A standardized extract of red orange juice obtained from three pigmented varieties of
C. sinensis (Moro, Tarocco, Sanguinello) inhibited proliferation of normal human prostatic epithelial cell line PZ-HPV-7 at 10
−3 g/mL and lung fibroblast cell line of Chinese hamsters V79-4 at 10
−4 g/mL. Untreated controls just with 5 × 104 cells/well were employed [
63]. The juice of fruits of
C. sinensis (L) Osb. (cv. Washington Navel and cv. Sanguinello) at concentrations of 82.6% and 73% showed 100% antiproliferative activity against the cell lines: K562 (human chronic myelogenous leukemia) and HL-60 (human leukemia). In the same way concentration of 10% showed 90.5% antiproliferative activity against MCF-7 cells (human breast adenocarcinoma) [
64]. Another study showed the anti-proliferative and cytostatic effects of
C.
sinensis juice on the growth of guinea corn radicle has been documented. In this study it was shown that percentage of inhibition at concentrations of 5%, 10%, 20%, 40% and 60% (
v/
v) were of 18.94%, 72.37%, 91.96%, 99.72%, and 100% respectively. The concentrations of 40% and 60% (
v/
v) of juice showed cytostatic effects compared with the standard drug methotrexate (50 µg/mL) which showed 77.71% of inhibition [
65]. Polymethoxyflavones isolated from peels of
C. sinesis showed activity on human lung cancer cells. Nobiletin and 3,5,6,7,8,3′,4′-heptamethoxyflavone had a half inhibitory concentration (IC
50) of 50 µM against H1299 cells, while 5-hydroxy-3,7,8,3′,4′-pentamethoxyflavone and 5-hydroxy-3,6,7,8,3′,4′-hexamethoxy-flavone showed IC
50 values of 16.5 µM against H1299 cells. The above four flavonoids had similar activity towards human lung cancer cells H441 and H460 [
66]. Cold-pressed orange peel oil containing a mixture of non-hydroxylated polymethoxyflavones (75.1%) and hydroxylated polymethoxyflavones (5.44%) and a mixture containing only hydroxylated polymethoxyflavones (97.2%) induce apoptosis in breast cancer cells MCF-7 with a Minimal Effective Concentration (ECmin) of 9.25 and 4.62 µg/mL, respectively [
67]. Other study with Apc(Min/+) mice (a mouse model for human familial adenomatous polyposis) fed with 5% of orange peel extract containing 30% polymethoxyflavones (tangeretin 19.0%, heptamethoxyflavone 15.24%, tetramethoxyflavone 13.6%, nobiletin 12.49%, hexamethoxyflavone 11.06 and sinensitin 9.16%) decreased the development of tumors [
68]. Several compounds also obtained from peel extract presented inhibitory activities against the proliferation of cells (IC
50) and induced apoptosis (AC
50) of HL-60 cell lines: 3,5,6,7,8,3′,4′-heptamethoxyflavone (IC
50 13.31 ± 1.28 µM; AC
50 33.88 ± 0.01 µM), nobiletin (IC
50 41.50 ± 7.01 µM; AC
50 > 100 µM), 3,5,6,7,3′,4′-hexamethoxyflavone (IC
50 20.59 ± 1.01 µM; AC
50 92.10 ± 5.67 µM), 3′-hydroxy-5,6,7,8,4′-pentamethoxyflavone (IC
50 52.72 ± 0.22 µM; AC
50 94.62 ± 1.50 µM), 4′-hydroxy-5,6,7,8,3′-pentamethoxyflavone (IC
50 47.41 ± 3.64 µM; AC
50 87.10 ± 7.83 µM), 5-hydroxy-3,6,7,8,3′,4′-hexa-methoxyflavone (IC
50 4.16 ± 2.33 µM; AC
50 5.90 ± 0.11 µM), 5-hydroxy-3,6,7,3′,4′-pentamethoxyflavone (IC
50 2.07 ± 2.56 µM; AC
50 5.87 ± 0.13 µM) [
69]. Another study demonstrated that D-limonene rich volatile oil obtained from blood oranges inhibited proliferation of colorectal cancer cells HT-29 at 1000 ppm [
70]. Flavones and isoflavones showed inhibition of cell proliferation and induction of cell apoptosis on MCF-7 breast cancer cells: 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone (IC
50 2.50 μM; (ECmin) 1.56 μM), 5,6,7,4′-tetramethoxyflavone (IC
50 10.5 μM; ECmin 3.15 μM ), 3,5,6,7,8,3′,4′-heptamethoxyflavone (IC
50 > 50 μM; ECmin 50 μM), 5,6,7,3′,4′-pentamethoxyflavone (IC
50 > 50 μM; ECmin >50 μM). A Cell numbers (1 × 10
3 cells) were presented as control [
71]. The aqueous extract of
C. sinensis L. (Osbeck) showed significant cytotoxic effect on cells of the Yoshida ascites sarcoma [
72]. 4′-Geranyloxyferulic (0.141 ± 0.011 mg/g) obtained C.
sinensis depicted a potential chemopreventive effect [
73]. All of these antiproliferative features suggest that properties of extracts and pure compounds particularly flavonoids contained in
C. sinensis, could be explored for chemopreventive and therapeutic purposes in cancer.