Cristina Ferreira Almeida, Andreia Palmeira, Maria João Valente, Georgina Correia-da-Silva, Anne Marie Vinggaard, Maria Emília Sousa, Natércia Teixeira, Cristina Amaral
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引用次数: 0
Abstract
Background: Breast cancer therapy has been facing remarkable changes. Classic treatments are now combined with other therapies to improve efficacy and surpass resistance. Indeed, the emergence of resistance demands the development of novel therapeutic approaches. Due to key estrogen signaling, estrogen receptor-positive (ER+) breast cancer treatment has always been focused on aromatase inhibition and ER modulation. Lately, the effects of phytocannabinoids, mainly Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have been evaluated in different cancers, including breast. However, Cannabis sativa contains more than 120 phytocannabinoids less researched and understood.
Methods: Here, we evaluated, both in silico and in vitro, the ability of 129 phytocannabinoids to modulate important molecular targets in ER+ breast cancer: aromatase, ER, and androgen receptor (AR).
Results: In silico results suggested that some cannabinoids may inhibit aromatase and act as ERα antagonists. Nine selected cannabinoids showed, in vitro, potential to act either as ER antagonists with inverse agonist properties, or as ER agonists. Moreover, these cannabinoids were considered as weak aromatase inhibitors and AR antagonists with inverse agonist action.
Conclusions: Overall, we present, for the first time, a comprehensive analysis of the actions of the phytocannabinoids in targets of ER+ breast tumors, pointing out their therapeutic potential in cancer and in other diseases.
背景:乳腺癌治疗面临着巨大的变化。传统疗法现在与其他疗法相结合,以提高疗效并克服耐药性。事实上,耐药性的出现要求开发新的治疗方法。由于雌激素信号的关键作用,雌激素受体阳性(ER+)乳腺癌的治疗一直侧重于芳香化酶抑制和ER调节。最近,对植物大麻素(主要是Δ9-四氢大麻酚(THC)和大麻二酚(CBD))在不同癌症(包括乳腺癌)中的作用进行了评估。方法:在此,我们对 129 种植物大麻素调节 ER+ 乳腺癌重要分子靶点(芳香化酶、ER 和雄激素受体(AR))的能力进行了硅学和体外评估:硅学研究结果表明,一些大麻素可能会抑制芳香化酶并充当ERα拮抗剂。九种选定的大麻素在体外显示出作为具有反向激动特性的 ER 拮抗剂或 ER 激动剂的潜力。此外,这些大麻素被认为是弱芳香化酶抑制剂和具有反向激动作用的 AR 拮抗剂:总之,我们首次全面分析了植物大麻素对ER+乳腺肿瘤的作用,指出了它们在癌症和其他疾病中的治疗潜力。