Skin cancer has evolved as the most common malignant disease, accounting for 4.5% of all new cancer cases. Melanoma, the most aggressive skin cancer type, develops in melanocytes and has high mortality rates due to its biological features and frequent failures of therapeutic alternatives. On the other hand, non-melanoma skin cancers (NMSC), the most common malignant tumors in humans, are developed in keratinocytes of the basal or spinous layer, and increased exposure to ultraviolet (UV) light remains the most important modifiable risk factor. To date, treatment alternatives for melanoma are limited to surgery, in cases of early diagnosis, and a few pharmacological options in inoperable tumors. These limitations for skin cancer management evidence the need to develop therapeutic options for prevention and treatment. The antiproliferative effects of Amaryllidaceae alkaloids have been tested for different types of cancer. However, their activity on skin models is not well-established. Pure alkaloids and alkaloidal fractions characterized by GC-MS of several Amaryllidaceae species from Crinum, Zephyranthes, Hippeastrum, and Eucharis genera were assayed by their effects on skin cancer. Photoprotective effects of the alkaloids and fractions were determined through cell viability assay, and the quantification of intracellular reactive oxygen species (ROS) and inflammation biomarker IL-6 in UVB-stimulated keratinocytes (HaCaT). Cytotoxicity were assessed in human metastatic melanoma cells (CRL-3229) to evaluate therapeutic potential, and chemometric techniques were used to analyze data. Most substances enhanced HaCaT proliferation at 5.0 µg/mL. E. caucana and Z. carinata bulbs alkaloidal fractions significantly reduced intracellular ROS and IL-6 production in UVB-stimulated HaCaT, respectively. Tazettine and lycoramine showed photoprotective effects. Additionally, E. caucana bulbs alkaloidal fraction was selectively cytotoxic in melanoma cells at 20.0 µg/mL. Collectively, these results demonstrate that Amaryllidaceae alkaloids could represent a new option in skin cancer management, acting as photoprotective agents in healthy UVB-exposed keratinocytes and therapeutic agents in melanoma.
展开▼
机译：皮肤癌已经发展成为最常见的恶性疾病，占所有新癌症病例的4.5％。黑色素瘤，最具侵略性的皮肤癌型，在黑素细胞中发展，并且由于其生物学特征和频繁的治疗方法失败而具有高的死亡率。另一方面，非黑色素瘤皮肤癌（NMSC），人类中最常见的恶性肿瘤，在基底或棘塔的角质形成细胞中开发，并且增加了暴露于紫外线（UV）光仍然是最重要的可改性风险因素。迄今为止，在早期诊断的情况下，黑素瘤的治疗方法仅限于手术，以及少量可操作的肿瘤中的药理学选择。这些皮肤癌症管理的限制证据是需要制定预防和治疗的治疗方案。对不同类型的癌症进行了测试的氨基薄膜生物碱的抗增殖作用。然而，他们对皮肤模型的活动不是很好的。通过它们对皮肤癌的影响来测定来自Crinum，Zephylanthes，Hippeasstrum和Eucharis属的几种来自牛桂膜的GC-MS的纯生物碱和组分馏分。通过细胞活力测定法测定生物碱和级分的光保护作用，并在UVB刺激的角质形成细胞（HACAT）中的细胞内反应性氧物质（ROS）和炎症生物标志物IL-6的定量。在人转移性黑色素瘤细胞（CRL-3229）中评估细胞毒性以评估治疗潜力，并使用化学计量技术来分析数据。大多数物质增强了5.0和微量的HaCat增殖; G / ml。 E. Caucana和Z.Carinata灯泡分别在UVB刺激的HACAT中显着降低了细胞内ROS和IL-6产生。 Tazettine和Lycoramine显示出光保护作用。另外，E. Caucana灯泡生物馏分在20.0微米的黑色素瘤细胞中选择性细胞毒性; G / ml。总的来说，这些结果表明，Amaryllidaceae生物碱可以代表皮肤癌管理中的一种新选择，其作为黑色素瘤的健康UVB暴露的角质形成细胞和治疗剂中的光保护剂。
展开▼
