Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Korea.
Eco system Lab., LOCORICO, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Korea.
Molecules. 2019 Mar 7;24(5):929. doi: 10.3390/molecules24050929.
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.
恶性黑色素瘤是最致命的皮肤癌类型，且对化疗高度耐药。蜂毒肽（BV）是一种含 26 个氨基酸残基的两亲性肽，是其主要活性成分。尽管已知蜂毒肽具有多种生物学活性，如抗炎、抗菌和抗癌作用，但它对黑色素瘤的作用及其潜在的分子机制尚未完全阐明。在本研究中，我们研究了 BV 和蜂毒肽对包括 B16F10、A375SM 和 SK-MEL-28 在内的各种黑色素瘤细胞的抑制作用和作用机制。BV 和蜂毒肽强烈抑制黑色素瘤细胞的生长、集落形成存活、迁移和侵袭。它们还减少了 MSH 刺激的黑色素瘤细胞中黑色素的形成。此外，BV 和蜂毒肽通过增强 caspase-3 和 -9 的活性诱导黑色素瘤细胞凋亡。此外，我们证明了 BV 和蜂毒肽的抗黑色素瘤作用与下调 PI3K/AKT/mTOR 和 MAPK 信号通路有关。我们还发现，与单独使用蜂毒肽或 TMZ 相比，蜂毒肽与化疗药物替莫唑胺（TMZ）联合使用可显著增加对黑色素瘤细胞生长和侵袭的抑制作用。总之，这些结果表明蜂毒肽可能具有预防和治疗恶性黑色素瘤的潜力。
