Antitumor Effects Of Small Molecule Compound VP394

Cancer is a major disease that harms human health.It is imperative to find effective ways to treat cancer.Chemotherapy is one of the main methods of treating cancer,but with the use of drugs,many cancers show resistance.At present,one of the main methods to overcome drug resistance is to find new drugs for the effective treatment of cancer.Small molecule compounds have been the hotspot of research because of their various advantages,and are the source of new drugs.In this study,the anti-tumor effects of 21 small molecule compounds were studied.It was found that compound VP394 has a significant anti-tumor effect,but it has less toxic side effects on normal cells.By studying the way VP394 induced tumor cell death,it was found that VP394 can induce apoptosis and autophagy in tumor cells.Besides,VP394-induced cell death was rescued after pretreatment with inhibitors of apoptosis and autophagy respectively,indicating apoptosis and autophagy did participate in VP394-induced cell death.At the same time,the study found that VP394 induced tumor cell death accompanied by an increase in ROS levels.When ROS was cleared with ROS scavenger,NAC or Tiron,VP394-induced cell death was rescued and promotion of apoptosis and autophagy was inhibited.Therefore,we believe that ROS is involved in VP394-induced cell death and is involved in the regulation of apoptosis and autophagy.Next,we explored the specific mechanism of VP394-induced tumor cell death.VP394 significantly activated ERK signaling pathway,but did not rescue VP394-induced cell death after inhibiting the activation of ERK signaling pathway,suggesting that VP394 can activate ERK signaling pathway but ERK signaling pathway is not involved in VP394 induced cell death.Next,we found that the expression level of c-Myc can affect the sensitivity of tumor cells to VP394.Cells with high levels of c-Myc expression are more sensitive to VP394,which is associated with c-Myc activating intracellular ROS to promote apoptosis and autophagy.In summary,the small molecule compound VP394 has a good anti-tumor effect,and this discovery will provide new clues and strategies for cancer treatment.