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

Abstract

Ethanolic extract of <i>Nelumbo nucifera</i> 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 (<b>1</b>-<b>9</b>). The isolated compounds exhibited potent antiausterity activities. Moreover, under nutrient-deprived conditions, (-)-lirinidine (<b>8</b>) induced remarkable alterations in HeLa cell morphology including cell shrinkage and plasma blebbing leading to total cell death within 10 h. Mechanistically, <b>8</b> 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.