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 .