Jiang Weiyu, Dai Zhao, Chen Guangping
Department of Physiological Sciences, Center for Veterinary Health Sciences, USA.
School of Environmental and Chemical Engineering, China.
Biomed J Sci Tech Res. 2019;22(5):16960-16967. doi: 10.26717/bjstr.2019.22.003812. Epub 2019 Nov 13.
Estrogens are known for their proliferative effects, resulting in tumorigenesis and causing cancers. The majority of breast cancers are estrogen-dependent. Estrogenb-locking drugs developed for treating estrogen-dependent breast cancers include antagonists of estrogen receptors (ERs) and inhibitors of estrogen synthesis enzymes such as aromatase and steroid sulfatase (STS). However, drugs targeting estrogen inactivation enzyme, estrogen sulfotransferase (SULT1E1), have not been developed for estrogen-dependent cancer treatment or prevention. Estrogens must be inactivated after their actions by SULT1E1, uncontrolled estrogen activity in certain tissues will cause cancers. The majority of human breast cancer cell lines are known to express very low levels of SULT1E1 compared to normal mammary cells. Therefore, gene up-regulation of SULT1E1 could provide novel possibilities for the treatment of estrogen-dependent breast and endometrial cancers. Our data suggest that certain nutritional flavonoids induce SULT1E1 and inhibit cell proliferation in estrogen-dependent breast cancer MCF-7 cells. Our results also suggest that SULT1E1 inducer has an additive or synergistic effect on the inhibition of MCF-7 cell proliferation when combined with other known breast cancer drugs. Naturally occurring flavonoids are safe and inexpensive; they could be used for the prevention of certain breast cancers and/or used as co-drug for the treatment of estrogen-dependent cancers. These results may lead to creating innovative approaches for the treatment or prevention of estrogen-dependent cancers and may lead to the discovery of novel drugs or co-drugs.
雌激素因其增殖作用而闻名，可导致肿瘤发生并引发癌症。大多数乳腺癌依赖雌激素。为治疗依赖雌激素的乳腺癌而研发的雌激素阻断药物包括雌激素受体（ERs）拮抗剂以及芳香化酶和类固醇硫酸酯酶（STS）等雌激素合成酶抑制剂。然而，针对雌激素失活酶——雌激素硫酸转移酶（SULT1E1）的药物尚未被开发用于依赖雌激素的癌症治疗或预防。雌激素在发挥作用后必须被SULT1E1失活，否则某些组织中不受控制的雌激素活性会引发癌症。与正常乳腺细胞相比，大多数人乳腺癌细胞系已知表达极低水平的SULT1E1。因此，SULT1E1的基因上调可为依赖雌激素的乳腺癌和子宫内膜癌的治疗提供新的可能性。我们的数据表明，某些营养类黄酮可诱导SULT1E1并抑制依赖雌激素的乳腺癌MCF - 7细胞的增殖。我们的结果还表明，SULT1E1诱导剂与其他已知乳腺癌药物联合使用时，对抑制MCF - 7细胞增殖具有相加或协同作用。天然存在的类黄酮安全且廉价；它们可用于预防某些乳腺癌和/或用作治疗依赖雌激素癌症的辅助药物。这些结果可能会带来治疗或预防依赖雌激素癌症的创新方法，并可能导致发现新型药物或辅助药物。
