Berberine enhances tumor necrosis factor‑related apoptosis‑inducing ligand‑mediated apoptosis in breast cancer

  • Authors:
    • Alaa Refaat
    • Sherif Abdelhamed
    • Hideo Yagita
    • Hiroki Inoue
    • Satoru Yokoyama
    • Yoshihiro Hayakawa
    • Ikuo Saiki
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  • Published online on: July 1, 2013     https://doi.org/10.3892/ol.2013.1434
  • Pages: 840-844
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Abstract

Berberine (BBR) has been used for the treatment of bacterial and fungal infections and also for cancer‑associated symptoms such as diarrhea. Furthermore, it has been reported that BBR may have direct antitumor effects. Although evidence supports the theory that tumor necrosis factor (TNF)‑related apoptosis‑inducing ligand (TRAIL) is a promising candidate for treating cancer, its usage may be limited due to the resistance to the TRAIL‑induced apoptosis of cancer cells. In the present study, the effect of BBR on TRAIL‑induced antitumor effects was investigated in vitro using recombinant TRAIL and in vivo using a 4T1 murine breast cancer model in combination with anti‑DR5 (death‑inducing TRAIL receptor) monoclonal antibody therapy. BBR sensitized human breast cancer cell lines to TRAIL‑mediated apoptosis in vitro. The combination of BBR and recombinant TRAIL significantly activated caspase‑3 and PARP cleavage in TRAIL‑resistant MDA‑MB‑468 cells. Furthermore, BBR in combination with TRAIL more effectively induced apoptosis compared with coptisine (COP), which is structurally related to BBR. In a murine 4T1 breast cancer model, BBR treatment enhanced the efficacy of anti‑DR5 antibody therapy against primary tumor growth and lung metastasis. Thus, BBR may become a new adjuvant for overcoming the resistance of cancer cells to TRAIL/DR5‑mediated therapy.
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September 2013
Volume 6 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Refaat A, Abdelhamed S, Yagita H, Inoue H, Yokoyama S, Hayakawa Y and Saiki I: Berberine enhances tumor necrosis factor‑related apoptosis‑inducing ligand‑mediated apoptosis in breast cancer. Oncol Lett 6: 840-844, 2013
APA
Refaat, A., Abdelhamed, S., Yagita, H., Inoue, H., Yokoyama, S., Hayakawa, Y., & Saiki, I. (2013). Berberine enhances tumor necrosis factor‑related apoptosis‑inducing ligand‑mediated apoptosis in breast cancer. Oncology Letters, 6, 840-844. https://doi.org/10.3892/ol.2013.1434
MLA
Refaat, A., Abdelhamed, S., Yagita, H., Inoue, H., Yokoyama, S., Hayakawa, Y., Saiki, I."Berberine enhances tumor necrosis factor‑related apoptosis‑inducing ligand‑mediated apoptosis in breast cancer". Oncology Letters 6.3 (2013): 840-844.
Chicago
Refaat, A., Abdelhamed, S., Yagita, H., Inoue, H., Yokoyama, S., Hayakawa, Y., Saiki, I."Berberine enhances tumor necrosis factor‑related apoptosis‑inducing ligand‑mediated apoptosis in breast cancer". Oncology Letters 6, no. 3 (2013): 840-844. https://doi.org/10.3892/ol.2013.1434