Caffeic Acid targets metabolism of cervical squamous cell carcinoma

Abstract

Abstract Caffeic Acid (trans-3,4-dihydroxycinnamic acid) is a representative of hydroxycinnamic acids that selectively modulates reprogrammed metabolism in cervical cancer cells. In particular, Caffeic Acid causes a shift in mitochondrial metabolism toward the tricarboxylic acid cycle (TCA cycle, Krebs cycle), which results in oxidative stress and activation of apoptosis in epithelial cervical tumor cells. Furthermore, Caffeic Acid hinders NADPH regeneration by Malic Enzyme 1 (ME1) inhibition and that way it additionally impairs the cellular defense against oxidative stress in tumor cells. Caffeic Acid controls the expression of proteins that regulate the glycolytic phenotype of tumor cells. The multiple activities of Caffeic Acid on cellular metabolism lead to energetic stress and activation of adenosine 5′-monophosphate AMP-activated protein kinase (AMPK). The action of Caffeic Acid on metabolic processes selectively kills cancer but not normal cells. Currently, intensive ongoing studies focus on identification of molecular targets in regulation of metabolism of tumor cells. A lot of effort has been put into establishing combinatory therapies to improve efficacy and minimalize toxicity of anticancer treatments. Caffeic Acid, together with the antidiabetic drug, Metformin, sensitizes cervical cancer cells with metastatic phenotype to cytotoxic action of Cisplatin and supports selective elimination of tumor cells. Therefore, Caffeic Acid may be considered to be a potential adjuvant in future therapeutic strategies for cervical cancer.