Potential Mechanisms of Action of Curcumin for Cancer Prevention: Focus on Cellular Signaling Pathways and miRNAs

Abstract

Despite significant progressions in treatment modalities over the last decade, either cancer incidence or mortality is continuously on the rise throughout the world. Current anticancer agents display limited efficacy, accompanied by severe side effects. In order to improve therapeutic outcomes in patients with cancer, it is crucial to identify novel, highly efficacious pharmacological agents. Curcumin, a hydrophobic polyphenol extracted from turmeric, has gained increasing attention due to its powerful anticancer properties. Curcumin can inhibit the growth, invasion and metastasis of various cancers. The anticancer mechanisms of curcumin have been extensively studied. The anticancer effects of curcumin are mainly mediated through its regulation of multiple cellular signaling pathways, including Wnt/β-catenin, PI3K/Akt, JAK/STAT, MAPK, p53 and NF-ĸB signaling pathways. Moreover, curcumin also orchestrates the expression and activity of oncogenic and tumor-suppressive miRNAs. In this review, we summarized the regulation of these signaling pathways by curcumin in different cancers. We also discussed the modulatory function of curcumin in the downregulation of oncogenic miRNAs and the upregulation of tumor-suppressive miRNAs. An in-depth understanding of the anticancer mechanisms of curcumin will be helpful for developing this promising compound as a therapeutic agent in clinical management of cancer.

Evidence That Calebin A, a Component of Curcuma Longa Suppresses NF-κB Mediated Proliferation, Invasion and Metastasis of Human Colorectal Cancer Induced by TNF-β (Lymphotoxin)

“…Interestingly, it has been previously shown that TNF-β-induced CRC proliferation can be suppressed by other natural substances such as resveratrol and curcumin [13]. Indeed, curcumin has been shown to inhibit tumor cell proliferation, migration and metastasis in multiple tumors [49,50]. Thereby, it modulates a large range of intracellular signalling pathways, including PI3K/Akt, Wnt/β-catenin, JAK/STAT, p53 and NF-κB pathway [19,49].…”

Neuroprotective effects of curcumin through autophagy modulation

“…As a medical herb, C. longa exhibits antioxidant, anti‐inflammatory, anti‐tumor and chemosensitizing, hepatoprotective, lipid‐modifying, and neuroprotective effects, and is suggested to improve mental illnesses . Curcumin (1,7‐bis[4‐hydroxy‐3‐methoxyphenyl]‐1,6‐heptadiene‐3,5‐dione) is scientifically known as diferuloylmethane, derived from the rhizomes of C. longa . Curcumin is the main active component in turmeric which constitutes for approximately 2–5% of turmeric .…”

“…Curcumin (1,7‐bis[4‐hydroxy‐3‐methoxyphenyl]‐1,6‐heptadiene‐3,5‐dione) is scientifically known as diferuloylmethane, derived from the rhizomes of C. longa . Curcumin is the main active component in turmeric which constitutes for approximately 2–5% of turmeric . Curcumin contains three main compounds—80% curcuminoid complex, 17% dimethoxy‐curcumin, and 3% bisdemethoxy‐curcumin .…”

“…46 Curcumin is the main active component in turmeric which constitutes for approximately 2-5% of turmeric. 46,47 Curcumin contains three main compounds-80% curcuminoid complex, 17% dimethoxycurcumin, and 3% bisdemethoxy-curcumin. 48,49 Research has demonstrated that curcumin possess health benefits due to its antioxidant, 50 anti-inflammatory, 51 antibacterial, antiviral, antifungal activity, 52 and anti-tumor 53,54 effects.…”

“…90 Increasing data suggests that autophagy participates in the pathological process of cerebral ischemia. 91 Wang et al (2019) reported that curcumin decreased the expression of LC3-II and hypoxiainducible factors (HIF)-1α, while increasing P62 levels, leading to reduced death and apoptosis in an in vitro model of ischemic-reperfusion injury. 69 Cerebral ischemic-reperfusion injury resulted in significant alterations in the expression of LC3-II/LC3-I, IL-1, TLR4, and p-p38 which was attenuated by curcumin treatment.…”