Exploration of Phaeanthine: A Bisbenzylisoquinoline Alkaloid Induces Anticancer Effect in Cervical Cancer Cells Involving Mitochondria-Mediated Apoptosis.
Alisha ValsanMurugan Thulasi MeenuVishnu Priya MuraliBeutline MalgijaAnuja Gracy JosephPrakasan NishaKokkuvayil Vasu RadhakrishnanKaustabh Kumar MaitiPublished in: ACS omega (2023)
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.
Keyphrases
- molecular docking
- cell cycle arrest
- cell death
- signaling pathway
- molecular dynamics simulations
- pi k akt
- cell proliferation
- induced apoptosis
- oxidative stress
- binding protein
- protein protein
- healthcare
- reactive oxygen species
- molecular dynamics
- emergency department
- anti inflammatory
- endoplasmic reticulum stress
- oxide nanoparticles
- clinical evaluation
- adverse drug
- case control
- small molecule