TY - JOUR
T1 - Nobiletin and xanthohumol sensitize colorectal cancer stem cells to standard chemotherapy
AU - Turdo, Alice
AU - Glaviano, Antonino
AU - Pepe, Giacomo
AU - Calapà, Federica
AU - Raimondo, Stefania
AU - Fiori, Micol Eleonora
AU - Carbone, Daniela
AU - Basilicata, Manuela Giovanna
AU - Di Sarno, Veronica
AU - Ostacolo, Carmine
AU - Parrino, Barbara
AU - Cascioferro, Stella
AU - Pecoraro, Camilla
AU - Di Franco, Simone
AU - Bellavia, Diana
AU - Gaggianesi, Miriam
AU - Veschi, Veronica
AU - Iacono, Melania Lo
AU - Ganduscio, Gloria
AU - Pantina, Vincenzo Davide
AU - Mangiapane, Laura Rosa
AU - Bongiorno, Maria Rita
AU - Alessandro, Riccardo
AU - Todaro, Matilde
AU - De Maria Marchiano, Ruggero
AU - Diana, Patrizia
AU - Campiglia, Pietro
AU - Stassi, Giorgio
PY - 2021
Y1 - 2021
N2 - Colorectal cancer (CRC) mortality is mainly caused by patient refractoriness to common anti-cancer therapies and consequent metastasis formation. Besides, the notorious toxic side effects of chemotherapy are a concurrent obstacle to be tackled. Thus, new treatment approaches are needed to effectively improve patient outcomes. Compelling evidence demonstrated that cancer stem cells (CSCs) are responsible for treatment failure and relapse. New natural treatment approaches showed capabilities to selectively target the CSC subpopulation by rendering them targetable by standard cytotoxic compounds. Herein we show the anti-cancer properties of the polymethoxyflavones and prenylflavonoids extracted from Citrus sinensis and Humulus lupulus, respectively. The natural biofunctional fractions, singularly and in combination, reduced the cell viability of CRC stem cells (CR-CSCs) and synergized with 5-fluorouracil and oxaliplatin (FOX) chemotherapy. These phenomena were accompanied by a reduced S and G2/M phase of the cell cycle and upregulation of cell death-related genes. Notably, both phytoextracts in combination with FOX thwarted stemness features in CR-CSCs as demonstrated by the impaired clonogenic potential and decreased Wnt pathway activation. Extracts lowered the expression of CD44v6 and affected the expansion of metastatic CR-CSCs in patients refractory to chemotherapy. Together, this study highlights the importance of polymethoxyflavones and prenylflavonoids as natural remedies to aid oncological therapies.
AB - Colorectal cancer (CRC) mortality is mainly caused by patient refractoriness to common anti-cancer therapies and consequent metastasis formation. Besides, the notorious toxic side effects of chemotherapy are a concurrent obstacle to be tackled. Thus, new treatment approaches are needed to effectively improve patient outcomes. Compelling evidence demonstrated that cancer stem cells (CSCs) are responsible for treatment failure and relapse. New natural treatment approaches showed capabilities to selectively target the CSC subpopulation by rendering them targetable by standard cytotoxic compounds. Herein we show the anti-cancer properties of the polymethoxyflavones and prenylflavonoids extracted from Citrus sinensis and Humulus lupulus, respectively. The natural biofunctional fractions, singularly and in combination, reduced the cell viability of CRC stem cells (CR-CSCs) and synergized with 5-fluorouracil and oxaliplatin (FOX) chemotherapy. These phenomena were accompanied by a reduced S and G2/M phase of the cell cycle and upregulation of cell death-related genes. Notably, both phytoextracts in combination with FOX thwarted stemness features in CR-CSCs as demonstrated by the impaired clonogenic potential and decreased Wnt pathway activation. Extracts lowered the expression of CD44v6 and affected the expansion of metastatic CR-CSCs in patients refractory to chemotherapy. Together, this study highlights the importance of polymethoxyflavones and prenylflavonoids as natural remedies to aid oncological therapies.
KW - Anti-cancer therapy
KW - Cancer stem cells
KW - Colorectal cancer
KW - Flavonoids
KW - Natural biofunctional molecules
KW - Nobiletin
KW - Xanthohumol
KW - Anti-cancer therapy
KW - Cancer stem cells
KW - Colorectal cancer
KW - Flavonoids
KW - Natural biofunctional molecules
KW - Nobiletin
KW - Xanthohumol
UR - http://hdl.handle.net/10807/183051
U2 - 10.3390/cancers13163927
DO - 10.3390/cancers13163927
M3 - Article
SN - 2072-6694
VL - 13
SP - 3927-N/A
JO - Cancers
JF - Cancers
ER -
