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Multifactorial role of flavonoids in prevention and treatment of various cancers
cytokines such as IL-6, IL-1B and TNF-a. The production a variety of plant foods. Wine drinkers are also considered
of IL-1B was inhibited by inhibition of caspase-1 through at a lower risk of developing cancer than other people.
disruption of NLRP3 inflammasome assembly. mRNA
stability was also reduced due to inhibition of ERK ½ 3.2.1. In vitro studies
activivation (23). The phosphatidylinositol-3 kinase
(PI3K) family of signaling enzymes likely plays a key role Oncology reports published a study, Proanthocyanidins
in inflammation. The PI3k signaling cascade is involved in were investigated for their ability to stimulate programed
leukocyte recruitment and activation and is therefore cell death in human gastric cell line. The findings from this
thought to be involved in inflammation. Apigenin has also study suggest the use of Proanthocyanidins with autophagy
been reported to hinder the PI3k/Akt pathway in cancer inhibitors to significantly increase the rate of apoptosis and
cell lines. The data from a recent study conducted on induce cytotoxicity (29). In agreement with this study,
breast cancer cell lines concluded that flavones such as inhibition of esophageal adenocarcinoma by cranberry
apigenin and luteolin induced apoptosis and cell cycle derived Proanthocyanidins (C-PAC) was investigated. C-
arrest. Hs578T, MDA-MB-231 and MCF-7 breast cancer PAC induced caspase-independent cell death by inducing
cells were used. The underlying mechanism was autophagy in acid-sensitive cell lines. A number of
determined to be the induction of forkhead box O3 signaling pathways were also identified in other cell lines.
(FOXO3a) expression. This subsequently elevated the In-activation of the PI3K/AKT/mTOR pathway,
expression of FOXO3a target genes, including the Cyclin- stimulation of pro-apoptotic proteins, modulation of
dependent kinase inhibitors p21(Cip1) (p21) and p27(kip1) MAPKs and G2-M cell cycle arrest were some of the key
(p27), which increased the levels of activated poly(ADP) factors of action (30). Quercitin is a widely studied
polymerase (PARP) and cytochrome c (24). Kadioglu et al flavonoid attractive for its anti-cancer and anti-
(2015) reported anti-inflammatory effect of the flavonoid proliferative activities. in vitro studies have acertained the
kaempferol against Nf-kB pathway proteins. Nf-kB is an anti-proliferarive outcome of quercetin against human
important factor in the proliferation, inflammation and colon adenocacinoma cells. The underlying mechanism
carcinogenesis. Kaempferol belongs to the flavonol class was associated with a vital upsurge in the expression of the
of flavonoids and its major sources include onions, endocannabinoids receptor (CB1-R) following therapy
cherries, broccoli, kale etc (25). with quercitin. This occurred because CB1-R is an
estrogen responsive receptor and quercetin is similar in
A lot of flavonoids have been studied for their anti- structure to estrogens so it interacts with CB1-R and
inflammatory effects in in vitro studies but there is still regulates cell growth. To further clarify the underlying
lack of evidence with regards to in vivo studies. in vitro mechanism, principal molecular pathways were also
studies focus only on pure doses of flavonoids investigated. Important survival signals like the
administered therefore we cannot be completely sure about PI3K/Akt/mTOR were inhibited, at the same time pro
their effects in humans. This is because humans intake apoptotic JNK/JUN signaling pathways were induced. The
flavonoids indirectly from plant foods and not in pure metabolism of ß-catenin was also modified. The
doses. interactive action of Quercitin with CB1-R was secured by
means of anandamide (Met-F-AEA), a CB1-R agonist,
3.1.2. In vivo studies SR141716, a CB1-R antagonist (31). A number of fruits
have been considered as a valuable source of flavonoids
A number of studies have been conducted in animal and are recommended for the prevention of cancer. Yang S
models. In a recent experiment conducted by Tao et al et al (2015) investigated the anticancer activities of
(2015), Lewis-bearing C57BL/6 mice model was flavonoids extracted from pink lady apples. The flavonoids
established and tumor growth was induced. were divided into two groups; peel-flavonoids and flesh-
Immunomodulatory factors were detected that confirmed flavonoids. It was seen that the both type of flavonoids
the therapeutic effect of flavonoids present in Scutellaria were capable of inhibiting cancer cell growth in a dose
barbata D. Don (SB). It was established that SB could dependent manner (32).
inhibit tumor growth in vivo by regulating the immune
system (26). Many flavonoids are used in combination 3.2.2. In vivo studies
with other molecules and exert a synergistic effect by
enhancing or modulating the activity of the molecule being Many flavonoids have been subjected to studies based
used. Quercitin, a well known flavonoid has been used on animal models. in vivo studies reinforce the efficacy of
along with B-carotene in order to modulate the activity of the drug being used and its underlying mechanism of
B-carotene against NF-kB induced inflammation in action. Toxicity studies can also be conducted on animal
Mongolian gerbils (27). In another study, tricin, a models before any drug is administered to human cohorts.
flavonoid extracted from rice prevented the activation of A number of in vivo studies have been successfully
the NF-kB and the JAK/STAT pathway in vivo. Activation conducted that highlight the anti-cancer activity of
of both STAT1 and STAT3 was inhibited via flavonoids. Bioactive proanthocyanidins decrease the
downregulation of JAK1 and JAK2 (28). accumulation of B-catenin and thereby inhibit growth in
human melanoma cells. Dietary administration of grape
3.2. Anti-cancer effects seed proanthocyanidins (GSPs), suppressed the growth of
nude mice melanoma tumor xenografts.. Furthermore,
Prevention of cancer has been linked with the intake of xenograft growth was reduced in ß-catenin-activated
@Real Academia Nacional de Farmacia. Spain 299
