Department of Inorganic and Organic Chemistry and Biochemistry, Faculty of Chemical and Technological Sciences, School of Medicine of Ciudad Real, Regional Center of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), Ciudad Real, Spain.
Front Endocrinol (Lausanne). 2022 Nov 3;13:1007801. doi: 10.3389/fendo.2022.1007801. eCollection 2022.
Despite great efforts, effective treatment against cancer has not yet been found. However, natural compounds such as the polyphenol resveratrol have emerged as promising preventive agent in cancer therapy. The mode of action of resveratrol is still poorly understood, but it can modulate many signaling pathways related to the initiation and progression of cancer. Adenosinergic signaling may be involved in the antitumoral action of resveratrol since resveratrol binds to the orthosteric binding site of adenosine A receptors and acts as a non-selective agonist for adenosine receptors. In the present study, we measured the impact of resveratrol treatment on different adenosinergic pathway components (i.e. adenosine receptors levels, 5'-nucleotidase, adenosine deaminase, and adenylyl cyclase activities, protein kinase A levels, intracellular adenosine and other related metabolites levels) and cell viability and proliferation in HeLa and SH-SY5Y cell lines. Results revealed changes leading to turning off cAMP signaling such as decreased levels of A receptors and reduced adenylyl cyclase activation, increased levels of A receptors and increased adenylyl cyclase inhibition, and lower levels of PKA. All these changes could contribute to the antitumoral action of resveratrol. Interestingly, these effects were almost identical in HeLa and SH-SY5Y cells suggesting that resveratrol enhances A and hinders A adenosine receptors signaling as part of a potential mechanism of antitumoral action.
尽管付出了巨大努力，但仍未找到有效的癌症治疗方法。然而，多酚白藜芦醇等天然化合物已成为癌症治疗中很有前途的预防剂。白藜芦醇的作用机制仍知之甚少，但它可以调节与癌症发生和进展相关的许多信号通路。腺苷能信号可能参与白藜芦醇的抗肿瘤作用，因为白藜芦醇结合到腺苷 A 受体的正位结合位点，并作为腺苷受体的非选择性激动剂。在本研究中，我们测量了白藜芦醇处理对不同腺苷能途径成分（即腺苷受体水平、5'-核苷酸酶、腺苷脱氨酶和腺苷酸环化酶活性、蛋白激酶 A 水平、细胞内腺苷和其他相关代谢物水平）以及 HeLa 和 SH-SY5Y 细胞系的细胞活力和增殖的影响。结果显示，导致 cAMP 信号关闭的变化，如 A 受体水平降低和腺苷酸环化酶激活减少、A 受体水平升高和腺苷酸环化酶抑制增加以及蛋白激酶 A 水平降低。所有这些变化都可能有助于白藜芦醇的抗肿瘤作用。有趣的是，这些效应在 HeLa 和 SH-SY5Y 细胞中几乎相同，表明白藜芦醇增强 A 并抑制 A 腺苷受体信号，作为抗肿瘤作用的潜在机制的一部分。
