Table 2.
Relevant leptin antagonists that have been exhibited to prevent aggressive tumor behavior
| Authors/Tissue | Antagonist used | Experimental design | Major observations |
|---|---|---|---|
| Bain et al. 2014 [111] Gastroesophageal adenocarcinomas (clinical samples) as well as in vitro experiments on gastric cancer cells and esophageal cancer cells. |
Recombinant super human leptin antagonist (SHLA), which is a polypeptide chain containing 146 amino acids. | Cisplatin-resistant gastric cancer cell-line AGS Cis5 and esophageal adenocarcinoma cell-line OE33 were used. Originally, AGS cell-line was derived from a gastric adenocarcinoma of a Caucasian female. In a 96-well plate, cells were grown. Cisplatin and/or SHLA were added. Following incubation, MTT cell proliferation assay was performed. | Leptin antagonist SHLA increased the sensitivity of AGS Cis5 and OE33 cell-lines to cisplatin. SHLA inhibited the growth of OE33 cells when given alone. In both AGS Cis5 and OE33, SHLA inhibited leptin-induced cell proliferation. |
| Trevellin et al. 2015 [101] Esophageal adenocarcinoma patients, and in vitro study on esophageal adenocarcinoma cells. |
Super human leptin antagonist (SHLA). | Treatment of OE33 cells with conditioned media (CM) collected from cultured biopsies of adipose tissue and peritumoral adipose tissue of patients with lymph node metastasis. | After treatment with CM, mRNA levels of two key EMT regulator genes, alpha-smooth muscle actin (α-SMA) and E-cadherin, were increased. However, SHLA diminished the mRNA expression of α-SMA and E-cadherin. |
| Catalano et al. 2015 [112] In vitro and in vivo experimental models using ERα-positive (MCF-7) and -negative (SK-BR-3) breast cancer cells. |
Pegylated LDFI (LDFI-PEG): polyethylene glycol (PEG)-attached to tetrapeptide that mimics the sequence of leptin binding site I. Leptin interacts with Ob-R through 3 different binding sites: I–III. Site I is crucial for the formation of an active leptin–Ob-R complex and in its subsequent activation. Amino acids 39–42 (Leu-Asp-Phe-Ile-LDFI) were shown to contribute to leptin binding site I. | Injected SK-BR-3 breast cancer cells into the intrascapular region of female nude mice (nu/nu Swiss) and followed tumor growth after administration of LDFI-PEG. | After LDFI-PEG treatment, tumor volumes continued to reduce over control for the duration of experiment. At the end of treatment (28 days) it was observed that PEG-LDFI induced a significant tumor growth inhibition compared to vehicle-treated mice. Sections of tumors from PEG-LDFI-treated mice exhibited a reduction in the expression of proliferation marker Ki-67, and phosphorylated levels of STAT3, MAPK and AKT than controls. |
AKT: Protein kinase B/a serine/threonine kinase, EMT: Epithelial-mesenchymal transition, MAPK: Mitogen-activated protein kinase, STAT3: Signal transducer and activator of transcription 3