Abstract
Malignant melanoma is the deadliest form of skin cancer and highly chemoresistant. Melittin, an amphiphilic peptide containing 26 amino acid residues, is the major active ingredient from bee venom (BV). Although melittin is known to have several biological activities such as anti-inflammatory, antibacterial and anticancer effects, its antimelanoma effect and underlying molecular mechanism have not been fully elucidated. In the current study, we investigated the inhibitory effect and action mechanism of BV and melittin against various melanoma cells including B16F10, A375SM and SK-MEL-28. BV and melittin potently suppressed the growth, clonogenic survival, migration and invasion of melanoma cells. They also reduced the melanin formation in α-melanocyte-stimulating hormone (MSH)-stimulated melanoma cells. Furthermore, BV and melittin induced the apoptosis of melanoma cells by enhancing the activities of caspase-3 and -9. In addition, we demonstrated that the antimelanoma effect of BV and melittin is associated with the downregulation of PI3K/AKT/mTOR and MAPK signaling pathways. We also found that the combination of melittin with the chemotherapeutic agent temozolomide (TMZ) significantly increases the inhibition of growth as well as invasion in melanoma cells compared to melittin or TMZ alone. Taken together, these results suggest that melittin could be potentially applied for the prevention and treatment of malignant melanoma.
Highlights
Melanoma, a malignant tumor of melanocytes, is the most rapid and fatal form of skin cancer [1,2].The onset of malignant melanoma has been reported to be influenced by various environmental and genetic factors including ultraviolet (UV) light and oncogenic BRAF mutations, respectively [3,4].Melanoma can spread to other parts of the body, making treatment more difficult and causing death
To determine whether bee venom (BV) and melittin affect melanoma cell growth, B16F10, A375SM and SKSK-MEL-28 cells were treated with various concentrations (0–100 μg/mL) of BV and melittin for 72 h, MEL-28 cells were treated with various concentrations (0–100 μg/mL) of BV and melittin for 72 h, and the MTT assay was performed
We demonstrated that BV and its main component melittin potently suppress multiple oncogenic processes including growth, clonogenicity, migration, invasion and melanogenesis in malignant melanoma cells
Summary
A malignant tumor of melanocytes, is the most rapid and fatal form of skin cancer [1,2].The onset of malignant melanoma has been reported to be influenced by various environmental and genetic factors including ultraviolet (UV) light and oncogenic BRAF mutations, respectively [3,4].Melanoma can spread to other parts of the body, making treatment more difficult and causing death. A malignant tumor of melanocytes, is the most rapid and fatal form of skin cancer [1,2]. The onset of malignant melanoma has been reported to be influenced by various environmental and genetic factors including ultraviolet (UV) light and oncogenic BRAF mutations, respectively [3,4]. Melanoma can spread to other parts of the body, making treatment more difficult and causing death. Over the past 30 years, numerous therapies have been developed, but the prognosis for patients with malignant melanoma has not been improved significantly, with an average survival time of 6–9 months. The primary treatment for melanoma is surgical removal of the tumor or chemotherapy, but the treatment is incomplete and the patient’s prognosis is poor due to recurrence [5,6].
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