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Therapeutic Applications of Curcumin and Derivatives in Colorectal Cancer.

ABSTRACT: Curcumin (CUR), a natural phenolic compound, has been increasingly investigated in several malignancies due to its safe profile and ability to affect a wide range of oncogenic targets. With the ability to affect metastasis, apoptosis, and angiogenesis in colorectal cancer (CRC) and its tolerability at high doses, CUR is an attractive target for study. However, poor bioavailability and unfavorable pharmacokinetics and pharmacodynamics have hampered CUR's efficacy in clinical trials. Development of its derivatives and alternative delivery methods have shown the potential to overcome its inherent bioavailability issues. Recent analyses of various derivatives and nanoparticle encapsulation of CUR have demonstrated increased effectiveness in CRC studies. A major advantage of CUR has been its synergistic effects when used in combination with various chemotherapeutic agents. CUR offers a unique treatment option in terms of patient safety and its ability to be used in combination with current treatments for CRC. Further development of its derivatives and alternative delivery options offer potential new avenues of treatment that could outperform previous efforts to establish CUR as a CRC therapy.

SUBMITTER: Lambring C

PROVIDER: S-EPMC10262216 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Therapeutic Applications of Curcumin and Derivatives in Colorectal Cancer.

Lambring Christoffer C Varga Kelly K Livingston Keriman K Lorusso Nicholas N Dudhia Amil A Basha Riyaz R

Onco therapeutics 20220101 1

Curcumin (CUR), a natural phenolic compound, has been increasingly investigated in several malignancies due to its safe profile and ability to affect a wide range of oncogenic targets. With the ability to affect metastasis, apoptosis, and angiogenesis in colorectal cancer (CRC) and its tolerability at high doses, CUR is an attractive target for study. However, poor bioavailability and unfavorable pharmacokinetics and pharmacodynamics have hampered CUR's efficacy in clinical trials. Development o ...[more]

PMID: 37324055

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Project description:AimRecent evidence suggests that several dietary polyphenols may exert their chemopreventive effect through epigenetic modifications. Curcumin is one of the most widely studied dietary chemopreventive agents for colon cancer prevention, however, its effects on epigenetic alterations, particularly DNA methylation, remain unclear. Using systematic genome-wide approaches, we aimed to elucidate the effect of curcumin on DNA methylation alterations in colorectal cancer cells.Materials and methodsTo evaluate the effect of curcumin on DNA methylation, three CRC cell lines, HCT116, HT29 and RKO, were treated with curcumin. 5-aza-2'-deoxycytidine (5-aza-CdR) and trichostatin A treated cells were used as positive and negative controls for DNA methylation changes, respectively. Methylation status of LINE-1 repeat elements, DNA promoter methylation microarrays and gene expression arrays were used to assess global methylation and gene expression changes. Validation was performed using independent microarrays, quantitative bisulfite pyrosequencing, and qPCR.ResultsAs expected, genome-wide methylation microarrays revealed significant DNA hypomethylation in 5-aza-CdR-treated cells (mean ?-values of 0.12), however, non-significant changes in mean ?-values were observed in curcumin-treated cells. In comparison to mock-treated cells, curcumin-induced DNA methylation alterations occurred in a time-dependent manner. In contrast to the generalized, non-specific global hypomethylation observed with 5-aza-CdR, curcumin treatment resulted in methylation changes at selected, partially-methylated loci, instead of fully-methylated CpG sites. DNA methylation alterations were supported by corresponding changes in gene expression at both up- and down-regulated genes in various CRC cell lines.ConclusionsOur data provide previously unrecognized evidence for curcumin-mediated DNA methylation alterations as a potential mechanism of colon cancer chemoprevention. In contrast to non-specific global hypomethylation induced by 5-aza-CdR, curcumin-induced methylation changes occurred only in a subset of partially-methylated genes, which provides additional mechanistic insights into the potent chemopreventive effect of this dietary nutraceutical.

Dataset Information

Therapeutic Applications of Curcumin and Derivatives in Colorectal Cancer.

Publications

Therapeutic Applications of Curcumin and Derivatives in Colorectal Cancer.

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