The versatile role of curcumin in cancer prevention and treatment: A focus on PI3K/AKT pathway

Despite significant advances in treatment modalities, millions of cancer-related deaths continue to occur annually, often as a consequence of developing resistance against the range of available chemotherapeutic drugs. Furthermore, available anti-cancer chemotherapeutic agents show limited efficacy, often have severe side effects, and are expensive. Thus, the discovery of pharmacological agents that do not have these disadvantages is necessary. Curcumin, a polyphenolic compound derived from turmeric (Curcumin longa L.), is one such agent that has been widely studied for its anti-inflammatory and/or anti-cancer effects. Curcumin exerts its anti-cancer effect by suppressing the initiation, progression, and metastasis of a variety of cancers and appears to inhibit carcinogenesis by affecting two main processes: angiogenesis and tumor growth. These anti-cancer effects are largely mediated via negative regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other oncogenic molecules. The PI3K/AKT pathway is commonly activated in cancer initiation and progression. Considered to be the key signaling pathway, the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway therefore represents a key target for cancer therapeutics. In the current review, we focus upon curcumin's targeting of PI3K/AKT in different malignancies to effect inhibition of cancer development and progression.