DOI QR코드

DOI QR Code

Cell Cycle Modulation of MCF-7 and MDA-MB-231 by a Sub-Fraction of Strobilanthes crispus and its Combination with Tamoxifen

  • Yaacob, Nik Soriani (Department of Chemical Pathology, Universiti Sains Malaysia Health Campus) ;
  • Kamal, Nik Nursyazni Nik Mohamed (Department of Chemical Pathology, Universiti Sains Malaysia Health Campus) ;
  • Wong, Kah Keng (Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia Health Campus) ;
  • Norazmi, Mohd Nor (School of Health Sciences, Universiti Sains Malaysia Health Campus)
  • Published : 2016.01.11

Abstract

Background: Cell cycle regulatory proteins are suitable targets for cancer therapeutic development since genetic alterations in many cancers also affect the functions of these molecules. Strobilanthes crispus (S. crispus) is traditionally known for its potential benefits in treating various ailments. We recently reported that an active sub-fraction of S. crispus leaves (SCS) caused caspase-dependent apoptosis of human breast cancer MCF-7 and MDA-MB-231 cells. Materials and Methods: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle-related transcripts was analysed based on a previous microarray dataset. Results: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of $ER{\alpha}$ protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied. Conclusions: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents.

Keywords

Strobilanthes crispus;tamoxifen;cell cycle;estrogen receptor;MCF-7;MDA-MB-231

Acknowledgement

Supported by : USM, Malaysian Ministry of Science, Technology and Innovation

References

  1. Majumder B, Wahle KWJ, Moir S, et al (2002). Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells. FASEB J, 16, 1447-9. https://doi.org/10.1096/fj.01-0720fje
  2. Park C, Kim GY, Kim GD, et al (2006). Induction of G2/M arrest and inhibition of cyclooxygenase-2 activity by curcumin in human bladder cancer T24 cells. Oncol Rep, 15, 1225-31.
  3. Paruthiyil S, Parmar H, Kerekatte V, et al (2004). Estrogen receptor $\beta$ inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest. Cancer Res, 64, 423-8. https://doi.org/10.1158/0008-5472.CAN-03-2446
  4. Pflaum J, Schlosser S, Muller M (2014). p53 family and cellular stress responses in cancer. Front Oncol, 4, 285.
  5. Steigerova J, Oklest'kova J, Levkova M, et al (2010). Brassinosteroids cause cell cycle arrest and apoptosis of human breast cancer cells. Chem Biol Interact, 188, 487-96. https://doi.org/10.1016/j.cbi.2010.09.006
  6. Richardson AL, Wang ZC, De Nicolo A, et al (2006). X chromosomal abnormalities in basal-like human breast cancer; Cancer Cell, 9, 121-32. https://doi.org/10.1016/j.ccr.2006.01.013
  7. Stewart ZA, Westfall MD, Pietenpol JA (2003). Cell-cycle dysregulation and anticancer therapy. Trends Pharmacol Sci, 24, 139-45. https://doi.org/10.1016/S0165-6147(03)00026-9
  8. Wang X, Di Pasqua AJ, Govind S, et al (2011). Selective depletion of mutant p53 by cancer chemopreventive isothiocyanates and their structure-activity relationships. J Med Chem, 54, 809-16. https://doi.org/10.1021/jm101199t
  9. Yaacob NS, Hamzah N, Nik Mohamed Kamal NN, et al (2010). Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro. BMC Complement Altern Med, 10, 42. https://doi.org/10.1186/1472-6882-10-42
  10. Yaacob NS, Nik Mohamed Kamal NN, Norazmi MN (2014). Synergistic anticancer effects of a bioactive subfraction of Strobilanthes crispus and tamoxifen on MCF-7 and MDAMB- 231 human breast cancer cell lines. BMC Complement Altern Med, 14, 252. https://doi.org/10.1186/1472-6882-14-252
  11. Yu J, Guo QL, You QD, et al (2006). Gambogic acid-induced G2/M phase cell-cycle arrest via disturbing CDK7-mediated phosphorylation of CDC2/p34 in human gastric carcinoma BGC-823 cells. Carcinogenesis, 28, 632-8. https://doi.org/10.1093/carcin/bgl168
  12. de Jong JS, van Diest PJ, Michalides RJAM, Baak JPA (1999). Concerted overexpression of the genes encoding p21 and cyclin D1 is associated with growth inhibition and differentiation in various carcinomas. Mol Pathol, 52, 78-83. https://doi.org/10.1136/mp.52.2.78
  13. Doisneau-Sixou SF, Sergio CM, Carroll JS, et al (2003). Estrogen and antiestrogen regulation of cell cycle progression in breast cancer cells. Endocr-Relat Cancer, 10, 179-86. https://doi.org/10.1677/erc.0.0100179
  14. Freund A, Chauveau C, Brouillet J-P, et al (2003). IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells. Oncogene, 22, 256-65. https://doi.org/10.1038/sj.onc.1206113
  15. Fu M, Wang C, Li Z, Sakamaki T, Pestell RG (2004). Cyclin D1, normal and abnormal functions. Endocrinol, 145, 5439-47. https://doi.org/10.1210/en.2004-0959
  16. Garrett MD (2001). Cell cycle control and cancer. Curr Sci, 81, 515-22.
  17. Helguero LA, Faulds MH, Gustadsson JA, Haldosen LA (2005). Estrogen receptor alpha (ER$\alpha$) and beta (ER$\beta$) differentially regulate proliferation and apoptosis of the normal murine mammary epithelial cell line HC11. Oncogene, 24, 6605-16. https://doi.org/10.1038/sj.onc.1208807
  18. Hui R, Finney GL, Carroll JS, et al (2002). Constitutive overexpression of cyclin D1 but not cyclin E confers acute resistance to antiestrogen in T-47D breast cancer cells. Cancer Res, 62, 6916-23.
  19. Ichikawa A, Ando J, Suda K (2008). G1 arrest and expression of cyclin-dependent kinase inhibitors in tamoxifen-treated MCF-7 human breast cancer cells. Human Cell, 21, 28-37. https://doi.org/10.1111/j.1749-0774.2008.00048.x
  20. Jedinak A, Sliva D (2008). Pleurotus ostreatus inhibits proliferation of human breast and colon cancer cells through p53-dependent as well as p53-independent pathway. Int J Oncol, 33, 1307-13.
  21. Katzenellenbogen BS, Montano MM, Ediger TR, et al (2000). Estrogen receptors, selective ligands, partners, and distinctive pharmacology. Recent Prog Horm Res, 55, 163-93.
  22. Kurebayashi J, Otsuki T, Kunisue H, et al (2000). Expression levels of estrogen receptor-$\alpha$, estrogen receptor-$\beta$, coactivators, and corepressors in breast cancer. Clin Cancer Res, 6, 512-8.
  23. Lange CA, Yee D (2011). Killing the second messenger, targeting loss of cell cycle control in endocrine-resistant breast cancer. Endocr-Relat Cancer, 18, 19-24. https://doi.org/10.1530/ERC-11-0112
  24. Lindberg MK, Moverare S, Skrtic S, et al (2003). Estrogen receptor (ER)-$\beta$ reduces ER$\alpha$-regulated gene transcription, supporting a "ying yang" relationship between ER$\alpha$ and ER$\beta$ in mice. Mol Endocrinol, 17, 203-8. https://doi.org/10.1210/me.2002-0206
  25. Alao JP (2004). The regulation of cyclin D1 degradation, roles in cancer development and the potential for therapeutic invention. Mol Cancer, 6, 24.
  26. Alenzi FQB (2004). Links between apoptosis, proliferation and the cell cycle. Br J Biomed Sci, 61, 99-102. https://doi.org/10.1080/09674845.2004.11732652
  27. Butt AJ, McNeil CM, Musgrove EA, Sutherland RL (2005). Downstream targets of growth factor and oestrogen signalling and endocrine resistance, the potential roles of c-Myc, cyclin D1 and cyclin E. Endocr-Relat Cancer, 12, 547-59.
  28. Choi JA, Kim JY, Lee JY, et al (2001). Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. Int J Oncol, 19, 837-44.
  29. Chong HZ, Rahmat A, Yeap SK, et al (2012). In vitro cytotoxicity of Strobilanthes crispus ethanol extract on hormone dependent human breast adenocarcinoma MCF-7 cells. BMC Complement Altern Med, 12, 35. https://doi.org/10.1186/1472-6882-12-35

Cited by

  1. Towards the mode of action of Strobilanthes crispus through integrated computational and experimental analyses vol.26, pp.4, 2017, https://doi.org/10.1007/s13562-017-0407-9