# HJP 272, an endothelin receptor antagonist, and its role in cancer cell migration and invasion

## TL;DR

HJP 272, a drug that blocks endothelin receptors, reduces cancer cell movement and growth in specific cell types, suggesting potential for treating cancer spread.

## Contribution

This is the first study to explore HJP 272's anti-cancer effects, particularly in inhibiting migration and invasion in lung and breast cancer cells.

## Key findings

- HJP 272 inhibits migration, invasion, and clonogenesis in A549 and MDA-MB-231 cancer cells.
- HJP 272 reduces expression of CDK-Rb-E2F axis and IL-17 pathway genes in cancer cells.
- HJP 272 inhibits MDA-MB-231 spheroid growth but not A549 spheroid growth.

## Abstract

•HJP 272 inhibits migration, invasion and clonogenesis of A549 and MDA-MB-231 cells.•HJP 272 decreases expression of CDK-Rb-E2F axis genes in A549 cells.•HJP 272 decreases expression of IL-17 pathway genes in MDA-MB-231 cells.•HJP 272 decreases expression of and extracellular matrix genes in MDA-MB-231 cells.•HJP 272 inhibits MDA-MB-231 spheroid growth.

HJP 272 inhibits migration, invasion and clonogenesis of A549 and MDA-MB-231 cells.

HJP 272 decreases expression of CDK-Rb-E2F axis genes in A549 cells.

HJP 272 decreases expression of IL-17 pathway genes in MDA-MB-231 cells.

HJP 272 decreases expression of and extracellular matrix genes in MDA-MB-231 cells.

HJP 272 inhibits MDA-MB-231 spheroid growth.

Endothelins (ETs) are a family of versatile peptides composed of 21 amino acids with three isoforms: ET-1, ET-2, and ET-3. As the most abundant of the three isoforms, ET-1 is involved in various biological processes, such as regulation of vascular tone, humoral homeostasis, and neural crest development. However, focus is now being directed towards investigating the functions of the ET axis in the progression of different tumor types including ovarian, prostate, breast, lungs etc. HJP 272 is a novel ETAR antagonist and while our group has previously researched its effects on lung inflammation and preterm birth, this study marks the first time its role in cancer has been explored.

We evaluated the in vitro activities of HJP 272 in the ET-1 and ETAR overexpressing cell lines MDA-MB-231 (TNBC), and A549 (NSCLC). While HJP 272 had no effect on the viability of cancer cells, we observed a significant inhibition in the migration, invasion, and clonogenic capacities of both cell lines. RNA-seq and western blot data demonstrate the potential underlying molecular mechanisms of this compound in vitro. Furthermore, HJP 272 was evaluated in a 3D spheroid assay for its ability to inhibit tumor formation in both cell lines, revealing a significant change in MDA-MB-231 cells while no significant changes were observed in A549 cells.

Our work indicates a therapeutic potential for HJP 272 in cancer metastasis. The distinct outcomes between the two cell lines shed light on the potential differences of HJP 272′s effects across multiple cancer types.