Leptin signaling and apoptotic effects in human prostate cancer cell lines

Abstract

Leptin can clearly induce apoptosis in human PCa cell lines. These findings could lead to development of new leptin agonists with enhanced pro-apoptotic effects and targeted for use in human PCa.

The Adipocyte-Derived Hormone Leptin Has Proliferative Actions on Androgen-Resistant Prostate Cancer Cells Linking Obesity to Advanced Stages of Prostate Cancer

“…In these studies, they induced apoptosis in the cells using starvation medium for 48 hrs. The proapoptotic response to leptin in this study was rapid and sensitive, being maximal already with 1 ng/mL and 6 hrs of exposure [40]. The proapoptotic effect of leptin was maintained in all cell lines for up to 24 hrs, and then mostly reduced by 72 hrs [40].…”

“…The proapoptotic response to leptin in this study was rapid and sensitive, being maximal already with 1 ng/mL and 6 hrs of exposure [40]. The proapoptotic effect of leptin was maintained in all cell lines for up to 24 hrs, and then mostly reduced by 72 hrs [40]. As possible explanation for these conflicting results concerning the apoptosis, in can be presumed the ability of leptin to variously affect the balance between pro- and antiapoptotic signals, depending on the cell type, dose of leptin treatment, and the pathophysiological and molecular milieu active at a given point in time [20–22, 40].…”

“…As a matter of fact, it seems that leptin effects on apoptosis in prostate cancer cells continue to be a subject for serious debate, as also some very conflicting results are available now in the literature. For instance, Samuel-Mendelsohn et al reported very recently their surprising finding that leptin exerted proapoptotic effects in four PCa cell lines (PC3, DU145, PC3/AR and LNCaP), as assessed by four different parameters of apoptosis [40]. In these studies, they induced apoptosis in the cells using starvation medium for 48 hrs.…”

Association of Leptin Receptor Lys109Arg and Gln223Arg Polymorphisms with Increased Risk of Clear Cell Renal Cell Carcinoma

“…Leptin also is an important tumor cell growth factor. Several studies have demonstrated that leptin stimulates endothelial cell proliferation and angiogenesis, inhibits apoptosis gene and protein expression in cell lines (Samuel-Mendelsohn et al, 2011;Ptak et al, 2013;Wu et al, 2013;Yuan et al, 2013). Leptin exerts its biological functions through binding to the extracellular domain of LEPR.…”

The molecular mechanism of action of superactive human leptin antagonist (SHLA) and quadruple leptin mutein Lan-2 on human ovarian epithelial cell lines

“…Another leptin antagonist LDFI (leptin binding site I) also inhibits leptin-stimulated proliferation of breast cancer cells, MCF-7 and SKBR-3 [16]. Lan-1 has been shown to inhibit leptin signalling in the prostate cancer cell line LNCaP [17]. Bain et al [18] have shown that superactive human leptin antagonist (SHLA) alone or in combination with cisplatin is a potential anticancer agent in gastro-oesophageal adenocarcinomas.…”