Carnosic acid increases sorafenib-induced inhibition of ERK1/2 and STAT3 signaling which contributes to reduced cell proliferation and survival of hepatocellular carcinoma cells.

Carnosic acid increases sorafenib-induced inhibition of ERK1/2 and STAT3 signaling which contributes to reduced cell proliferation and survival of hepatocellular carcinoma cells. Oncotarget. 2020 Aug 18;11(33):3129-3143 Authors: Wang X, Gupta P, Jramne Y, Danilenko M, Liu D, Studzinski GP Abstract Hepatocellular carcinoma (HCC) has increasing worldwide incidence but when unresectable lacks curative options. Treatment with a kinase inhibitor Sorafenib (Sf), while initially effective, results in only short increases in patient survival, thus there is a need for improved treatment regimens. Numerous treatment regimens have been explored wherein Sf is combined with other agents, such as non-toxic botanicals like Curcumin or Silibinin. Recently, we have shown that carnosic acid (CA), a component of the food preservative Rosemary Extract, can markedly enhance the cytotoxic actions of Sf in several cell lines derived from HCC, but not in the cell line Hu1545 derived from normal hepatocytes. CA has been shown to enhance Sf-induced cell death in the neoplastic cell lines, principally due to the composite of increased apoptosis and cytotoxic autophagy. In the present study we focused on the mechanisms that underlie the reduced proliferation and survival of HCC cells when CA is added to Sf and how this relates to the increase in Sf-induced DNA damage as well as to the elevation of cytoplasmic levels of reactive oxygen species (ROS). Importantly...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research