Source: https://onlinelibrary.wiley.com/doi/full/10.1002/fsn3.1439
In this study, the researchers investigated the effects of honokiol, a bioactive compound found in Magnolia officinalis, on the migration and invasion of H1299 lung cancer cells. Metastasis, the spread of cancer cells from the primary tumor to other parts of the body, is a major contributor to the high mortality rate in lung cancer.
The researchers focused on the role of matrix metalloproteinases (MMPs), specifically MMP-9, in promoting cancer cell migration and invasion by degrading the extracellular matrix (ECM). They hypothesized that honokiol might suppress lung cancer metastasis by targeting MMPs.
The results showed that noncytotoxic concentrations of honokiol treatment suppressed the migration and invasion ability of H1299 lung cancer cells. Importantly, honokiol specifically inhibited the proteolytic activity of MMP-9, but not MMP-2, in these cells.
Further investigation revealed that honokiol-mediated inhibition of MMP-9 expression was not due to a suppression of transcription but rather through the promotion of MMP-9 protein degradation. The researchers found that honokiol treatment led to the accumulation of acetyl-α-tubulin, a substrate of histone deacetylases 6 (HDAC6). This accumulation suggested that honokiol might affect the activity of HDAC6.
Interestingly, the researchers observed that honokiol treatment resulted in the dissociation of MMP-9 from hyper-acetylated heat shock protein 90 (Hsp90), a chaperone protein that stabilizes MMP-9. Consequently, MMP-9 underwent degradation in the presence of honokiol.
To further elucidate the role of HDAC6 in honokiol’s effects, the researchers performed experiments where they overexpressed HDAC6 in H1299 lung cancer cells. They found that HDAC6 overexpression rescued the honokiol-induced suppression of MMP-9 expression and invasion ability.
Based on these findings, the researchers concluded that honokiol inhibits the migration and invasion of lung cancer cells by suppressing the interaction between HDAC6 and Hsp90, leading to the degradation of MMP-9. This study provides insights into the potential of honokiol as a therapeutic strategy for suppressing lung cancer metastasis through epigenetic regulation.
