Compound 001 Induces Pyroptosis In Cancer Cells

Cancer is a major problem in the medical community.Chemotherapy is one of the main means of cancer treatment,which causes apoptosis in cancer cells.Traditional chemotherapeutic drugs suppress cancer by causing DNA damage or increasing ROS level.However,there are still many problems with inducing apoptosis to kill cancer cells in chemotherapy.On the one hand,cancer cells enhance metabolic levels and repair DNA damage caused by chemotherapeutic drugs,or new mutations can be occurred through DNA damage and repair,leading cells resistant to apoptosis.On the other hand,traditional chemotherapy drugs have many toxic side effects,such as bone marrow suppression and hair loss.Pyroptosis is a kind of regulated cell death.Recently,researches on the mechanism of pyroptosis have made a breakthrough.In response to the problems of traditional chemotherapeutic drugs,we use HeLa cells as model cells to screen some compounds that can inhibit tumor growth through pyroptosis.We found that compound 001 could induce morphological pattern of pyroptosis in a variety of tumor cells.In the mechanistic study,we demonstrated that in compound 001-induced pyroptosis,GSDMC was cleaved,and caspase family proteins were involved in this process.Knocking down GSDMC effectively abolished pyroptosis induced by compound 001.Other proteins of the gasdermin family were not involved in pyroptosis.Therefore,it is likely that GSDMC is the only executor in the current case.In sum,we indicate that compound 001 can induce pyroptosis in cancer cells,which provides a potential possibility for treating cancer with pyroptosis.It has been reported that GSDMD and GSDME,which are cleaved and activated by caspase,are the executors of pyroptosis.However,we still know less about the biological functions of other members of the gasdermin family,especially in GSDMC.This study not only demonstrates GSDMC-mediated pyroptosis for the first time,but also indicates a novel mechanism of pyroptosis.