Dual-specificity phosphatase 6 (DUSP6): a review of its molecular characteristics and clinical relevance in cancer

Nutritional or dietary factors have drawn attention due to their potential as an effective chemopreventive agent, which is considered a more rational strategy in cancer treatment. This study was designed to evaluate the effect of IP₆extracted from rice bran on azoxymethane- (AOM-) induced colorectal cancer (CRC) in rats. Initially, male Sprague Dawley rats were divided into 5 groups, with 6 rats in each group. The rats received two intraperitoneal (i.p.) injections of AOM in saline (15 mg/kg body weight) over a 2-week period to induce CRC. IP₆was given in three concentrations, 0.2% (w/v), 0.5% (w/v), and 1.0% (w/v), via drinking water for 16 weeks. The deregulation of the Wnt/β-catenin signaling pathway and the expression of cyclooxygenase (COX)-2 have been implicated in colorectal tumorigenesis.β-Catenin and COX-2 expressions were analysed using the quantitative RT-PCR and Western blotting. Herein, we reported that the administration of IP₆markedly suppressed the incidence of tumors when compared to the control. Interestingly, the administration of IP₆had also markedly decreasedβ-catenin and COX-2 in colon tumors. Thus, the downregulation ofβ-catenin and COX-2 could play a role in inhibiting the CRC development induced by IP₆and thereby act as a potent anticancer agent.

Momordica charantiaLinn., commonly known as bitter gourd, has many protective roles due to its medicinal value as it contains bioactive components. However, this extract showed possible toxicity effect on zebrafish embryo. Thus this study was designed to differentiate the toxicity activities in two types ofM. charantiasample which are Indian and ChineseM. charantia, as well as to compare between two different aqueous extraction methods, hot and cold aqueous method, using zebrafish embryo assay assessment. It was observed that the survival rate of zebrafish embryo decreased as the concentration of test extract increased for all samples ofM. charantia. The LC₅₀values of hot aqueous ChineseM. charantia, hot aqueous IndianM. charantia, and cold aqueous ChineseM. charantiawere 144.54μg/ml, 199.53μg/ml, and 251.19μg/ml, respectively. However, cold aqueous IndianM. charantiahas a higher LC₅₀which was not in the range of the tested concentration. Hatchability ofDanio rerioembryo reduced as the concentration ofM. charantiaextract increased while no hatching was observed in the highest concentration (1000μg/ml). Scoliosis of zebrafish larvae was only seen in higher concentrations (125-1000μg/ml) of extract. The heartbeat of zebrafish larvae treated withM. charantiaextract was within the normal range, 120-180 bpm, but at higher concentrations (125-1000μg/ml) the heartbeat differed for all samples of test extract. Hence, although this plant extract was safe to be consumed due to its pharmaceutical effect, it still exhibited mild toxicity effect at higher concentration when it was evaluated on zebrafish embryo.

Epigallocatechin-3-gallate (EGCG) is the most abundant bioactive polyphenolic compound among the green tea constituents and has been identified as a potential anticancer agent in colorectal cancer (CRC) studies. This study was aimed to determine the mechanism of actions of EGCG when targeting the endoplasmic reticulum (ER) stress pathway in CRC. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was performed on HT-29 cell line and normal cell line (3T3) to determine the EGCG toxicity. Next, western blot was done to observe the expression of the related proteins for the ER stress pathway. The Caspase 3/7 assay was performed to determine the apoptosis induced by EGCG. The results demonstrated that EGCG treatment was toxic to the HT-29 cell line. EGCG induced ER stress in HT-29 by upregulating immunoglobulin-binding (BiP), PKR-like endoplasmic reticulum kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha subunit (eIF2α), activating transcription 4 (ATF4), and inositol-requiring kinase 1 alpha (IRE1α). Apoptosis was induced in HT-29 cells after the EGCG treatment, as shown by the Caspase 3/7 activity. This study indicates that green tea EGCG has the potential to inhibit colorectal cancer cells through the induction of ER stress.