Cinobufotalin as a Novel Agent to Inhibit in Vitro Epithelial Ovarian Cancer Cell Proliferation, Migration and Invasion
2016
Objective: Cinobufotalin (CINO), a cardiotonic steroid (CTS) or
bufadienolide, is extracted from the skin secretions of giant toads and is
utilized in traditional Chinese medicine (Chan Su). CINO has been used as a
cardiotonic, diuretic and a hemostatic agent. Recently, CINO has been shown to
inhibit lung cancer cell function and has been implicated in several other
disease processes. In this study, we pursued the potential anticancer
application of CINO using the ovarian tumor cell line SK-OV-3. Study Design: We
evaluated the effect of CINO on cultures of SK-OV-3. Cells were treated with
0.1, 0.5, 1, 5, and 10 μM CINO. Cell proliferation, migration, invasion, and
viability were measured using commercially available kits. Cell cycle
progression was evaluated by a Cell Cycle Phase Determination Kit. Apoptosis
was evaluated by an Apoptotic Blebs Assay Kit; cell cycle arrest and apoptotic
signaling were determined by fluorescence-activated cell sorting (FACS)
analysis. Results: CINO at ≥ 0.5 μM inhibited SKOV-3 cell proliferation,
migration, and invasion (p < 0.05). There was a higher (p < 0.05)
percentage of S phase cells in groups treated with CINO at 0.5 μM. CINO at ≥
0.5 μM down regulated expression of Proliferating Cell Nuclear Antigen (PCNA)
and caused cell death. Conclusion: This data demonstrates that CINO impairs
SK-OV-3 cell function via cell cycle arrest and apoptotic signaling, suggesting
CINO be further investigated as a novel anti-ovarian cancer agent.
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