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

10 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

Funding Information:
This study was supported in part by the funds (CA169716, CA180212, CA118638 and CA179701) from NCI and Morehouse School of Medicine flow cytometry core. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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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