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Analysing the molecular mechanisms of cell migration inhibition in response to honokiol

Lei, Ying

Authors

Ying Lei



Abstract

Malignant melanoma is the leading cause of skin cancer-induced death worldwide. Current therapies for treating melanoma patients are limited by rapid resistance to treatments and thus alternative anti-cancer drugs with high efficiency are urgently required. Honokiol is a natural compound isolated from the Magnoliaceae family with potent anti-cancer effects. However, the exact molecular mechanisms underpinning the anti-cancer effects of honokiol remain poorly defined. This study demonstrated that honokiol reduced cell viability, affected metabolic activities, inhibited cellular migration, promoted apoptotic effects and induced morphological alterations in the highly metastatic melanoma cell line, A375. Comprehensive qRT-PCR and immunoblotting analyses indicated that honokiol upregulated the expression of kisspeptin (KISS1) and its receptor, KISS1R, suggesting that KISS1 / KISS1R signalling pathway might be one of the molecular mechanisms targeted by honokiol. This study further revealed that honokiol-mediated KISS1 / KISS1R signalling pathway downregulated VEGF-A and MMP-2 transcription, upregulated the mRNA expression of MMP-9 and TIMP-4, but not NF-κB. Furthermore, treatment with kisspeptin 10, with or without honokiol has been demonstrated to alter the mRNA expression of KISS1, KISS1R, MMP-9, MMP-2, TIMP-4 and VEGF-A, but not NF-κB. This study suggests that KISS1 / KISS1R signalling pathway may be involved in honokiol-modulated anti-metastatic effects in human A375 melanoma cells, and that honokiol could be considered as a natural agent against skin cancer.

Thesis Type Thesis
Deposit Date Mar 31, 2022
Publicly Available Date Mar 31, 2022
DOI https://doi.org/10.17869/enu.2022.2859871
Public URL http://researchrepository.napier.ac.uk/Output/2859871
Award Date Oct 28, 2021

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