CR-CSphCs are resistant to chemotherapy. (a) Cell proliferation percentage of CR-CSphCs (#3, #8, and #59) and CRC cell lines (HCT116 and RKO) treated with 0.1 µM, 0.5 µM, 1 µM, 2.5 µM, 5 µM, and 10 µM of FOX chemotherapy for 48 h. Data are represented as mean ± SD of three independent experiments. IC50 values are indicated in the right panel; (b) chromatographic profiles of polymethoxyflavones and chemical structure of Nobiletin, isolated from Citrus sinensis; (c) chromatographic profiles of prenylflavonoids and chemical structure of Xanthohumol, isolated from Humulus lupulus; (d) qualitative profile of isolated polyphenolic fractions; (e) NCF, XCF, and Mix (50% NCF plus 50% XCF) were firstly extracted through lyophilization and then solubilized in methanol. CR-CSphCs and CRC cell lines were exposed to extracts, either singularly or in combination with FOX chemotherapy.