Exploration of Phaeanthine: A Bisbenzylisoquinoline Alkaloid Induces Anticancer Effect in Cervical Cancer Cells Involving Mitochondria-Mediated Apoptosis

[Image: see text] Natural-product-based pharmacophores possess considerably more structural diversity, attractive physicochemical features, and relatively less toxicity than synthesized drug entities. In this context, our studies on phaeanthine, a bisbenzylisoquinoline alkaloid isolated from the rhizomes of Cyclea peltata (Lam) Hook.f & Thoms., showed selective cytotoxicity toward cervical cancer cells (HeLa) with an IC(50) of 8.11 ± 0.04 μM. Subsequent investigation with in silico molecular docking of phaeanthine displayed preferential binding to the antiapoptotic protein Akt as reflected by a docking score of −5.023. Interestingly, the follow-up in vitro assessment of the compound correlated with mitochondria-mediated apoptosis specifically by downregulating the expression of Akt and p-Akt, including other antiapoptotic proteins MCl-1, IGF-2, and XIAP. In the complementary in vitro assessment, mitochondrial membrane polarization and dynamics of intercellular cytochrome c validated the intrinsic mechanism of the apoptotic phenomenon. To the best of our knowledge, this is the first comprehensive anticancer profiling study of phaeanthine against HeLa cells.