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.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.

References

1 

Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, et al: SEER Cancer Statistics Review, 1975–2013. National Cancer Institute; Bethesda, MD: 2016

3 

Braun MS and Seymour MT: Balancing the efficacy and toxicity of chemotherapy in colorectal cancer. Ther Adv Med Oncol. 3:43–52. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Hu CY, Chan W, Delclos GP and Du XL: Adjuvant chemotherapy and risk of gastrointestinal, hematologic, and cardiac toxicities in elderly patients with stage III colon cancer. Am J Clin Oncol. 35:228–236. 2012. View Article : Google Scholar

5 

Nadeem H, Jayakrishnan TT, Gamblin TC and Turaga K: Cost differential among systemic therapies for colon cancer. Ann Surg Oncol. 21:S832014.

6 

Liu CJ, Lin JK, Chen W-S, Lin TC, Yang SH, Jiang JK, Chang SC, Lan YT, Yen CC, Tzeng CH, et al: The efficacy of chemotherapy in patients with high-grade metastatic colon cancer. Hepatogastroenterology. 58:1495–1501. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Engstrom PF, Arnoletti JP, Benson AB III, Chen YJ, Choti MA, Cooper HS, Covey A, Dilawari RA, Early DS, Enzinger PC, et al National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Colon cancer. J Natl Compr Canc Netw. 7:778–831. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Patel BB, Sengupta R, Qazi S, Vachhani H, Yu Y, Rishi AK and Majumdar AP: Curcumin enhances the effects of 5-fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF-1R. Int J Cancer. 122:267–273. 2008. View Article : Google Scholar

9 

Patel BB, Gupta D, Elliott AA, Sengupta V, Yu Y and Majumdar AP: Curcumin targets FOLFOX-surviving colon cancer cells via inhibition of EGFRs and IGF-1R. Anticancer Res. 30:319–325. 2010.PubMed/NCBI

10 

Chen WT-L, Yang T-S, Chen H-C, Chen HH, Chiang HC, Lin TC, Yeh CH, Ke TW, Chen JS, Hsiao KH, et al: Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil-based chemotherapy in colorectal cancer. Nutr Res. 34:585–594. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Amin ARMR, Kucuk O, Khuri FR and Shin DM: Perspectives for cancer prevention with natural compounds. J Clin Oncol. 27:2712–2725. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Plumb GW, De Pascual-Teresa S, Santos-Buelga C, Cheynier V and Williamson G: Antioxidant properties of catechins and proanthocyanidins: Effect of polymerisation, galloylation and glycosylation. Free Radic Res. 29:351–358. 1998. View Article : Google Scholar : PubMed/NCBI

13 

Santos-Buelga C and Scalbert A: Proanthocyanidins and tannin-like compounds - nature, occurrence, dietary intake and effects on nutrition and health. J Sci Food Agric. 80:1094–1117. 2000. View Article : Google Scholar

14 

Prasad R, Vaid M and Katiyar SK: Grape proanthocyanidin inhibit pancreatic cancer cell growth in vitro and in vivo through induction of apoptosis and by targeting the PI3K/Akt pathway. PLoS One. 7:e430642012. View Article : Google Scholar : PubMed/NCBI

15 

Sharma SD, Meeran SM and Katiyar SK: Proanthocyanidins inhibit in vitro and in vivo growth of human non-small cell lung cancer cells by inhibiting the prostaglandin E(2) and prostaglandin E(2) receptors. Mol Cancer Ther. 9:569–580. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Singh T, Sharma SD and Katiyar SK: Grape proanthocyanidins induce apoptosis by loss of mitochondrial membrane potential of human non-small cell lung cancer cells in vitro and in vivo. PLoS One. 6:e274442011. View Article : Google Scholar : PubMed/NCBI

17 

Nomoto H, Iigo M, Hamada H, Kojima S and Tsuda H: Chemoprevention of colorectal cancer by grape seed proanthocyanidin is accompanied by a decrease in proliferation and increase in apoptosis. Nutr Cancer. 49:81–88. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Chen Q, Liu X-FF and Zheng P-SS: Grape seed proanthocyanidins (GSPs) inhibit the growth of cervical cancer by inducing apoptosis mediated by the mitochondrial pathway. PLoS One. 9:e1070452014. View Article : Google Scholar : PubMed/NCBI

19 

Vaid M, Singh T and Katiyar SK: Grape seed proanthocyanidins inhibit melanoma cell invasiveness by reduction of PGE2 synthesis and reversal of epithelial-to-mesenchymal transition. PLoS One. 6:e215392011. View Article : Google Scholar : PubMed/NCBI

20 

Engelbrecht AM, Mattheyse M, Ellis B, Loos B, Thomas M, Smith R, Peters S, Smith C and Myburgh K: Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell line. Cancer Lett. 258:144–153. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Nandakumar V, Singh T and Katiyar SK: Multi-targeted prevention and therapy of cancer by proanthocyanidins. Cancer Lett. 269:378–387. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Ting-Ting L, Tong L, Yu-Cong Z and Ke-Yuan Z: Inhibitive effect of proanthocyanidins on cyclooxygenase-2 expression in A549 cells induced by cytokine interleukin-1 beta. J Shanghai Jiaotong Univ. 17:500–504. 2012. View Article : Google Scholar

23 

Jayaprakasha GK, Ohnishi-Kameyama M, Ono H, Yoshida M and Jaganmohan Rao L: Phenolic constituents in the fruits of Cinnamomum zeylanicum and their antioxidant activity. J Agric Food Chem. 54:1672–1679. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Dall'Acqua S, Cervellati R, Speroni E, Costa S, Guerra MC, Stella L, Greco E and Innocenti G: Phytochemical composition and antioxidant activity of Laurus nobilis L. leaf infusion J Med Food. 12:869–876. 2009. View Article : Google Scholar

25 

Taher M: Majid F adibah abdul and Sarmidi MRS: A proanthocyanidin from cinnamomum zeylanicum stimulates phosphorylation of insulin receptor in 3t3-l1 adipocytes. J Teknol. 44:53–68. 2006.

26 

Bouaziz A, Salido S, Linares-Palomino PJ, Sanchez A, Altarejos J, Bartegi A, Salido GM and Rosado JA: Cinnamtannin B-1 from bay wood reduces abnormal intracellular Ca2+ homeostasis and platelet hyperaggregability in type 2 diabetes mellitus patients. Arch Biochem Biophys. 457:235–242. 2007. View Article : Google Scholar

27 

Ben Amor N, Bouaziz A, Romera-Castillo C, Salido S, Linares-Palomino PJ, Bartegi A, Salido GM and Rosado JA: Characterization of the intracellular mechanisms involved in the antiaggregant properties of cinnamtannin B-1 from bay wood in human platelets. J Med Chem. 50:3937–3944. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Bouaziz A, Romera-Castillo C, Salido S, Linares-Palomino PJ, Altarejos J, Bartegi A, Rosado JA and Salido GM: Cinnamtannin B-1 from bay wood exhibits antiapoptotic effects in human platelets. Apoptosis. 12:489–498. 2007. View Article : Google Scholar

29 

Wen L, You L, Yang X, Yang J, Chen F, Jiang Y and Yang B: Identification of phenolics in litchi and evaluation of anticancer cell proliferation activity and intracellular antioxidant activity. Free Radic Biol Med. 84:171–184. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Kashiwada Y, Nonaka G, Nishioka I, Chang JJ and Lee KH: Antitumor agents, 129. Tannins and related compounds as selective cytotoxic agents. J Nat Prod. 55:1033–1043. 1992. View Article : Google Scholar : PubMed/NCBI

31 

Chou TC and Talalay P: Analysis of combined drug effects: A new look at a very old problem. Trends Pharmacol Sci. 4:450–454. 1983. View Article : Google Scholar

32 

Chou TC and Talalay P: Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 22:27–55. 1984. View Article : Google Scholar : PubMed/NCBI

33 

Chou TC: Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 70:440–446. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Kelly C and Cassidy J: Chemotherapy in metastatic colorectal cancer. Surg Oncol. 16:65–70. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Chibaudel B, Tournigand C, André T and de Gramont A: Therapeutic strategy in unresectable metastatic colorectal cancer. Ther Adv Med Oncol. 4:75–89. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Goodwin RA and Asmis TR: Overview of systemic therapy for colorectal cancer. Clin Colon Rectal Surg. 22:251–256. 2009. View Article : Google Scholar :

37 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

38 

Abraha AM and Ketema EB: Apoptotic pathways as a therapeutic target for colorectal cancer treatment. World J Gastrointest Oncol. 8:583–591. 2016. View Article : Google Scholar : PubMed/NCBI

39 

Fridman JS and Lowe SW: Control of apoptosis by p53. Oncogene. 22:9030–9040. 2003. View Article : Google Scholar : PubMed/NCBI

40 

Haupt S, Berger M, Goldberg Z and Haupt Y: Apoptosis - the p53 network. J Cell Sci. 116:4077–4085. 2003. View Article : Google Scholar : PubMed/NCBI

41 

Lane DP: Cancer. p53, guardian of the genome. Nature. 358:15–16. 1992. View Article : Google Scholar : PubMed/NCBI

42 

Higashimoto Y, Saito S, Tong XH, Hong A, Sakaguchi K, Appella E and Anderson CW: Human p53 is phosphorylated on serines 6 and 9 in response to DNA damage-inducing agents. J Biol Chem. 275:23199–23203. 2000. View Article : Google Scholar : PubMed/NCBI

43 

Kaeser MD, Pebernard S and Iggo RD: Regulation of p53 stability and function in HCT116 colon cancer cells. J Biol Chem. 279:7598–7605. 2004. View Article : Google Scholar

44 

Schuler M, Bossy-Wetzel E, Goldstein JC, Fitzgerald P and Green DR: p53 induces apoptosis by caspase activation through mitochondrial cytochrome c release. J Biol Chem. 275:7337–7342. 2000. View Article : Google Scholar : PubMed/NCBI

45 

Soussi T, Ishioka C, Claustres M and Béroud C: Locus-specific mutation databases: Pitfalls and good practice based on the p53 experience. Nat Rev Cancer. 6:83–90. 2006. View Article : Google Scholar : PubMed/NCBI

46 

Siegel R, Ma J, Zou Z and Jemal A: Cancer Stat. 2014:9–29. 2014.

47 

Hemann MT and Lowe SW: The p53-Bcl-2 connection. Cell Death Differ. 13:1256–1259. 2006. View Article : Google Scholar : PubMed/NCBI

48 

Al-Suhaibani ES: Antiproliferation and antiactivity of proanthocyanidins against colorectal cancer cells (Caco-2) line through mitochondrial pathway. Int J Adv Sci Tech Res. 4:152–161. 2015.

49 

Roy AM, Baliga MS, Elmets CA and Katiyar SK: Grape seed proanthocyanidins induce apoptosis through p53, Bax, and caspase 3 pathways. Neoplasia. 7:24–36. 2005. View Article : Google Scholar : PubMed/NCBI

50 

Liu Y and Bodmer WF: Analysis of P53 mutations and their expression in 56 colorectal cancer cell lines. Proc Natl Acad Sci USA. 103:976–981. 2006. View Article : Google Scholar : PubMed/NCBI

51 

Yoo MH, Xu XM, Carlson BA, Patterson AD, Gladyshev VN and Hatfield DL: Targeting thioredoxin reductase 1 reduction in cancer cells inhibits self-sufficient growth and DNA replication. PLoS One. 2:e11122007. View Article : Google Scholar : PubMed/NCBI

52 

Sun G and Kemble DJ: To C or not to C: Direct and indirect redox regulation of Src protein tyrosine kinase. Cell Cycle. 8:2353–2355. 2009. View Article : Google Scholar : PubMed/NCBI

53 

Vaughn AE and Deshmukh M: Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrom c. Nat Cell Biol. 10:1477–1483. 2008. View Article : Google Scholar : PubMed/NCBI

54 

Salvioli S, Storci G, Pinti M, Quaglino D, Moretti L, Merlo-Pich M, Lenaz G, Filosa S, Fico A, Bonafè M, et al: Apoptosis-resistant phenotype in HL-60-derived cells HCW-2 is related to changes in expression of stress-induced proteins that impact on redox status and mitochondrial metabolism. Cell Death Differ. 10:163–174. 2003. View Article : Google Scholar : PubMed/NCBI

55 

Mileo AM and Miccadei S: Polyphenols as modulator of oxidative stress in cancer disease: New therapeutic strategies. Oxid Med Cell Longev. 2016:64756242016. View Article : Google Scholar

56 

Cos P, De Bruyne T, Hermans N, Apers S, Berghe DV and Vlietinck AJ: Proanthocyanidins in health care: Current and new trends. Curr Med Chem. 11:1345–1359. 2004. View Article : Google Scholar : PubMed/NCBI

57 

Lee DH, Lee TH, Jung CH and Kim YH: Wogonin induces apoptosis by activating the AMPK and p53 signaling pathways in human glioblastoma cells. Cell Signal. 24:2216–2225. 2012. View Article : Google Scholar : PubMed/NCBI

58 

Sharif T, Auger C, Alhosin M, Ebel C, Achour M, Etienne-Selloum N, Fuhrmann G, Bronner C and Schini-Kerth VB: Red wine polyphenols cause growth inhibition and apoptosis in acute lymphoblastic leukaemia cells by inducing a redox-sensitive up-regulation of p73 and down-regulation of UHRF1. Eur J Cancer. 46:983–994. 2010. View Article : Google Scholar : PubMed/NCBI

59 

Shankar S and Srivastava RK: Involvement of Bcl-2 family members, phosphatidylinositol 3'-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer. Int J Oncol. 30:905–918. 2007.PubMed/NCBI

60 

Ye R, Goodarzi AA, Kurz EU, Saito S, Higashimoto Y, Lavin MF, Appella E, Anderson CW and Lees-Miller SP: The isoflavonoids genistein and quercetin activate different stress signaling pathways as shown by analysis of site-specific phosphorylation of ATM, p53 and histone H2AX. DNA Repair (Amst). 3:235–244. 2004. View Article : Google Scholar

61 

Su CC, Lin JG, Li TM, Chung JG, Yang JS, Ip SW, Lin WC and Chen GW: Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3. Anticancer Res. 26:4379–4389. 2006.

62 

Méplan C, Richard MJ and Hainaut P: Redox signalling and transition metals in the control of the p53 pathway. Biochem Pharmacol. 59:25–33. 2000. View Article : Google Scholar

63 

Maillet A and Pervaiz S: Redox regulation of p53, redox effectors regulated by p53: A subtle balance. Antioxid Redox Signal. 16:1285–1294. 2012. View Article : Google Scholar

64 

Liu B, Chen Y and St Clair DK: ROS and p53: A versatile partnership. Free Radic Biol Med. 44:1529–1535. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October 2018
Volume 53 Issue 4

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

Sign up for eToc alerts

Recommend to Library

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