Colorectal cancer (CRC) mortality is mainly caused by patient refractoriness to commonanti-cancer therapies and consequent metastasis formation. Besides, the notorious toxic side effectsof chemotherapy are a concurrent obstacle to be tackled. Thus, new treatment approaches are neededto effectively improve patient outcomes. Compelling evidence demonstrated that cancer stem cells(CSCs) are responsible for treatment failure and relapse. New natural treatment approaches showedcapabilities to selectively target the CSC subpopulation by rendering them targetable by standardcytotoxic compounds. Herein we show the anti-cancer properties of the polymethoxyflavones and prenylflavonoids extracted from Citrus sinensis and Humulus lupulus, respectively. The naturalbiofunctional fractions, singularly and in combination, reduced the cell viability of CRC stem cells (CRCSCs)and synergized with 5-fluorouracil and oxaliplatin (FOX) chemotherapy. These phenomenawere accompanied by a reduced S and G2/M phase of the cell cycle and upregulation of cell deathrelatedgenes. Notably, both phytoextracts in combination with FOX thwarted stemness featuresin CR-CSCs as demonstrated by the impaired clonogenic potential and decreased Wnt pathwayactivation. Extracts lowered the expression of CD44v6 and affected the expansion of metastaticCR-CSCs in patients refractory to chemotherapy. Together, this study highlights the importance ofpolymethoxyflavones and prenylflavonoids as natural remedies to aid oncological therapies.
Original languageEnglish
Pages (from-to)1-16
Number of pages16
Publication statusPublished - 2021

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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