ROLE OF ANTI-HISTAMINE IN PROSTATE CANCER
In the prostate gland, cancer cell starts to grow in an uncontrolled
manner, it is mostly found in males and create some fluid that is part
of semen. The cell of the prostate gland appear smaller than normal and
found signs of inflammation in that location which is called
Proliferative inflammatory atrophy. Though it is not cancer it is linked
directly to prostate cancer . The catalytic component of polycomb
repressive complex 2 and a histone lysine methyl transferase, enhancer
of zester homolog 2 (EZH2) has been examined as a chromatin regulator
and for the most part in cancer it is mutated . The Polycomb group
proteins form repressive complexes (PRCs) with varied and preserved
proteins that achieve their purpose as central epigenetic modifiers and
transcriptional regulators in several cellular methods, involving cell
cycle, cell differentiation, DNA injury repair, renewal of stem cell,
and progression as well as the development of disease . Many studies
have reported that EZH2 overexpression boosts cancer cells’
proliferative possessions while striking down EZH2 could encourage
apoptosis and autophagy in cancers. Notably, the new indication
discloses that H3K27 plays a crucial role in epigenetics . Groups of
scientists have reported that EZH2 is a biomarker of destructive
prostate together with breast cancer. The expression range of EZH2 is
deeply immersed in the development of prostate cancer. While in benign
cells EZH2 expression is undetectable, EZH2 mRNA as well as protein
levels are elevated in progressive cancers. In prostate and breast
cancer, EZH2 overexpression indicates an increased opportunity for
metastasis and adverse clinical prognosis . In the quest for novel
therapy plans for progressive cancers, EZH2 grants be a hopeful
treatment target. Remarkable labor has been made to produce little
molecule inhibitors opposite to EZH2. The first identified EZH2
inhibitor 3-deazaneplanocin A (DZNep) targets S-adenosyl-L-homocysteine
hydrolase (SAH), a cofactor known to be essential for EZH2-dependent
methylation . DZNep reduces the EZH2 protein range, but it is not a
perfect EZH2 inhibitor due to its non-specific inhibition of histone
methylation and extreme toxicity in animal models . Therefore, we
testify that a second-generation antagonist of the histamine H1 receptor
ebastine, which has been widely assessed for its toxicity combined with
safety and is approved for anti-allergy therapy in several European
countries, could be reutilized for cancer treatment by aiming EZH2 in
cancer . Many investigators stated that the biomarker EZH2 is
aggressively high in prostate cancer progression. In benign cells, the
EZH2 expression is low and untraceable. The protein levels and mRNA of
EZH2 are high in progressive cancer . It was found that the Increase
possibility of metastases is due to overexpression of EZH2 expression in
prostate cancer. EZH2 stands as a hopeful therapeutic target in the hunt
for new therapeutic strategies for progressive cancer. Newly, many
anti-histamine medications turned out to successfully prevent malignant
tumor progression. In addition to the anti-histamine medication,
astemizole revealed that it can disturb the EZH2-EED relation and
introduce degradation of EZH2. Sadly, astemizole was discontinued since
it can cause ventricular arrhythmia. During the search for further
anti-histamine drugs were examined to observe the possible decrease in
EZH2 protein levels in malignant cells . Ebastine is a new EZH2
inhibitor by targeting specifically the EZH2 transcription and decreases
the EZH2 protein level and trimethylation H3K27 in several cancer cell
lines at below concentration 10 μmol/L. Impairment of progression of
cancer, migration done by ebastine. After the therapy with ebastine
medication, it released the neoplastic things of these malignant cells,
signifying that EZH2 is independent of its enzymatic progression which
is the main target for Ebastine. Furthermore, tumor growth and
progression are successfully reduced by ebastine therapy and improved
the progression-free existence in patients derived drug
resistance-castration prostate cancer in xenograft mice model.
Researchers established that ebastine is a safe and effective
anti-cancer medication for patients with advanced cancer by affecting
the EZH2 oncoprotein .