dihydroagarofuran and Breast-Neoplasms

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.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Autophagy; Blotting, Western; Breast Neoplasms; Celastrus; Cell Proliferation; Cell Survival; Female; Flow Cytometry; Humans; Inhibitory Concentration 50; MCF-7 Cells; Microtubule-Associated Proteins; Mitogen-Activated Protein Kinases; Molecular Structure; NF-kappa B; Plant Extracts; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Sesquiterpenes; Tumor Suppressor Protein p53