In silico identification, high yielding isolation and in vitro validation of 6β-cinnamoyl-7β -hydroxyvouacapen – 5α - ol as a Wnt/β-catenin pathway targeted anti-cancer secondary metabolite of Caesalpinia pulcherrima
Nirwani N. Seneviratne, Tolulope P. Saliu, Fathima T. Muhinudeen, Sanadie D. Gamage, Prabudhi S. Garusinghe, Damith Chathuranga, Vinoda D. Athukorala, Ashein Kothalawala, Asirini H. Jayasekara, Rajitha K. Rathnayaka, Umanda Anjalee De Silva, Mohamed Faries, Thimali H. Weragoda
TL;DR
A compound from the plant Caesalpinia pulcherrima was found to inhibit a key cancer-related pathway and suppress cancer cell growth in multiple cancer types.
Contribution
Identification and validation of 6βCHV as a novel Wnt/β-catenin pathway inhibitor with anti-cancer activity in cancer stem cells.
Findings
6βCHV significantly suppressed proliferation of breast cancer stem cells and other Wnt-dependent cancers with low IC₅₀ values.
6βCHV modulates the Wnt/β-catenin pathway by upregulating p53 and downregulating Cyclin D1 and CD44, inducing apoptosis.
Spectroscopic characterization confirmed the isolated compound as 6βCHV, validating computational predictions.
Abstract
Wnt/β-catenin signaling pathway is frequently dysregulated in cancer stem cells (CSCs), a sub population of cancer cell mass that drives tumor proliferation, metastasis, recurrence, and chemoresistance. Despite its therapeutic significance, no clinically approved drugs specifically target this pathway. In the present study, secondary metabolites of the medicinal plant Caesalpinia pulcherrima was computationally screened by molecular docking, dynamics simulation and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) based free energy calculations to identify potential inhibitors of β-catenin–Tcf/Lef interaction, a key downstream event essential for Wnt/β-catenin signaling. Diterpene metabolite 6β-Cinnamoyl-7β-hydroxyvouacapen-5α-ol (6βCHV) was identified as a potent inhibitor of the pathway along with four previously reported Wnt/β-catenin pathway inhibitors. To validate the…
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Taxonomy
TopicsBiological Stains and Phytochemicals · Wnt/β-catenin signaling in development and cancer · Plant-Derived Bioactive Compounds