treated group (G).
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fig3: ACBPs suppress tumor growth in vivo. Tumors were harvested after treatment with ACBPs (n=6) and were compared with the control (n=5), with an average inhibitory rate of 43% (A). Body and tumor weight (B), liver weight (C) were measured, the differences between two groups were not statistically significant. Whereas the spleen indices were significantly lower than that in the control (cP<0.01, D). Analysis of tumor apoptosis by flow cytometry in vivo. The tumor cell apoptosis rate was higher in the ACBP-treated group, but the difference was not statistically significant (E). Analysis of tumor cell cycle by flow cytometry in vivo. The proportion of cells that entered the cell cycle was higher in the ACBP-treated group than that in the control group (bP< 0.05, F). HE staining of tumor specimens harvested from in vivo experiments. More tumor cells with apoptotic features were detected in the ACBP-treated group (G).

Mentions: A xenograft nude mouse model was used to test the biological activity of ACBPs in vivo, and mice were inoculated with HCT116 cancer cells. Our results suggest that ACBP treatment improved the survival animals when compared with the control group. The mice in the treatment group were more active and had better appetites, and they resembled normal mice in appearance and body weight. At the end of the experiment, tumors were harvested, and the tumor weights of all groups were examined. Compared with the control group, ACBP treatment significantly suppressed tumor growth by approximately 43% (Figure 3A). The body weights of the ACBP-treated mice were not changed compared to those in the control, whereas the tumor weights of ACBP-treated mice were lower than the tumor weights of the control mice, although the values were not significantly different (Figure 3B). Liver weights and liver indices did not differ between the two groups (Figure 3C). In addition, The spleen weight of the ACBP-treated mice was not changed compared to those in the control, but the spleen weight ratio (%) was significantly lower compared with the controls (P=0.0015; Figure 3D). Cell cycle progression and the apoptosis of the tumor cells in the different groups were examined by flow cytometry. ACBP treatment resulted in a higher incidence of apoptosis compared with the control, but the effects were not significant (Figure 3E). The cell cycle analysis indicated that ACBPs promoted the entry of tumor cells into the S phase of the cell cycle and that the results were statistically significant (P<0.05; Figure 3F). HE staining showed that the tumors in the xenograft mice treated with ACBPs contained more cells that exhibited the characteristics of apoptosis than the controls (Figure 3G).


Anticancer bioactive peptides suppress human colorectal tumor cell growth and induce apoptosis via modulating the PARP-p53-Mcl-1 signaling pathway.

Su LY, Shi YX, Yan MR, Xi Y, Su XL - Acta Pharmacol. Sin. (2015)

ACBPs suppress tumor growth in vivo. Tumors were harvested after treatment with ACBPs (n=6) and were compared with the control (n=5), with an average inhibitory rate of 43% (A). Body and tumor weight (B), liver weight (C) were measured, the differences between two groups were not statistically significant. Whereas the spleen indices were significantly lower than that in the control (cP<0.01, D). Analysis of tumor apoptosis by flow cytometry in vivo. The tumor cell apoptosis rate was higher in the ACBP-treated group, but the difference was not statistically significant (E). Analysis of tumor cell cycle by flow cytometry in vivo. The proportion of cells that entered the cell cycle was higher in the ACBP-treated group than that in the control group (bP< 0.05, F). HE staining of tumor specimens harvested from in vivo experiments. More tumor cells with apoptotic features were detected in the ACBP-treated group (G).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4816232&req=5

fig3: ACBPs suppress tumor growth in vivo. Tumors were harvested after treatment with ACBPs (n=6) and were compared with the control (n=5), with an average inhibitory rate of 43% (A). Body and tumor weight (B), liver weight (C) were measured, the differences between two groups were not statistically significant. Whereas the spleen indices were significantly lower than that in the control (cP<0.01, D). Analysis of tumor apoptosis by flow cytometry in vivo. The tumor cell apoptosis rate was higher in the ACBP-treated group, but the difference was not statistically significant (E). Analysis of tumor cell cycle by flow cytometry in vivo. The proportion of cells that entered the cell cycle was higher in the ACBP-treated group than that in the control group (bP< 0.05, F). HE staining of tumor specimens harvested from in vivo experiments. More tumor cells with apoptotic features were detected in the ACBP-treated group (G).
Mentions: A xenograft nude mouse model was used to test the biological activity of ACBPs in vivo, and mice were inoculated with HCT116 cancer cells. Our results suggest that ACBP treatment improved the survival animals when compared with the control group. The mice in the treatment group were more active and had better appetites, and they resembled normal mice in appearance and body weight. At the end of the experiment, tumors were harvested, and the tumor weights of all groups were examined. Compared with the control group, ACBP treatment significantly suppressed tumor growth by approximately 43% (Figure 3A). The body weights of the ACBP-treated mice were not changed compared to those in the control, whereas the tumor weights of ACBP-treated mice were lower than the tumor weights of the control mice, although the values were not significantly different (Figure 3B). Liver weights and liver indices did not differ between the two groups (Figure 3C). In addition, The spleen weight of the ACBP-treated mice was not changed compared to those in the control, but the spleen weight ratio (%) was significantly lower compared with the controls (P=0.0015; Figure 3D). Cell cycle progression and the apoptosis of the tumor cells in the different groups were examined by flow cytometry. ACBP treatment resulted in a higher incidence of apoptosis compared with the control, but the effects were not significant (Figure 3E). The cell cycle analysis indicated that ACBPs promoted the entry of tumor cells into the S phase of the cell cycle and that the results were statistically significant (P<0.05; Figure 3F). HE staining showed that the tumors in the xenograft mice treated with ACBPs contained more cells that exhibited the characteristics of apoptosis than the controls (Figure 3G).

Bottom Line: Treatment of HCT116 cells with ACBPs (35 μg/mL) for 4-6 days significantly inhibited the cell growth.Furthermore, treatment of HCT116 cells with ACBPs (35 μg/mL) for 6-12 h significantly enhanced UV-induced apoptosis, increased the expression of PARP and p53, and decreased the expression of Mcl-1.Administration of ACBPs did not change the body weight of HCT116 xenograft nude mice, but decreased the tumor growth by approximately 43%, and increased the expression of PARP and p53, and decreased the expression of Mcl-1 in xenograft mouse tumor tissues.

View Article: PubMed Central - PubMed

Affiliation: Clinical Medicine Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot 010050, China.

ABSTRACT

Aim: We have reported novel anticancer bioactive peptides (ACBPs) that show tumor-suppressive activities in human gastric cancer, leukemia, nasopharyngeal cancer, and gallbladder cancer. In this study, we investigated the effects of ACBPs on human colorectal cancer and the underlying mechanisms.

Methods: Cell growth and apoptosis of human colorectal tumor cell line HCT116 were measured using cell proliferation assay and flow cytometry, respectively. The expression levels of PARP, p53 and Mcl1A were assessed with Western blotting and immunohistochemistry. For evaluation of the in vivo antitumor activity of ACBPs, HCT116 xenograft nude mice were treated with ACBPs (35 μg/mL, ip) for 10 days.

Results: Treatment of HCT116 cells with ACBPs (35 μg/mL) for 4-6 days significantly inhibited the cell growth. Furthermore, treatment of HCT116 cells with ACBPs (35 μg/mL) for 6-12 h significantly enhanced UV-induced apoptosis, increased the expression of PARP and p53, and decreased the expression of Mcl-1. Administration of ACBPs did not change the body weight of HCT116 xenograft nude mice, but decreased the tumor growth by approximately 43%, and increased the expression of PARP and p53, and decreased the expression of Mcl-1 in xenograft mouse tumor tissues.

Conclusion: Administration of ACBPs inhibits human colorectal tumor cell growth and induces apoptosis in vitro and in vivo through modulating the PARP-p53-Mcl-1 signaling pathway.

Show MeSH
Related in: MedlinePlus