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

Patrick P. Carriere, Neeraj Kapur, Hina Mir, Ashley B. Ward, Shailesh Singh

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Colon cancer patients receiving chemotherapy continue to be burdened with therapeutic failure and adverse sideeffects,yieldinganeedtodevelopmoreeffectivetreatments. 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.

Original languageEnglish
Pages (from-to)1442-1454
Number of pages13
JournalInternational Journal of Oncology
Volume53
Issue number4
DOIs
StatePublished - Oct 2018

Bibliographical note

Publisher Copyright:
© 2018 Spandidos Publications. All rights reserved.

Keywords

  • 5-fluorouracil
  • Apoptosis
  • Cinnamtannin B-1
  • Colon cancer
  • Proanthocyanidins
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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