Open Access

Cinnamtannin B-1 inhibits cell survival molecules and induces apoptosis in colon cancer

  • Authors:
    • Patrick P. Carriere
    • Neeraj Kapur
    • Hina Mir
    • Ashley B. Ward
    • Shailesh Singh
  • View Affiliations

  • Published online on: July 19, 2018     https://doi.org/10.3892/ijo.2018.4489
  • Pages: 1442-1454
  • Copyright: © Carriere et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colon cancer patients receiving chemotherapy continue to be burdened with therapeutic failure and adverse side effects, yielding a need to develop more effective treatments. The present study investigates Cinnamtannin B-1 (CTB-1) as a potential low-toxicity therapeutic alternative for colon cancer. CTB-1-treated DLD-1, COLO 201 and HCT-116 (WT p53 and p53 null) colon cancer cells and CCD 841 CoN normal colon epithelial cells were assessed for changes in survival using MTT assay. The effects of CTB-1 on cell cycle progression and the apoptosis of colon cancer cells were measured using flow cytometry and/or immunofluorescence. The expression profiles of cell survival molecules, particularly apoptotic proteins, in the colon cancer cells were evaluated following CTB-1 treatment via antibody array, then validated by western blot analysis. Additionally, the potential synergy between CTB-1 and 5-fluorouracil (5-FU), a conventional chemotherapeutic agent used in the treatment of colon cancer, against colon cancer cells was assessed using MTT assay and Calcusyn software. The results revealed that CTB-1 significantly decreased the survival of the DLD-1, COLO 201 and HCT-116 cells in a time and/or dose-dependent manner, with minimal cytotoxicity to normal colon cells. CTB-1 treatment was shown to induce cell cycle arrest and apoptosis of DLD-1 and COLO 201 cells. Of note, CTB-1 modulated the expression of several cell survival molecules, which tend to be deregulated in colon cancer, including p53, a key transcription factor involved in apoptosis. The downstream regulation of Bcl-2 and Bak expression, as well as cytochrome c release into the cytosol, was also observed following CTB-1 treatment. Furthermore, CTB-1 was shown to significantly enhance the potency of 5-FU via a synergistic drug interaction. This study reveals for the first time, to the best of our knowledge, the ability of CTB-1 to decrease the survival of colon cancer cells through pro-apoptotic mechanisms and display synergy with conventional chemotherapy, demonstrating the potential therapeutic benefit of CTB-1 in colon cancer.
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October 2018
Volume 53 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
APA
Carriere, P.P., Kapur, N., Mir, H., Ward, A.B., & Singh, S. (2018). Cinnamtannin B-1 inhibits cell survival molecules and induces apoptosis in colon cancer. International Journal of Oncology, 53, 1442-1454. https://doi.org/10.3892/ijo.2018.4489
MLA
Carriere, P. P., Kapur, N., Mir, H., Ward, A. B., Singh, S."Cinnamtannin B-1 inhibits cell survival molecules and induces apoptosis in colon cancer". International Journal of Oncology 53.4 (2018): 1442-1454.
Chicago
Carriere, P. P., Kapur, N., Mir, H., Ward, A. B., Singh, S."Cinnamtannin B-1 inhibits cell survival molecules and induces apoptosis in colon cancer". International Journal of Oncology 53, no. 4 (2018): 1442-1454. https://doi.org/10.3892/ijo.2018.4489