Department of Drug Sciences, University of Catania, Via S. Sofia 64, 95125, Catania, Italy.
Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Via S. Sofia, 89, 95123, Catania, Italy.
Chem Biol Interact. 2019 May 25;305:79-85. doi: 10.1016/j.cbi.2019.03.029. Epub 2019 Mar 29.
Melanoma is a highly invasive cancer that resists most conventional treatments. Therefore, there is an urgent need to identify alternative anticancer agents able to affect new molecular targets. Drimys winteri (Winteraceae) is a medicinal plant, employed in Brazil and many countries, in folk medicine against a variety of ailments, especially for the treatment of fevers, ulcers, pains, affections of respiratory tract and cancers. Previous phytochemical studies have isolated and identified the presence of diverse classes of secondary metabolites in this plant such as sesquiterpenes. In an ongoing to identify new natural anticancer compounds for the treatment and/or prevention of melanoma, we study the effects of Drimys winteri bark ethyl acetate extract and its sesquiterpenes drimenol, nordrimenone, isonordrimenone and polygodial on human melanoma cells. The treatment of melanoma cells with extract, drimenol, isordrimenone and polygodial resulted in a significant reduction in cell viability. But, polygodial showed the highest inhibitory growth activity. In addition, we reported an apoptotic response after treatment with drimenol, isordrimenone and polygodial that probably involves the reduction of Hsp70 expression and reactive oxygen species production. Alternatively, the inhibition of caspase cascade at higher concentrations, correlated with additional reactive oxygen species increase, probably switches natural product-induced cell death from apoptosis to necrosis. Therefore, this evidence provides a scientific support for the anticancer employ of Drimys winteri in traditional medicinal and suggests that active molecules can be considered potential candidates to be tested also in in vivo models, alone or in combination with chemotherapy agents, for the management of melanoma.
黑色素瘤是一种高度侵袭性的癌症，对大多数常规治疗方法具有抗性。因此，迫切需要确定能够影响新的分子靶标的替代抗癌药物。银叶树（Winteraceae）是一种药用植物，在巴西和许多国家用于民间医学，用于治疗各种疾病，特别是发热、溃疡、疼痛、呼吸道疾病和癌症。先前的植物化学研究已经分离并鉴定出这种植物中存在多种类别的次生代谢产物，如倍半萜。为了寻找新的天然抗癌化合物来治疗和/或预防黑色素瘤，我们研究了银叶树树皮乙酸乙酯提取物及其倍半萜 drimenol、nordrimenone、isonordrimenone 和聚戈醛对人黑色素瘤细胞的影响。提取物、drimenol、isordrimenone 和聚戈醛处理黑色素瘤细胞导致细胞活力显著降低。但是，聚戈醛显示出最高的抑制生长活性。此外，我们还报道了在用 drimenol、isordrimenone 和聚戈醛处理后出现的细胞凋亡反应，这可能涉及 Hsp70 表达和活性氧产生的减少。相反，在较高浓度下抑制半胱天冬酶级联反应，与活性氧增加相关，可能会使天然产物诱导的细胞死亡从凋亡转变为坏死。因此，这一证据为银叶树在传统医学中的抗癌应用提供了科学支持，并表明活性分子可以被认为是潜在的候选药物，也可以单独或与化疗药物联合在体内模型中进行测试，用于治疗黑色素瘤。
