Paolino Giovanni, Di Nicola Matteo Riccardo, Raggi Carla, Camerini Serena, Casella Marialuisa, Pasquini Luca, Zanetti Cristiana, Russo Vincenzo, Mercuri Santo Raffaele, Lugini Luana, Federici Cristina
Unit of Dermatology and Cosmetology, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy.
Faculty of Medicine and Surgery, Università Vita-Salute San Raffaele, 20132 Milan, Italy.
Toxins (Basel). 2025 Mar 21;17(4):152. doi: 10.3390/toxins17040152.
Research on viper venom has expanded into diverse medical applications, including cancer treatment. This study investigates the potential of venom in oncology, evaluating its cytotoxicity and chemosensitising effects on malignant melanoma cells. Proteomic analysis identified 125 proteins in the venom, with Phospholipases A2, C-type lectins, and metalloproteinases among the most abundant components. These proteins are associated with cytotoxic, anti-proliferative, and tumor-inhibiting properties. Three melanoma cell lines (M001, Me501, and A375) were used to assess venom cytotoxicity. The IC50 values demonstrated consistent venom sensitivity across cell lines (approximately 1.1 µg/mL). Combined treatment with venom and cisplatin significantly increased the cytotoxicity compared to single-agent treatments. Notably, venom enhanced the sensitivity of cisplatin in resistant cell lines (M001 and Me501), increasing cell mortality by up to 40%. The A375 cell line, inherently more sensitive to cisplatin, exhibited additional cytotoxic effects only at higher venom doses. The morphological changes observed under microscopy confirmed venom-induced cellular changes, further supporting its potential as an anti-cancer agent. The selective targeting of melanoma cells by venom components, particularly in muscle-associated metastases, suggests a unique therapeutic niche. While cisplatin was chosen for this pilot study due to its established cytotoxicity, future research will explore venom combinations with contemporary treatments such as immunotherapy and targeted therapies. Although preliminary, these findings provide a foundation for integrating venom-based strategies into advanced melanoma protocols, aiming to improve outcomes in resistant or metastatic cases.
对蝰蛇毒液的研究已扩展到多种医学应用领域，包括癌症治疗。本研究调查了毒液在肿瘤学方面的潜力，评估其对恶性黑色素瘤细胞的细胞毒性和化学增敏作用。蛋白质组学分析在毒液中鉴定出125种蛋白质，其中磷脂酶A2、C型凝集素和金属蛋白酶是含量最丰富的成分。这些蛋白质具有细胞毒性、抗增殖和肿瘤抑制特性。使用三种黑色素瘤细胞系（M001、Me501和A375）评估毒液的细胞毒性。IC50值表明各细胞系对毒液的敏感性一致（约1.1 µg/mL）。与单药治疗相比，毒液和顺铂联合治疗显著增加了细胞毒性。值得注意的是，毒液增强了顺铂对耐药细胞系（M001和Me501）的敏感性，使细胞死亡率提高了40%。A375细胞系对顺铂本来就更敏感，仅在毒液剂量较高时才表现出额外的细胞毒性作用。显微镜下观察到的形态变化证实了毒液诱导的细胞变化，进一步支持了其作为抗癌剂的潜力。毒液成分对黑色素瘤细胞的选择性靶向作用，特别是在肌肉相关转移灶中的靶向作用，提示了一个独特的治疗领域。由于顺铂已确定的细胞毒性，本初步研究选择了顺铂，但未来的研究将探索毒液与免疫疗法和靶向疗法等当代治疗方法的联合应用。尽管这些发现尚属初步，但为将基于毒液的策略纳入晚期黑色素瘤治疗方案奠定了基础，旨在改善耐药或转移性病例的治疗效果。
