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Combination treatment with flavonoid morin and telomerase inhibitor MST‑312 reduces cancer stem cell traits by targeting STAT3 and telomerase

  • Authors:
    • Seyung S. Chung
    • Bryant Oliva
    • Sami Dwabe
    • Jaydutt V. Vadgama
  • View Affiliations / Copyright

    Affiliations: Division of Cancer Research and Training, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA
    Copyright: © Chung et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 487-498
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    Published online on: May 31, 2016
       https://doi.org/10.3892/ijo.2016.3546
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Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. The malignant CRC that undergoes metastasis in the advanced stage is usually refractory to existing chemotherapy and shows a poor prognosis. However, to date, efficient targeted-therapy for metastatic CRC is ill-defined. We tested the hypothesis that combined treatment of flavonoid morin and telomerase inhibitor MST‑312 may reduce the cancer stem cell (CSC) traits. To characterize CSC phenotype, we performed the CD133/CD44 subpopulation profiling, tumorsphere formation assay, cell invasion assay and wound healing assay. We have examined the augmenting effects of the combined treatment of morin and MST‑312 for 5-FU (5-fluorouracil) efficacy in human colorectal cancer. Morin and MST‑312 combined treatment reduced CD133 (+) and CD44 (+) subpopulations in human colorectal and breast cancer cells, respectively. Tumorsphere formation and cell invasiveness were decreased with the morin and MST‑312 combination treatment. Consistent with these data, morin and MST‑312 treatment decreased the wound healing capacity of human breast cancer cells. Stress and apoptosis antibody arrays revealed that there were specific upregulated and downregulated proteins resulting from different treatments. Phosphorylation levels of BAD, p53 and Chk1 were enhanced upon morin/MST‑312 treatments in HT-29 cells, whereas caspase-3 cleavage level and expression of IκBα were downregulated by combined morin/MST‑312 treatment in SW620 cells. Finally, morin and MST‑312 co-treatment further augmented the 5-FU efficacy, chemosensitizing the 5-FU resistant human colorectal cancer cells. Taken together, our study suggests that novel targeted-therapy can be implemented by using flavonoid morin and telomerase inhibitor MST‑312 for improved cancer prognosis.
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Copy and paste a formatted citation
Spandidos Publications style
Chung SS, Oliva B, Dwabe S and Vadgama JV: Combination treatment with flavonoid morin and telomerase inhibitor MST‑312 reduces cancer stem cell traits by targeting STAT3 and telomerase. Int J Oncol 49: 487-498, 2016.
APA
Chung, S.S., Oliva, B., Dwabe, S., & Vadgama, J.V. (2016). Combination treatment with flavonoid morin and telomerase inhibitor MST‑312 reduces cancer stem cell traits by targeting STAT3 and telomerase. International Journal of Oncology, 49, 487-498. https://doi.org/10.3892/ijo.2016.3546
MLA
Chung, S. S., Oliva, B., Dwabe, S., Vadgama, J. V."Combination treatment with flavonoid morin and telomerase inhibitor MST‑312 reduces cancer stem cell traits by targeting STAT3 and telomerase". International Journal of Oncology 49.2 (2016): 487-498.
Chicago
Chung, S. S., Oliva, B., Dwabe, S., Vadgama, J. V."Combination treatment with flavonoid morin and telomerase inhibitor MST‑312 reduces cancer stem cell traits by targeting STAT3 and telomerase". International Journal of Oncology 49, no. 2 (2016): 487-498. https://doi.org/10.3892/ijo.2016.3546
Copy and paste a formatted citation
x
Spandidos Publications style
Chung SS, Oliva B, Dwabe S and Vadgama JV: Combination treatment with flavonoid morin and telomerase inhibitor MST‑312 reduces cancer stem cell traits by targeting STAT3 and telomerase. Int J Oncol 49: 487-498, 2016.
APA
Chung, S.S., Oliva, B., Dwabe, S., & Vadgama, J.V. (2016). Combination treatment with flavonoid morin and telomerase inhibitor MST‑312 reduces cancer stem cell traits by targeting STAT3 and telomerase. International Journal of Oncology, 49, 487-498. https://doi.org/10.3892/ijo.2016.3546
MLA
Chung, S. S., Oliva, B., Dwabe, S., Vadgama, J. V."Combination treatment with flavonoid morin and telomerase inhibitor MST‑312 reduces cancer stem cell traits by targeting STAT3 and telomerase". International Journal of Oncology 49.2 (2016): 487-498.
Chicago
Chung, S. S., Oliva, B., Dwabe, S., Vadgama, J. V."Combination treatment with flavonoid morin and telomerase inhibitor MST‑312 reduces cancer stem cell traits by targeting STAT3 and telomerase". International Journal of Oncology 49, no. 2 (2016): 487-498. https://doi.org/10.3892/ijo.2016.3546
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