Cited by 18Tannin, Tannase and Anticancer ActivitiesCancer-related Molecular PathwaysNatural product bioactivities and synthesis

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

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Carriere, Patrick, Kapur, Neeraj, Mir, Hina, Ward, Ashley, Singh, Shailesh·2018·International Journal of Oncology

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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Metadata

Authors
Carriere, P., Kapur, N., Mir, H., Ward, A., & Singh, S.
Affiliations
Morehouse School of Medicine (US)
Corresponding author
Singh, Shailesh
Venue
International Journal of Oncology
Published
2018-07-19
Volume
53
Issue
4
Pages
1442-1454
ISSN
  • 1019-6439 (ISSN-L)
  • 1791-2423
OpenAlex
W2884690170
Cited by
18
References
2
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 4 · 2020: 4 · 2019: 3
FWCI
1.08
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • International Journal of Oncology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • University of Alabama at Birmingham
  • University of Alabama
  • Morehouse School of Medicine
  • National Institutes of Health (CA118638)
  • National Cancer Institute (CA179701, SC1CA180212, CA169716, CA118638, R21CA169716, U01CA179701, CA180212)
Topics
  • Physical Sciences › Chemistry › Organic Chemistry › Tannin, Tannase and Anticancer Activities
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Physical Sciences › Chemistry › Organic Chemistry › Natural product bioactivities and synthesis
Keywords
colon cancer, apoptosis, p53, Bcl-2, Bak, cytochrome c release, cell cycle arrest, 5-fluorouracil, drug synergy, anticancer natural products, DLD-1 cells, HCT116 cells
MeSH terms
Antineoplastic Combined Chemotherapy Protocols, Cell Survival, Colonic Neoplasms, Dose-Response Relationship, Drug, Drug Synergism, Fluorouracil, Humans, Treatment Outcome, Apoptosis, Gene Expression Profiling, Proanthocyanidins, Cell Line, Tumor, Apoptosis Regulatory Proteins, Cell Cycle Checkpoints

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