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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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Mechanistic scheme outlining how ACBPs induce apoptosis.
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fig5: Mechanistic scheme outlining how ACBPs induce apoptosis.

Mentions: First, our results showed that ACBPs significantly inhibited HCT116 cell growth in vitro and also enhanced UV-induced cell apoptosis. Western blotting analysis revealed that PARP and p53 were upregulated, whereas Mcl-1 was nearly absent when the cells were subjected to ACBP treatment. PARP is a DNA damage receptor that functions upstream of the p53 signaling pathway. Upregulation of PARP by radiation-induced DNA damage can induce p53, which in turn targets the Mcl-1 binding sites on Bak and/or Bax to release Mcl-1. Free Mcl-1 is susceptible to degradation. However, PUMA did not show any response to the ACBPs. Therefore, we hypothesize that the PARP-p53-Mcl-1 pathway may be involved in ACBP-induced apoptosis in HCT116 cells (Figure 5).


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)

Mechanistic scheme outlining how ACBPs induce apoptosis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4816232&req=5

fig5: Mechanistic scheme outlining how ACBPs induce apoptosis.
Mentions: First, our results showed that ACBPs significantly inhibited HCT116 cell growth in vitro and also enhanced UV-induced cell apoptosis. Western blotting analysis revealed that PARP and p53 were upregulated, whereas Mcl-1 was nearly absent when the cells were subjected to ACBP treatment. PARP is a DNA damage receptor that functions upstream of the p53 signaling pathway. Upregulation of PARP by radiation-induced DNA damage can induce p53, which in turn targets the Mcl-1 binding sites on Bak and/or Bax to release Mcl-1. Free Mcl-1 is susceptible to degradation. However, PUMA did not show any response to the ACBPs. Therefore, we hypothesize that the PARP-p53-Mcl-1 pathway may be involved in ACBP-induced apoptosis in HCT116 cells (Figure 5).

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