ABSTRACT
The G-protein-coupled estrogen receptor (GPER; G-protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as the cell type that is the potential origin of HGSC ovarian cancer (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER agonist on cell viability, providing a better understanding of the effects of this compound on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.
Subject(s)
Cell Movement , Cell Survival , Ovarian Neoplasms , Quinolines , Receptors, Estrogen , Receptors, G-Protein-Coupled , Humans , Female , Cell Movement/drug effects , Ovarian Neoplasms/pathology , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/drug therapy , Receptors, G-Protein-Coupled/agonists , Receptors, G-Protein-Coupled/metabolism , Cell Survival/drug effects , Receptors, Estrogen/metabolism , Cell Line, Tumor , Quinolines/pharmacology , Cell Proliferation/drug effects , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/metabolism , Benzodioxoles/pharmacology , CyclopentanesABSTRACT
Both cancer and cardio-metabolic disease disparities exist among specific populations in the US. For example, African Americans experience the highest rates of breast and prostate cancer mortality and the highest incidence of obesity. Native and Hispanic Americans experience the highest rates of liver cancer mortality. At the same time, Pacific Islanders have the highest death rate attributed to type 2 diabetes (T2D), and Asian Americans experience the highest incidence of non-alcoholic fatty liver disease (NAFLD) and cancers induced by infectious agents. Notably, the pathologic progression of both cancer and cardio-metabolic diseases involves innate immunity and mechanisms of inflammation. Innate immunity in individuals is established through genetic inheritance and external stimuli to respond to environmental threats and stresses such as pathogen exposure. Further, individual genomes contain characteristic genetic markers associated with one or more geographic ancestries (ethnic groups), including protective innate immune genetic programming optimized for survival in their corresponding ancestral environment(s). This perspective explores evidence related to our working hypothesis that genetic variations in innate immune genes, particularly those that are commonly found but unevenly distributed between populations, are associated with disparities between populations in both cancer and cardio-metabolic diseases. Identifying conventional and unconventional innate immune genes that fit this profile may provide critical insights into the underlying mechanisms that connect these two families of complex diseases and offer novel targets for precision-based treatment of cancer and/or cardio-metabolic disease.
Subject(s)
Diabetes Mellitus, Type 2 , Non-alcoholic Fatty Liver Disease , Prostatic Neoplasms , Male , Humans , Diabetes Mellitus, Type 2/genetics , Ethnicity , Immunity, Innate/geneticsABSTRACT
Thirty actinomycete isolates were isolated from soil and tested against Candida albicans in vitro. The active isolate was identified by 16s-rRNA gene sequencing method as Streptomyces toxytricini. The antifungal compound was extracted with ethyl acetate followed by diethyl ether. Both HPLC and GC-MS analysis confirmed presence of one pure compound in the diethyl ether extract. The compound is a yellow liquid has a maximum absorbance at 240 nm in methanol. The chemical structure was elucidated by 1D and 2D-NMR and IR analyses. The elucidated molecular formula was C36H54O14. The compound is a polyacetal tricyclononane derivative, composed of a tricyclononane ring attached from the carbon atom number four with an oligo-acetal chain (six acetal groups in chain) and from the carbon atom number seven with a methoxy carbonyl benzene-1,3-dicarboxylic acid. The purposed name is: 4- {[tricycle(3.2.1.1(1,3))non-8-yl] methoxy carbonyl benzene-1,3-dicarboxylic acid} (2,4,5,6,7,8,9 heptaoxa, 3-ethoxy, 5,6,7,9-tetramethyl unidecane).
