Journal
ANTIBIOTICS-BASEL
Volume 9, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/antibiotics9080517
Keywords
melittin; Apis florea; malignant melanoma; apoptosis; F-actin; epidermal growth factor receptor
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Funding
- Research and Researchers for Industries (RRi) from the Thailand Science Research and Innovation (TSRI) [PhD59I0055]
- National Research Council of Thailand (NRCT)
- Research Center in Bioresources for Agriculture, Industry, and Medicine, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand
- Graduate School, Chiang Mai University, Chiang Mai, Thailand
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Melittin, a major component found in bee venom, is produced by theApisspecies of the honey bee. In this study, the effect of melittin derived fromApis florea(Mel-AF), which is a wild honey bee species that is indigenous to Thailand, was investigated against human malignant melanoma (A375) cells. In this study, Mel-AF exhibited considerable potential in the anti-proliferative action of A375 cells. Subsequently, the cellular mechanism of Mel-AF that induced cell death was investigated in terms of apoptosis. As a result, gene and protein expression levels, which indicated the activation of cytochrome-c release and caspase-9 expression, eventually triggered the release of the caspase-3 executioner upon Mel-AF. We then determined that apoptosis-mediated cell death was carried out through the intrinsic mitochondrial pathway. Moreover, advanced abilities, including cell motility and invasion, were significantly suppressed. Mel-AF manipulated the actin arrangement via the trapping of stress fibers that were found underneath the membrane, which resulted in the defective actin cytoskeleton organization. Consequently, the expression of EGFR, a binding protein to F-actin, was also found to be suppressed. This outcome strongly supports the effects of Mel-AF in the inhibition of progressive malignant activity through the disruption of actin cytoskeleton-EGFR interaction and the EGFR signaling system. Thus, the findings of our current study indicate the potential usefulness of Mel-AF in cancer treatments as an apoptosis inducer and a potential actin-targeting agent.
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