ANTI-CSC COMBINATION THERAPY USING WNT SIGNALING-TARGETED DRUG

  • Muthu Dhandapani PG & Research Department of Zoology and Biotechnology, A.V.V.M. Sri Pushpam College (Autonomous), Poondi, Thanjavur-613 503, Tamil Nadu.
  • Babu Balakrishnan PG & Research Department of Zoology and Biotechnology, A.V.V.M. Sri Pushpam College (Autonomous), Poondi, Thanjavur-613 503, Tamil Nadu.
  • Ganesan Sivamani PG & Research Department of Zoology and Biotechnology, A.V.V.M. Sri Pushpam College (Autonomous), Poondi, Thanjavur-613 503, Tamil Nadu.

Abstract

Dysfunctions of Wnt, Hedgehog and Notch pathways are evident in multiple tumor types and malignancies. A number of studies have suggested that dysregulation of Wnt/β-catenin signaling occurs in human breast cancer. Specifically, inhibition of Wnt/ β-catenin pathway is implicated in arresting of cancer stem cells (CSCs), a small subset of cancer cells capable of self-renewal and differentiation into heterogeneous tumor cells. Here, we investigated tumor initiating property of breast cancer stem cell in-vitro with XAV-939 an inhibitor of Wnt/β-catenin signaling pathway. Targeting Wnt/β-catenin signaling with this inhibitor represents a promising strategy to suppress metastasis.


Keywords: Cancer Stem Cell, 3D Mammosphere, Wnt/β-catenin, metastasis, CD44+/CD24

Downloads

Download data is not yet available.

Author Biographies

Muthu Dhandapani, PG & Research Department of Zoology and Biotechnology, A.V.V.M. Sri Pushpam College (Autonomous), Poondi, Thanjavur-613 503, Tamil Nadu.

PG & Research Department of Zoology and Biotechnology, A.V.V.M. Sri Pushpam College (Autonomous), Poondi, Thanjavur-613 503, Tamil Nadu.

Babu Balakrishnan, PG & Research Department of Zoology and Biotechnology, A.V.V.M. Sri Pushpam College (Autonomous), Poondi, Thanjavur-613 503, Tamil Nadu.

PG & Research Department of Zoology and Biotechnology, A.V.V.M. Sri Pushpam College (Autonomous), Poondi, Thanjavur-613 503, Tamil Nadu.

Ganesan Sivamani, PG & Research Department of Zoology and Biotechnology, A.V.V.M. Sri Pushpam College (Autonomous), Poondi, Thanjavur-613 503, Tamil Nadu.

PG & Research Department of Zoology and Biotechnology, A.V.V.M. Sri Pushpam College (Autonomous), Poondi, Thanjavur-613 503, Tamil Nadu.

References

1. Ferlay J., Soerjomataram I, Dikshit R et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 2015; 136(5):E359–E386.
2. DeSantis CE., Bray F., Ferlay J., et al. International variation in female breast cancer incidence and mortality rates. Cancer Epidemiol Biomarkers Prev, 2015; 24(10):1495–1506.
3. Hashim D., Boffetta P., La Vecchia C., et al. The global decrease in cancer mortality: trends and disparities. Ann Oncol, 2016; 27(5):926–933.
4. Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. Lancet, 2012; 380(9855): 1778–1786.
5. Pace LE., Keating NL. A systematic assessment of benefits and risks to guide breast cancer screening decisions. JAMA, 2014; 311(13):1327–1335.
6. Moja L., Tagliabue L., Balduzzi S., et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev, 2012; 4:CD006243.
7. Koury J., Zhong L., Hao J. Targeting Signaling Pathways in Cancer Stem Cells for Cancer Treatment. Stem Cells International, 2017; 2017:2925869. doi:10.1155/2017/2925869.
8. Hermann P.C., et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell, 2007; 1:313–23.
9. Mani S.A., et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 2008; 133:704–15.
10. Howard B., Ashworth A. Signaling pathways implicated in early mammary gland morphogenesis and breast cancer. PLoS Genet, 2006; 2:e112.
11. Basu S., Haase G., Ben-Ze'ev A. Wnt signaling in cancer stem cells and colon cancer metastasis. F1000 Research, 2016; 5(699).
12. Mukherjee S., Mazumdar M., Chakraborty S., et al. Curcumin inhibits breast cancer stem cell migration by amplifying the E-cadherin/β-catenin negative feedback loop. Stem Cell Research and Therapy, 2014; 5 (5):116.
13. Reya T., Duncan A. W., Ailles L., et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature, 2003; 423(6938):409–414.
14. Zhang X., Lou Y., Wang H., et al. Wnt signaling regulates the stemness of lung cancer stem cells and its inhibitors exert anticancer effect on lung cancer SPC-A1 cells. Medical Oncology. 2015; 32(4): 95.
15. Vasanthakumar S., Sasikala P., Padma M., et al. EpCAM as a novel therapeutic target for hepatocellular carcinoma. Journal of Oncological Sciences, 2007; 3:71-76.
16. Malanchi I., Peinado H., Kassen D., et al. Cutaneous cancer stem cell maintenance is dependent on β-catenin signalling. Nature, 2008; 452(7187):650–653.
17. Jang GB., Kim JY., Cho SD., Park KS., Jung JY., Lee HY., et al. Blockade of Wnt/beta-catenin signaling suppresses breast cancer metastasis by inhibiting CSC-like phenotype. Sci Rep, 2015; 5:12465.
18. Al-Hajj M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J. & Clarke, M.F. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci, 2003; USA100:3983–8.
19. Liu, H et al. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Proc Natl Acad Sci, 2010; USA107:18115–20.
20. Zardawi S.J., O’Toole S.A., Sutherland R.L. & Musgrove, E.A. Dysregulation of Hedgehog, Wnt and Notch signalling pathways in breast cancer. Histol Histopathol, 2009; 24:385–98.
21. Lopez-Knowles E.et al. Cytoplasmic localization of beta-catenin is a marker of poor outcome in breast cancer patients. Cancer Epidemiol Biomarkers Prev, 2010; 19:301–9.
22. Xiao-Hong T., Wei-Jian H. Yan F., et al. XAV939, a tankyrase 1 inhibitior, promotes cell apoptosis in neuroblastoma cell lines by inhibiting Wnt/β-catenin signaling pathway. J Exp & Clin Cancer Res, 2013; 32:100.
Statistics
50 Views | 30 Downloads
How to Cite
Dhandapani, M., Balakrishnan, B., & Sivamani, G. (2018). ANTI-CSC COMBINATION THERAPY USING WNT SIGNALING-TARGETED DRUG. Journal of Drug Delivery and Therapeutics, 8(5-s), 139-142. https://doi.org/10.22270/jddt.v8i5-s.1921
Section
Research