The Mechanisms Of Bound Polyphenol Of Inner Shell Inducing Autophagic Death Of Breast Cancer Cells

Breast cancer is the most common cancer in women,which is often accompanied by serious side effects during the treatment process.Therefore,it is urgent to find an effective and non-toxic drug.Our previous researches have found that there are abundant polyphenols in grain bran.Especially Bound polyphenol of inner shell(BPIS)has strong anti-inflammatory,anti-oxidant ability and broad-spectrum anticancer effects.However,the molecular mechanism of BPIS to inhibit breast cancer cells is still unclear.Therefore,in order to clarify the mechanism of BPIS inhibiting breast cancer,we will explore the following aspects:1.Cell cloning assay,PI staining assay and Trypan blue staining assay showed that breast cancer cells MCF-7 and MDA-MB-231 were significantly inhibited,after BPIS treatment.However,mammary epithelial cells MCF-10 A were not sensitive to BPIS.These results showed that BPIS can specifically inhibit breast cancer cells.Furthermore,we found that autophagy played an important role in it through network pharmacology.2.We found that the autophagy level was significantly increased after BPIS treatment by using the western blot,plasmid transfection and transmission electron microscopy.After 3-MA and CQ were used to pretreat breast cancer cells,the inhibitory effect of BPIS on breast cancer cells was not significantly,indicating that BPIS inhibited breast cancer cells through autophagy.3.Through the detection of lipid content in breast cancer cells,we found that lipids were significantly accumulated in breast cancer cells,after BPIS treatment.UPLC/MS lipidomics was used to analyze the lipids in breast cancer cells,and found that BPIS activated sphingolipid metabolism pathway and glycerophospholipid metabolism pathway.4.The rate-limiting enzyme of sphingolipid metabolism pathway and glycerophospholipid metabolism pathway in breast cancer cells was detected.It was found that BPIS promoted the accumulation of lipids and autophagy in breast cancer cells by induced the expression of the PCYT1 A,which leaded to autophagic cell death.