OBJECTIVE: In the present review, we highlight the Notch signalling pathway components i.e. Notch receptors, ligands, effector, and their regulators. We also discuss the tumor biology of the Notch pathway involved in various cancers.
RESULTS: Interestingly, the Notch signalling pathway is dysregulated in many cancers. Notch may serve as oncogene or tumor suppressor and plays an important role in cancers of the liver, pancreas, endometrium of uterus, ovary, prostate, bladder and colon. The activation of Notch pathway plays a vital role in the progression of some cancer. In addition, Notch pathway activation was also shown to drive chemoresistance in cancer, as well. Chemotherapeutically, combined NOTCH1 inhibitor synergistically attenuated chemotherapy-enriched cancer stem cell population both in vitro and in vivo. This may prove to be beneficial in the treatment of cancer.
CONCLUSION: The Notch inhibitors possess anti-proliferative effects on cancer, thereby serving as a new treatment for cancer.
OBJECTIVE: This review was aimed to critically analyze the therapeutic viability and anticancer efficacy of Eurycoma longifolia in the treatment of cancer and also to propose its molecular and translational mechanism of cytotoxicity against cancerous cells.
RESULTS: Among a range of medicinally active compounds isolated from various parts (roots, stem, bark and leaves) of Eurycoma longifolia, 16 compounds have shown promising anti-proliferative and anticancer efficacies. Eurycomanone, one of the most active medicinal compounds of Eurycoma longifolia, displayed a strong dose-dependent anticancer efficacy against lung carcinoma (A-549 cells) and breast cancer (MCF-7 cells); however, showed moderate efficacy against gastric (MGC-803 cells) and intestinal carcinomas (HT-29 cells). The prime mode of cytotoxicity of Eurycoma longifolia and its medicinal compounds is the induction of apoptosis (programmed cell death) via the up-regulation of the expression of p53 (tumor suppressor protein) and pro-apoptotic protein (Bax) and downregulation of the expression of anti-apoptotic protein (Bcl-2). A remarkable alleviation in the mRNA expression of various cancer-associated biomarkers including heterogeneous nuclear ribonucleoprotein (hnRNP), prohibitin (PHB), annexin-1 (ANX1) and endoplasmic reticulum protein-28 (ERp28) has also been evidenced.
CONCLUSION: Eurycoma longifolia and its medicinal constituents exhibit promising anticancer efficacy and thus can be considered as potential complementary therapy for the treatment of various types of human cancers.