Therapeutic targeting of oncogenic transcription factors by natural products in eye cancer

Abstract

Carcinogenesis has a multifactorial etiology, and the underlying molecular pathogenesis is still not entirely understood, especially for eye cancers. Primary malignant intraocular neoplasms are relatively rare, but delayed detection and inappropriate management contribute to poor outcomes. Conventional treatment, such as orbital exenteration, chemotherapy, or radiotherapy, alone results in high mortality for many of these malignancies. Recent sequential multimodal therapy with a combination of high-dose chemotherapy, followed by appropriate surgery, radiotherapy, and additional adjuvant chemotherapy has helped dramatically improve management. Transcription factors are proteins that regulate gene expression by modulating the synthesis of mRNA. Since transcription is a dominant control point in the production of many proteins, transcription factors represent key regulators for numerous cellular functions, including proliferation, differentiation, and apoptosis, making them compelling targets for drug development. Natural compounds have been studied for their potential to be potent yet safe chemotherapeutic drugs. Since the ancient times, plant-derived bioactive molecules have been used to treat dreadful diseases like cancer, and several refined pharmaceutics have been developed from these compounds. Understanding targeting mechanisms of oncogenic transcription factors by natural products can add to our oncologic management toolbox. This review summarizes the current findings of natural products in targeting specific oncogenic transcription factors in various types of eye cancer.

Citrus fruits intake and oral cancer risk: A systematic review and meta-analysis

“…In the last two decades, numerous pre-clinical studies have documented the anti-proliferative activity of flavonoids, which has been largely linked to their abilities to interact with specific intracellular signalling pathways, in addition to their well-known antioxidant capacity (57,(59)(60)(61)(62)(63)(64). In this field, recently, we have reported the anti-cancer activity of Citrus bergamia (bergamot) juice (BJ) in different in vitro (65,66) and in vivo (67) models, and have proposed that its flavonoid content is responsible for this action (68).…”

High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery

“…Mechanism-informed phenotypic screening is one of the newer strategies for antibacterial HTS assays, the most common of which is a reporter gene assay that reports the signaling pathways with which the hits are interacting [ 35 , 36 ]. However, a reporter gene assay demonstrates if a molecule is working against a specific pathway for which the molecular target needs to be known, which can have spatial and structural differences from strain to strain [ 37 ].…”

The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms

“…While primary intraocular cancers are relatively rare diseases, delayed diagnosis and inadequate therapy result in a poor prognosis, and the condition can be fatal if left untreated. Eye cancers, as well as carcinogenesis, have a multifactorial etiology, and a complex molecular pathogenesis that remains unclear [34]. Nevertheless, MMPs, especially the gelatinases MMP-2 and MMP-9, have a significant role in the development and progression of cancers, including those of the colon, lung, prostate, and breast.…”

“…One of the most common intraocular cancers in adults is uveal melanoma (UM), which forms from neuroectodermal melanocytes in the choroid, ciliary body, and iris. Moreover, metastases in the liver are often detected in the course of UM [34]. Its development may be strongly influenced by MMP and TIMP levels: Immunohistochemical studies have found MMP-1, -2, -9, and -19, membrane-type 1-MMP and physiological inhibitors of MMPs (TIMP-2 and -3) to have a heterogeneous distribution and intensity consistent with regional differences in the tumor microenvironment [36].…”