An increasing amount of evidence suggests that transmembrane member 16A (TMEM16A)-encoded Ca²⁺-activated Cl⁻ channels play a crucial role in regulating tumorigenesis. Therefore, specific and potent TMEM16A inhibitors have been proposed to potentially be useful for the treatment of cancer. During drug screening, we found that benzophenanthridine alkaloids (sanguinarine, sanguinarium chloride, sanguinarine nitrate, ethoxysanguinarine, chelerythrine, and dihydrosanguinarine) potently inhibited the recombinant TMEM16A current. The IC₅₀ and E_max values for TMEM16A inhibition of six tested benzophenanthridine alkaloids were 5.6–12.3 μM and 77–91%, respectively. These benzophenanthridine alkaloids also significantly inhibited the endogenous TMEM16A currents and proliferation, migration, and induced apoptosis in LA795 lung adenocarcinoma cells. These data demonstrate that benzophenanthridine alkaloids are novel TMEM16A inhibitors and are potentially useful in specific cancer therapies. These findings also provide new insight for the development of TMEM16A inhibitors.

越来越证据量表明，跨膜部件16A（TMEM16A）编码的Ca ²⁺激活的氯^-通道在调节发生过程中起了至关重要的作用。因此，已经提出了特异性和有效的TMEM16A抑制剂潜在地可用于治疗癌症。在药物筛选过程中，我们发现苯甲菲啶生物碱（血红蛋白，血红蛋白，硝酸血红蛋白，乙氧基血红蛋白，白屈菜红碱和二氢血红蛋白碱）有效抑制重组TMEM16A电流。IC ₅₀和E _maxTMEM16A抑制6种被测苯并菲啶生物碱的值分别为5.6-12.3μM和77-91％。这些苯并菲啶生物碱还显着抑制内源性TMEM16A电流以及LA795肺腺癌细胞的增殖，迁移和诱导凋亡。这些数据表明，苯并菲啶生物碱是新型的TMEM16A抑制剂，可能在特定的癌症治疗中有用。这些发现也为TMEM16A抑制剂的开发提供了新的见识。