Benzylisoquinoline alkaloids from Nelumbo nucifera Gaertn. petals with antiausterity activities against the HeLa human cervical cancer cell line.

Ethanolic extract of Nelumbo nucifera petals showed preferential cytotoxic activity against HeLa human cervical cancer cell line with a PC50 value of 10.4 μg/mL. This active extract was subjected to a phytochemical investigation study which led to the isolation of nine benzylisoquinoline alkaloids (1-9). The isolated compounds exhibited potent antiausterity activities. Moreover, under nutrient-deprived conditions, (-)-lirinidine (8) induced remarkable alterations in HeLa cell morphology including cell shrinkage and plasma blebbing leading to total cell death within 10 h. Mechanistically, 8 was found to inhibit Akt/mTOR signaling pathway. It also induced apoptosis by promoting caspase-3 activation and inhibiting Bcl-2 expression. Therefore, benzylisoquinoline alkaloids skeleton can be considered as a promising scaffold for the anticancer drug development against cervical cancer.