The Suppression of Signal Transducer and Activator of Transcription-3 in A549 human Lung Carcinoma Cells Induced by Marine Sponge Callyspongia aerizusa.

Abstract

Introduction: Lung cancer is recognized as a highly lethal disease, demanding swift and accurate solutions. Previous analysis showed the cytotoxic impact of Callyspongia aerizusa (C. aerizusa) extract containing ergost-22-en-3-one and ergost-7-en3-ol against A549 lung cancer cells, with an IC₅₀ value of 9.38 μg/mL. However, the extract did not have cytotoxicity towards Het-1A esophagus epithelial cells. Several reviews also validated the upregulation of pro-apoptotic molecules and the inhibition of anti-apoptotic molecules linked to the caspase-dependent signaling pathway.

Purpose: The objective of this research was to extend the understanding of the effects of C. aerizusa extract on A549 lung carcinoma, examining its influence on various signaling pathways, malignancy, migration, and invasion.

Materials and methods: PCR was used to measure mRNA expression, targeting PTEN, Akt, mTOR, STAT-3, IL-6, VEGF, and HIF1α. Additionally, Western Blot analysis was adopted to assess PTEN, p-Akt, Akt, p-mTOR, and p-STAT-3 protein expressions. Wound healing and invasion assays were performed to measure the migration and invasion capabilities of A549 cells post-treatment with C. aerizusa extract.

Results: The mRNA expression analysis showed an increase in Akt and m-TOR but a decrease in PTEN and STAT-3 after 24 hours of treatment with C. aerizusa extract. At the protein level, there was a downregulation of p-Akt, Akt, p-mTOR, and p-STAT-3, while PTEN increased during 24-hour treatment. Wound healing and invasion assay results showed a weakened ability of A549 cells after a 24-hour treatment with C. aerizusa extract. Moreover, IL-6 and HIF-1α mRNA expression levels decreased during 24 hours, while VEGF mRNA had a slight decrease compared to untreated cells.

Conclusion: In conclusion, the ergosteroids present in marine sponge C. aerizusa extract signified a remarkable reduction in malignancy, migration, and invasion capabilities in A549 lung carcinoma cells. These results suggested their promising candidacy for future anti-angiogenesis in anticancer therapy.