Celastrus paniculatus is a traditional medicinal plant with diverse pharmacological activities. To identify its bioactive constituents, three new β-dihydroagarofuranoid sesquiterpenes were isolated from the whole plant, of which the major constituent is (1α,2α,8β,9β)-1,8-bis(acetyloxy)-2,9-bis(benzoyloxy)-14-hydroxy-β-dihydroagarofuran. It was assessed for its antiproliferative activity, and it suppressed the viability of MCF-7 breast cancer cells with an IC50 of 17±1μM. This growth inhibition was, in part, attributable to apoptosis. Moreover, this drug treatment led to LC3B-II accumulation, indicative of autophagy. Western blot analysis established its ability to target a broad range of signaling effectors related to survival and cell cycle progression, including Akt, NF-κB, p53, and MAP kinases. In addition, flow cytometry analysis indicates increased reactive oxygen species production in response to this compound. Taken together, these findings suggest a pleiotropic mode of mechanism that underlies the antiproliferative activity of this compound in MCF-7 breast cancer cells.
Keywords: 4,6-diamidino-2-phenylindole; Apoptosis; Autophagy; CDK; Celastraceae; Celastrus paniculatus; DAPI; DMSO; ECL; ERK; FBS; LC3B; MAP kinases; PARP; PBS; SDS; Sesquiterpenes; cyclin-dependent kinase; dimethylsulfoxide; enhanced chemiluminescence; extracellular signal-regulated kinases; fetal bovine serum; microtubule-associated protein 1 light chain 3B; mitogen-activated protein kinases; phosphate buffered saline; poly ADP-ribose polymerase; sodium lauryl sulfate.
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