Paclitaxel and sorafenib: The effective combination of suppressing the self-renewal of cancer stem cells

Hend M. Nawara, Said M. Afify, Ghmkin Hassan, Maram H. Zahra, Marwa N. Atallah, Hager Mansour, Hagar A. Abu Quora, Md Jahangir Alam, Amira Osman, Hiroki Kakuta, Hiroki Hamada, Akimasa Seno, Masaharu Seno

Research output: Contribution to journalArticle

Abstract

“Combination therapy”, which is a treatment modality combining two or more therapeutic agents, is considered a cornerstone of cancer therapy. The combination of anticancer drugs, of which functions are different from the other, enhances the efficiency compared to the monotherapy because it targets cancer cells in a synergistic or an additive manner. In this study, the combination of paclitaxel and sorafenib in low concentration was evaluated to target cancer stem cells, miPS-BT549cmP and miPS-Huh7cmP cells, developed from mouse induced pluripotent stem cells. The synergistic effect of paclitaxel and sorafenib on cancer stem cells was assessed by the inhibition of proliferation, self-renewal, colony formation, and differentiation. While the IC50 values of paclitaxel and sorafenib were approximately ranging between 250 and 300 nM and between 6.5 and 8 µM, respectively, IC50 of paclitaxel reduced to 20 and 25 nM, which was not toxic in a single dose, in the presence of 1 µM sorafenib, which was not toxic to the cells. Then, the synergistic effect was further assessed for the potential of self-renewal of cancer stem cells by sphere formation ability. As a result, 1 µM of sorafenib significantly enhanced the effect of paclitaxel to suppress the number of spheres. Simultaneously, paclitaxel ranging in 1 to 4 nM significantly suppressed not only the colony formation but also the tube formation of the cancer stem cells in the presence of 1 µM sorafenib. These results suggest the combination therapy of paclitaxel and sorafenib in low doses should be an attractive approach to target cancer stem cells with fewer side effects.

Original languageEnglish
Article number1360
JournalCancers
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 2020

Keywords

  • Cancer stem cells
  • Combination therapy
  • Paclitaxel
  • Sorafenib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Nawara, H. M., Afify, S. M., Hassan, G., Zahra, M. H., Atallah, M. N., Mansour, H., Abu Quora, H. A., Alam, M. J., Osman, A., Kakuta, H., Hamada, H., Seno, A., & Seno, M. (2020). Paclitaxel and sorafenib: The effective combination of suppressing the self-renewal of cancer stem cells. Cancers, 12(6), [1360]. https://doi.org/10.3390/cancers12061360