Targeted
therapy has been a very promising strategy of
drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of
proteins, such as receptors and
hormones.
Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in
chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making
chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of
flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and
estrogenic effects. Several examples of citrus
flavonoids that are potential as chemotherapeutic agents are
tangeretin,
nobiletin,
hesperetin,
hesperidin,
naringenin, and
naringin. Those
flavonoids have been shown to possess inhibition activity on certain
cancer cells' growth through various mechanisms. Moreover, citrus
flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of
cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction. Previous studies showed that
tangeretin suppressed the growth of T47D
breast cancer cells by inhibiting ERK phosphorylation. While in combination with
tamoxifen,
doxorubicin, and
5-FU, respectively, it was proven to be synergist on several
cancer cells.
Hesperidin and
naringenin increased cytotoxicitity of
doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus
flavonoids also performed
estrogenic effect in vivo. One example is
hesperidin having the ability to decrease the concentration of serum and hepatic
lipid and reduce
osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as
natural product to be developed as not only the source of co-chemotherapeutic agents, but also phyto-
estrogens. Therefore, further study needs to be conducted to explore the potential of citrus fruits in overcoming
cancer.