A study of how two potential anticancer agents affect major cancer hallmarks: apoptosis and metastasis

Abstract

Cancer is characterized by continuous growth of cells that divide uncontrollably, escaping the standard eliminating mechanism known as apoptosis, which is a form of programmed cell death or suicide. Although abundant efforts have been dedicated to finding an effective cure for cancer, treatment remains a difficult challenge. Many of the current cancer therapies, including chemotherapy, radiation, surgery, immunosuppression, cause many side effects for patients. For that reason, many researchers focus on natural products as they have been used for thousands of years to prevent many chronic diseases, including cancer. Cancer cells are distinguished from healthy cells by certain hallmarks, where each one of those hallmarks requires distinctive capabilities. These hallmarks were defined by Hanahan and Weinberg in 2000, and they include: sustaining proliferating signaling, evading growth suppressors, resisting cell death “apoptosis”, enabling replicative immortality, angiogenesis, activating invasion and metastasis, reprogramming of energy metabolism and evading immune destruction. In this study, we focused on the ability of natural products, either aurones or an oligostilbene, to affect two of the primary cancer hallmarks, inducing apoptosis and inhibiting cancer cell metastasis. Our findings suggest the ability of four aurone derivatives (A3, A5, A10 and A14) based upon five-membered heteroaromatic rings as well as cis- and trans- gnetin H, trimeric resveratrol oligostilbenes, to exhibit the most anticancer activity; growth inhibition was associated with induction of apoptosis as well as repression of cell motility at low concentrations. Together, these findings suggest that aurone derivatives and both cis- and trans- gnetin H could be potential leads for new anti-cancer agents.