Liver X receptors and estrogen receptor ß, two players in a rare subtype of NSCLC.

Liver X receptors (LXRαß) play essential roles in the maintenance of the normal functions of macrophages, in modulation of immune system responses and cholesterol homeostasis. We have reported that LXRαß-/- mice develop squamous cell lung cancer. We now report that those LXRαß-/- mice, which live to 18-months of age, spontaneously develop a second type of lung cancer resembling a rare subtype of NSCLC (TTF-1 and P63-positive). The lesions are characterized as follows: a high proliferation rate; a marked accumulation of abnormal macrophages; an increase in the number of regulatory T cells; a remarkably low level of CD8+ cytotoxic T lymphocytes; enhanced TGFß signaling; an increased expression of matrix metalloproteinases accompanied by degradation of lung collagen; and a loss of estrogen receptor ß (ERß). Because NSCLC is associated with cigarette smoking, we investigated the possible links between loss of LXRαß and CS. A Kaplan-Meier Plotter database revealed reduced expression of LXRαß and ERß was correlated with low overall survival (OS). Thus, reduction of LXRαß expression by cigarette smoking may be one mechanism through which CS causes lung cancer. The possibility that maintenance of LXRαß and ERß signaling could be used in the treatment of NSCLC needs further investigation.

Synergistic effects of curcumin and its analogs with other bioactive compounds: A comprehensive review.

Curcumin, as a natural compound, extracted from plant Curcuma longa, is abundant in the Indian subcontinent and Southeast Asia, and have been used in a diverse array of pharmacological activities. Although curcumin has some limitations like low stability and low bioavailability, it has been proved that this compound induced apoptosis signaling and is also known to block cell proliferation signaling pathway. Recently, extensive research has been carried out to study the application of curcumin as a health improving agent, and devise new methods to overcome to the curcumin limitations and incorporate this functional ingredient into foods. Combinational chemotherapy is one of the basic strategies is using for 60 years for the treatment of various health problems like cancer, malaria, inflammation, diabetes and etc. Molecular hybridization is another strategy to make multi-pharmacophore or conjugated drugs with more synergistic effect than the parent compounds. The aim of this review is to provide an overview of the pharmacological activity of curcumin and its analogs in combination with other bioactive compounds and cover more recent reports of anti-cancer, anti-malarial, and anti-inflammatory activities of these analogs.