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

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 signifi-cantly 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.

Recruitment of Mesenchymal Stem Cells to Damaged Sites by Plant-Derived Components

“…Cinnamtannin B-1 is a proanthocyanidin found in specific plants such as Cinnamomum zeylanicum (Sánchez-Rubio et al, 2018). Cinnamtannin B-1 exhibits anti-inflammatory, anti-oxidant and anti-thrombotic properties (López et al, 2008), and also protects neurons from ischemia/reperfusion-induced dysfunction (Chi et al, 2013), while inhibiting survival of cancer cells (Carriere et al, 2018), and protecting pancreatic acinar cells during pancreatitis (Rivera-Barreno et al, 2010).…”

Cinnamtannin B-1 Inhibits the Progression of Osteosarcoma by Regulating the miR-1281/PPIF Axis

“…However, the exact mechanism by which it increases miR-1281 expression has not been fully understood yet. Since p53 and NF-kappa B were reported as downstream signaling molecules modulated by CBT-1, 9,10,23) playing established roles in p53 and NF-kappa B-involved inflammatory pathway for regulating the miRNA network, 24,25) we believed that CBT-1 might modulate miR-1281 through these mediators. Subsequently, we also analyzed the downstream targets of the miR-1281 using bioinformatics analysis.…”

“…9) Moreover, CTB-1 was useful in the treatment of colon cancer, where it inhibited disease development through the regulation of the p53 pathway. 10) However, the involvement of CTB-1 in OS proliferation and metastasis remains unclear. Therefore, our study aimed to investigate the biological functions and potential underlying mechanisms of CTB-1 in OS.…”

Natural flavonoids for the prevention of colon cancer: A comprehensive review of preclinical and clinical studies

“…Moreover, it is indicated that resveratrol combination with piceatannol could lead to increased expression of programmed cell death ligand 1, thus decreasing tumor survival in CRC (Lucas, Hsieh, Halicka, Darzynkiewicz, & Wu, 2018). 5-FU potency in CRC could be enhanced by other flavonoids, for example, cinnamtannin B-1 which modulate cell survival pathways such as p53 which are involved in apoptosis (Carriere, Kapur, Mir, Ward, & Singh, 2018).…”