Adiponectin Receptor Agonist Suppresses Human Colorectal Cancer.

BACKGROUND/AIM: Colorectal cancer (CRC) was the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide in 2022. Despite advances in oncology, CRC prognosis and treatment outcomes have shown limited improvement over the past decades, highlighting the urgent need for more effective therapies. Adiponectin signaling, known for its tumor-suppressive role in various cancers including CRC, presents a promising therapeutic target. AdipoRon, an adiponectin receptor agonist, may offer a novel strategy by restoring this signaling pathway.

MATERIALS AND METHODS

The anti-cancer effects of AdipoRon were evaluated using assays for cell viability, crystal violet staining, cell migration, apoptosis, and cell cycle distribution. Protein expression levels of AMPKα, phosphorylated AMPKα (pAMPKα), and STAT3 were assessed western blotting.

RESULTS

AdipoRon significantly inhibited HCT116 colorectal cancer cell proliferation under both low and high-density conditions in a dose-dependent manner. It also reduced cell migration. Treated cells exhibited an increased tendency toward apoptosis and a significant accumulation in the G phase of the cell cycle, accompanied by reduced proportions in the S and G/M phases. Furthermore, AdipoRon induced AMPKα phosphorylation and down-regulated the oncogenic protein STAT3.

CONCLUSION

AdipoRon effectively inhibited CRC cell proliferation and migration , effects that were associated with the up-regulation of the tumor suppressor protein pAMPKα and suppression of STAT3. These findings support the potential of AdipoRon as a promising therapeutic agent for CRC.