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

Abstract

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.

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“…Therefore, we hypothesized that this might be a key pathway involved in the process of PTC metastasis. The PI3K/AKT pathway is a key regulator of cellular processes involved in cell proliferation/the cell cycle, metabolism, apoptosis, and neovascularization [48]. The PI3K/AKT axis could promote tumour metastasis by enhancing cell motility and angiogenesis; for instance, activated AKT could increase the bioactivities of NF-κB and VEGF, which in turn promote enhanced cell motility and angiogenesis.…”

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“…For example, abnormal PI3K-Akt-mTOR signaling is one of the most common dysfunctions present in human cancers (Janku et al 2018). The use of PI3K-Akt as a target in the treatment of cancer has been extensively researched (Hamzehzadeh et al 2018). Phosphatase and tensin homolog (PTEN), a tumor suppressor gene, has been the focus of many studies.…”

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“…Curcumin also exhibits antiangiogenic potential that helps in inhibiting initiation, progression, and metastasis of various cancers such as prostate, colon, and skin cancers (Fadus, Lau, Bikhchandani, & Lynch, ; Li & Cozzi, ). Curcumin inhibits cancer development and progression by targeting the PI3K/AKT signaling pathway in prostate, lung, breast, and ovarian cancers (Yallapu et al, ; Hamzehzadeh, Atkin, Majeed, Butler, & Sahebkar, ; Jin, Qiao, Wang, Xu, & Shang, ; Wang et al, ; Yallapu et al, ; Yu et al, ). Curcumin has also gained much importance in the recent past due to its potential of targeting CSCs (Chan et al, ; Dandawate et al, ; Subramaniam et al, ).…”