Indole-3-carbinol induces tumor cell death: function follows form

Megna, Bryant; Carney, Patrick R.; Nukaya, Manabu; Geiger, Peter; Kennedy, Gregory D.

doi:10.1016/j.jss.2016.04.021

Cited by 80 publications

(44 citation statements)

References 44 publications

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“…Taken together, we assume that the LS513 cells contain not only an enhanced battery of MDR pumps (translating to their relative resistance illustrated in the cell viability figure), but also a larger expression pool of drug metabolizing enzymes, namely the CYP family. The phenomenon of the LS513 line exhibiting comparatively robust AHR activation was also apparent in a previous publication of ours utilizing a natural ligand of the AHR, indole-3-carbinol (47). …”

Section: Discussionsupporting

confidence: 75%

The aryl hydrocarbon receptor as an antitumor target of synthetic curcuminoids in colorectal cancer

Megna

Carney

Depke

et al. 2017

Journal of Surgical Research

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BACKGROUND Curcumin has proven to be a potent antitumor agent in both preclinical and clinical models of colorectal cancer (CRC). It has also been identified as a ligand of the transcription factor known as the aryl hydrocarbon receptor (AHR). Our lab has identified the AHR as a mechanism which contributes to both tumorigenesis in a mouse model of inflammatory CRC as well an apoptotic target in vitro. Curcumin’s role as an AHR ligand may modulate its effects to induce colon cancer cell death, and this role may be enhanced via structural modification of the curcumin backbone. We sought to determine if the two piperidone analogs of curcumin, RL66 and RL118, exhibit more robust antitumor actions than their parent compound in the context of colorectal cancer in vitro. Moreover, to ascertain the ability of curcumin, RL66, and RL118 to activate the aryl hydrocarbon receptor and evaluate if this activation has any effect on CRC cell death. MATERIALS AND METHODS DLD1, HCT116, LS513, and RKO colon cell lines were propagated in vitro. Natural curcumin was obtained commercially, while RL66 and RL118 were synthesized and characterized de novo. Multi-well fluorescent/luminescent signal detection was utilized to simultaneously ascertain cell viability, cell cytonecrosis, and relative amounts of apoptotic activity. AHR activity was measured with a dual luciferase reporter gene system. Stable expression of siRNA interference was established in the HCT116 cell lines to create AHR “knock down” cell lines. RESULTS Both RL66 and RL118 proved to be more potent antitumor agents than their parent compound curcumin in all cell lines tested. The majority of this cell death was due to induction of apoptosis, which occurred earlier and to a greater degree following RL66 and RL118 treatment as opposed to curcumin. Also, RL66 and RL118 were found to be activators of AHR, and a portion of their ability to cause cell death was dependent on this induction. Curcumin was found unable to activate the AHR, and levels of AHR mRNA did not change its effects on cell death. CONCLUSION Piperidone analogs of curcumin exhibited enhanced antitumor effects in vitro as opposed to their parent compound. Even more, this enhanced cell death profile may be partially attributed to the ability of these compounds to activate the AHR. Further study of synthetic curcumin analogs as chemopreventives and chemoadjuncts in CRC is warranted. Also, more generally, the AHR may represent a potential putative target for novel anticancer agents for CRC.

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Section: Discussionsupporting

confidence: 75%

The aryl hydrocarbon receptor as an antitumor target of synthetic curcuminoids in colorectal cancer

Megna

Carney

Depke

et al. 2017

Journal of Surgical Research

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“…A number of natural compounds have been found to inhibit one or more pathways that contribute to proliferation of cancer cells and metastatic processes [ 4 ]. The most investigated and promising compounds studied in the last years include: curcumin [ 5 ], resveratrol [ 6 ], and indole-3-carbinol [ 7 ], which are naturally present in some species of fruit and vegetables.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Adjuvant Fermented Wheat Germ Extract on Cancer Cell Lines: A Systematic Review

et al. 2018

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Fermented wheat germ extract (FWGE; trade name AVEMAR) is a natural compound derived from industrial fermentation of wheat germ. Its potential anticancer properties has emerged from recent studies. The aim of this systematic review is to summarize the data available in the scientific literature concerning the in vitro activity of FWGE on malignant cells. A systematic review of English articles in electronic databases has been performed. The primary outcomes of the review regarded types of cancer cell lines subjected to the investigation and the main results concerning cell viability, proliferation, and apoptosis observed within the studies. Sixteen articles were included in the final qualitative analysis. Various types of cancer cells treated with FWGE have been analyzed, showing mainly cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis. FWGE can be a promising drug component in cancer treatment; however, further in vitro and in vivo studies are necessary to prove its effectiveness and safety in humans.

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“…This cell line has not been infected or transfected with any genetic information, and is widely used because there are few other noncancerous colon cell lines [ 21 ]. Although there are several cancerous colon cell lines (e.g., HCT116, HT29, and Caco-2) available, most of these cell lines are derived from adenocarcinoma, and only the HCT116 cell line is derived from carcinoma [ 22 , 23 ]. It is known that adenocarcinoma develops in glands whereas carcinoma originates in the epithelial tissue, and there are differences between colorectal carcinoma and advanced adenomas [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells

et al. 2017

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Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Butyrate inhibited cell proliferation, and led to an induction of apoptosis, genomic DNA fragmentation in HCT116 cells, but to a lesser extent in NCM460 cells. Although butyrate increased H3 histone deacetylation and p21 tumor suppressor expression in both cell types, p21 protein level was greater with intense expression around the nuclei in HCT116 cells when compared with that in NCM460 cells. Furthermore, butyrate treatment increased the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2), a survival signal, in NCM460 cells while it decreased p-ERK1/2 in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic potential in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.

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Indole-3-carbinol induces tumor cell death: function follows form

Cited by 80 publications

References 44 publications

The aryl hydrocarbon receptor as an antitumor target of synthetic curcuminoids in colorectal cancer

The aryl hydrocarbon receptor as an antitumor target of synthetic curcuminoids in colorectal cancer

The Effects of Adjuvant Fermented Wheat Germ Extract on Cancer Cell Lines: A Systematic Review

Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells

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