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Page 10 of 36 Dave et al. J Cancer Metastasis Treat 2020;6:46 I http://dx.doi.org/10.20517/2394-4722.2020.106
Figure 4. Sulforaphane and KEAP-nrf2 signaling. Sulforaphane enters cells and interacts with Kelch-like ECH associated protein. This
prevents nrf2 degradation and leads to downstream anti-inflammatory and antioxidant effects. NF-κB: nuclear factor-κB
reduced HDAC activity, and increased acetylated histones 3 and 4 [131] . HDAC inhibitory effects of
sulforaphane were also demonstrated with a mouse model bearing a colon cancer xenograft [132] . The United
States Food and Drug Administration approved the use of HDAC inhibitors for the treatment of cancer, so
investigation of phytochemicals such as sulforaphane is reasonable [133] . In a phase II clinical trial involving
patients with recurrent prostate cancer, administration of 200 μmol/day of sulforaphane rich extracts for
20 weeks did not produce a reduction in prostate specific antigen (PSA) levels by at least 50%. However,
PSA doubling time was increased [134] . In a double-blinded study, there was a significant reduction in PSA
levels in prostate cancer patients post-prostatectomy when given 60 mg sulforaphane orally with cancer
therapy, followed by 2 months of sulforaphane with no other treatment [135] . The promising results observed
with sulforaphane in these clinical trials suggest the use of an HDAC inhibitor in combination with a
chemopreventive agent for the treatment of prostate cancer.
ANTHOCYANINS
Chemical properties of anthocyanins
Anthocyanins are water-soluble secondary polyphenolic metabolites produced by plants [136] . The substances
are classified under the flavonoid group and provide blue, red, and purple pigmentation for plants. The basic
chemical structure of an anthocyanin contains anthocyanidin without a sugar moiety. The anthocyanidins
are comprised of an aromatic ring (A) which is bonded to a heterocyclic ring (C) that includes oxygen, and
this is similarly attached to carbon-carbon bonds linking to a third aromatic ring (B) [137] . There is a vast
number of anthocyanins present in nature, the most common being petunidin, pelargonidin, delphinidin,
peonidin, malvidin, and cyanidin. The only difference between these compounds is the nature and the