All-trans retinoic acid (ATRA) is an active metabolite of vitamin A under the family retinoid. Retinoids, through their cognate nuclear receptors, exert potent effects on cell growth, differentiation and apoptosis, and have significant promise for cancer therapy and chemoprevention. Differentiation therapy with ATRA has marked a major advance and become the first choice drug in the treatment of acute promyelocytic leukemia (APL). Conversions of 13-cis-retinoic acid and 9-cis-retinoic acid to all-trans-retinoic acid is very rapid. Currently, two distinct families of retinoid responsive nuclear receptors have been identified and characterized: retinoic acid receptors (RARs) and retinoid receptors (RXRs), each of which include three isoforms, α,β,and γ. ATRA is being increasingly included in anti-tumour therapeutical schemes for the treatment of various tumoral diseases such as Kaposi's sarcoma, head and neck squamous cell carcinoma, ovarian carcinoma, bladder cancer, neuroblastoma and has shown antiangiogenic effects in several systems, inhibiting proliferation in vascular smooth muscle cells (VSMCs) and anti-inflammatory in rheumatoid arthritis. This review helps to understand in details about the ATRA and its role on cancer and it is predicted that modulating the activity of ATRA will soon provide novel prevention and treatment approaches for the cancer patients.
Lysyl oxidases (LysOX; EC 1.4.3.13, protein-lysine 6-oxidases) are extracellular copper enzymes that catalyze the cross-linking of collagens or elastin in the extracellular matrix (ECM), thereby regulating the tensile strength of tissues. Recent implication of LysOX in cancer, wound healing, cell motility, chemotaxis, and differentiation reflects its remarkable functional diversity and also in the central nervous system pathologies. However, recent reports also demonstrated novel roles for LysOX, including the ability to regulate gene transcription, motility/migration, and cell adhesion. These diverse functions have led researchers to hypothesize that LysOX may have multiple roles affecting both extra- and intracellular cell function(s). Both down and up-regulation of LysOX in tumor tissues and cancer cell lines have been described, suggesting a dual role for LysOX as a tumor suppressor, as well as a metastasis promoter gene. In this review we explain in detail the role of lysyl oxidase in tumor progression and metastasis.
The purpose of this study was to investigate whether all-trans retinoic acid (ATRA) has antioxidant property. The study was also focused on its inhibitory effect on the acute and chronic inflammation and tumor-associated capillary formation in terms of angiogenesis in C57BL/6 mice after incorporated in liposome composed of distearoylphosphatidylcholine (DSPC/cholesterol). ATRA possesses a number of important biologic activities including oncostatic, antioxidant and immunostimulatory actions. Our study was designed to evaluate the antioxidant activity of free ATRA by nitric oxide scavenging, superoxide radical scavenging, hydroxyl radical scavenging and lipid peroxide scavenging assays. The ATRA showed significant scavenging activities in all these antioxidant assays comparable to the standard antioxidant. We have also evaluated the activity of encapsulated ATRA against anti-inflammatory activity in C57BL/6 mice. The paw oedema inhibition was found in carrageenan model as 55.56% and 66.67% for free ATRA and encapsulated ATRA treatment respectively and for formaldehyde model it was found to be 60.87% and 69.57% respectively compared with saline treated control mice. Encapsulated ATRA inhibited the tumor-associated capillary formation in mice induced by highly metastatic B16F10 melanoma cells significantly than the free ATRA did. In this study the inhibition of tumor-directed capillary formation was found to be 56.25% and 62.50% for free ATRA and encapsulated ATRA treatment respectively. In conclusion, ATRA showed a significant antioxidant property in vitro. Free ATRA has anti-inflammatory activity as proved by us in animal model of acute and chronic inflammation and antiangiogenesis activity. Furthermore, its activity was boosted by encapsulation in liposome.
The Nm23 gene is a metastatic suppressor identified in a melanoma cell line and expressed in different tumors where their levels of expression are associated with reduced or increased metastatic potential. Nm23 is one of the over 20 metastasis suppressor genes (MSGs) confirmed in vivo. It is highly conserved from yeast to human, implying a critical developmental function. Tumors with alteration of the p53 gene and reduced expression of the Nm23 gene are more prone to metastasis. Nm23-H1 has 3'-5' exonuclease activity. This review focuses on the role of Nm23 in cancer progression and also a potential novel target for cancer therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.