International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Anticancer effects of D-pinitol in human oral squamous carcinoma cells

  • Shin, Hyun-Chul (Department of Oral Anatomy, School of Dentistry, Pusan National University) ;
  • Bang, Tea-Hyun (Department of Oral Anatomy, School of Dentistry, Pusan National University) ;
  • Kang, Hae-Mi (Department of Oral Anatomy, School of Dentistry, Pusan National University) ;
  • Park, Bong-Soo (Department of Oral Anatomy, School of Dentistry, Pusan National University) ;
  • Kim, In-Ryoung (Department of Oral Anatomy, School of Dentistry, Pusan National University)
  • Received : 2020.10.14
  • Accepted : 2020.12.10
  • Published : 2020.12.31
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Abstract

D-pinitol is an analog of 3-methoxy-D-chiro-inositol found in beans and plants. D-pinitol has anti-inflammatory, antidiabetic, and anticancer effects. Additionally, D-pinitol induces apoptosis and inhibits metastasis in breast and prostate cancers. However, to date, no study has investigated the anticancer effects of D-pinitol in oral cancer. Therefore, in this study, whether the anticancer effects of D-pinitol induce apoptosis, inhibit the epithelial-to-mesenchymal transition (EMT), and arrest cell cycle was investigated in squamous epithelial cells. D-pinitol decreased the survival and cell proliferation rates of CAL-27 and Ca9-22 oral squamous carcinoma cells in a concentration- and time-dependent manner. Evidence of apoptosis, including nuclear condensation, poly (ADP-ribose) polymerase, and caspase-3 fragmentation, was also observed. D-pinitol inhibited the migration and invasion of both cell lines. In terms of EMT-related proteins, E-cadherin was increased, whereas N-cadherin, Snail, and Slug were decreased. D-pinitol also decreased the expression of cyclin D1, a protein involved in the cell cycle, but increased the expression of p21, a cyclin-dependent kinase inhibitor. Hence, D-pinitol induces apoptosis and cell cycle arrest in CAL-27 and Ca9-22 cells, demonstrating an anticancer effect by decreasing the EMT.

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References

  1. Fritz AG. International classification of diseases for oncology: ICD-O. 3rd ed. Geneva: World Health Organization; 2013.
  2. Vokes EE, Weichselbaum RR, Lippman SM, Hong WK. Head and neck cancer. N Engl J Med 1993;328:184-94. doi: 10.1056/NEJM199301213280306.
  3. Laramore GE, Scott CB, al-Sarraf M, Haselow RE, Ervin TJ, Wheeler R, Jacobs JR, Schuller DE, Gahbauer RA, Schwade JG, Campbell BH. Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study 0034. Int J Radiat Oncol Biol Phys 1992;23: 705-13. doi: 10.1016/0360-3016(92)90642-u.
  4. Casiglia J, Woo SB. A comprehensive review of oral cancer. Gen Dent 2001;49:72-82.
  5. Liao S, Xia J, Chen Z, Zhang S, Ahmad A, Miele L, Sarkar FH, Wang Z. Inhibitory effect of curcumin on oral carcinoma CAL-27 cells via suppression of Notch-1 and NF-κB signaling pathways. J Cell Biochem 2011;112:1055-65. doi: 10.1002/jcb.23019.
  6. Lei Y, Zhang D, Yu J, Dong H, Zhang J, Yang S. Targeting autophagy in cancer stem cells as an anticancer therapy. Cancer Lett 2017;393:33-9. doi: 10.1016/j.canlet.2017.02.012.
  7. Nobili S, Lippi D, Witort E, Donnini M, Bausi L, Mini E, Capaccioli S. Natural compounds for cancer treatment and prevention. Pharmacol Res 2009;59:365-78. doi: 10.1016/j.phrs.2009.01.017.
  8. Scotece M, Conde J, Abella V, Lopez V, Pino J, Lago F, Smith AB 3rd, Gómez-Reino JJ, Gualillo O. New drugs from ancient natural foods. Oleocanthal, the natural occurring spicy compound of olive oil: a brief history. Drug Discov Today 2015;20: 406-10. doi: 10.1016/j.drudis.2014.10.017.
  9. Matias I, Buosi AS, Gomes FC. Functions of flavonoids in the central nervous system: astrocytes as targets for natural compounds. Neurochem Int 2016;95:85-91. doi: 10.1016/j.neuint.2016.01.009.
  10. Jagtap S, Meganathan K, Wagh V, Winkler J, Hescheler J, Sachinidis A. Chemoprotective mechanism of the natural compounds, epigallocatechin-3-O-gallate, quercetin and curcumin against cancer and cardiovascular diseases. Curr Med Chem 2009;16:1451-62. doi: 10.2174/092986709787909578.
  11. Rengarajan T, Nandakumar N, Rajendran P, Haribabu L, Nishigaki I, Balasubramanian MP. D-pinitol promotes apoptosis in MCF-7 cells via induction of p53 and Bax and inhibition of Bcl-2 and NF-κB. Asian Pac J Cancer Prev 2014;15:1757-62.doi: 10.7314/apjcp.2014.15.4.1757.
  12. Bates SH, Jones RB, Bailey CJ. Insulin-like effect of pinitol. Br J Pharmacol 2000;130:1944-8. doi: 10.1038/sj.bjp.0703523.
  13. Zhan T, Lou H. Synthesis of azole nucleoside analogues of D-pinitol as potential antitumor agents. Carbohydr Res 2007; 342:865-9. doi: 10.1016/j.carres.2007.01.004.
  14. Rengarajan T, Nandakumar N, Balasubramanian MP. D-Pinitol attenuates 7, 12 dimethylbenz [a] anthracene induced hazards through modulating protein bound carbohydrates, adenosine triphosphatases and lysosomal enzymes during experimental mammary carcinogenesis. J Exp Ther Oncol 2012;10:39-49.
  15. Sethi G, Ahn KS, Sung B, Aggarwal BB. Pinitol targets nuclear factor-kappaB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion, and angiogenesis. Mol Cancer Ther 2008;7:1604-14. doi: 10.1158/1535-7163.MCT-07-2424.
  16. Noguti J, De Moura CF, De Jesus GP, Da Silva VH, Hossaka TA, Oshima CT, Ribeiro DA. Metastasis from oral cancer: an overview. Cancer Genomics Proteomics 2012;9:329-35.
  17. Irani S. Distant metastasis from oral cancer: a review and molecular biologic aspects. J Int Soc Prev Community Dent 2016; 6:265-71. doi: 10.4103/2231-0762.186805.
  18. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009;119:1420-8. doi: 10.1172/JCI39104.
  19. Mk H, Prince S, Mohan AM, Krishnan KV, Devi A. Association of Notch4 with metastasis in human oral squamous cell carcinoma. Life Sci 2016;156:38-46. doi: 10.1016/j.lfs.2016.05.019.
  20. Narayanan CR, Joshi DD, Mujumdar AM, Dhekne VV. Pinitola new anti-diabetic compound from the leaves of Bougainvillea spectabilis. Curr Sci 1987;56:139-41.
  21. White MF. The insulin signalling system and the IRS proteins. Diabetologia 1997;40 Suppl 2:S2-17. doi: 10.1007/s001250051387.
  22. Holman GD, Kasuga M. From receptor to transporter: insulin signalling to glucose transport. Diabetologia 1997;40:991-1003. doi: 10.1007/s001250050780.
  23. Wojciechowska J, Krajewski W, Bolanowski M, Krecicki T, Zatonski T. Diabetes and cancer: a review of current knowledge. Exp Clin Endocrinol Diabetes 2016;124:263-75. doi: 10.1055/s-0042-100910.
  24. Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A. Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PLoS One 2013;8: e71583. doi: 10.1371/journal.pone.0071583.
  25. Garrett CR, Hassabo HM, Bhadkamkar NA, Wen S, Baladandayuthapani V, Kee BK, Eng C, Hassan MM. Survival advantage observed with the use of metformin in patients with type II diabetes and colorectal cancer. Br J Cancer 2012;106:1374-8. doi: 10.1038/bjc.2012.71.
  26. Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH, Huang YC. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals. BMC Cancer 2011;11:20. doi: 10.1186/1471-2407-11-20.
  27. Lin TH, Tan TW, Tsai TH, Chen CC, Hsieh TF, Lee SS, Liu HH, Chen WC, Tang CH. D-pinitol inhibits prostate cancer metastasis through inhibition of αVβ3 integrin by modulating FAK, c-Src and NF-κB pathways. Int J Mol Sci 2013;14:9790-802. doi: 10.3390/ijms14059790.
  28. Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature 2001;411:342-8. doi: 10.1038/35077213.
  29. Kastan MB, Bartek J. Cell-cycle checkpoints and cancer. Nature 2004;432:316-23. doi: 10.1038/nature03097.
  30. Rengarajan T, Nandakumar N, Rajendran P, Ganesh MK, Balasubramanian MP, Nishigaki I. D-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB. J Physiol Biochem 2015;71:191-204. doi: 10.1007/s13105-015-0397-9.
  31. Angadi PV, Patil PV, Angadi V, Mane D, Shekar S, Hallikeri-math S, Kale AD, Kardesai SG. Immunoexpression of epithelial mesenchymal transition proteins E-cadherin, β-catenin, and N-cadherin in oral squamous cell carcinoma. Int J Surg Pathol 2016;24:696-703. doi: 10.1177/1066896916654763.
  32. Micalizzi DS, Farabaugh SM, Ford HL. Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia 2010;15:117-34. doi: 10.1007/s10911-010-9178-9.