Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16INK4a gene in human colorectal carcinoma (Caco-2) cells

Naselli, Flores; Tesoriere, Luisa; Caradonna, Fabio; Bellavia, Daniele; Attanzio, Alessandro; Gentile, Carla; Livrea, M. A.

doi:10.1016/j.bbrc.2014.06.029

Cited by 62 publications

(56 citation statements)

References 48 publications

(50 reference statements)

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“…When 100 µ M Ind was incubated with CACO2 cells grown for 15 days after confluence, a condition allowing their spontaneous differentiation, no effect was observed on cell viability, indicating an absence of toxicity for nonmalignant cells [24]. …”

Section: Resultsmentioning

confidence: 99%

“…Previously, we proposed the chemopreventive activity of Ind in CACO2 cells in terms of epigenetic modulation of p16 INK4a gene expression [24]. In the present study, anti-proliferative effects and the epigenetic activity of Ind have been investigated in a panel of colorectal cancer cell lines to evaluate the potential of Ind in other transformed cells from the same tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been shown that Ind has an anti-proliferative and pro-apoptotic effect on the human colon cancer cell line CACO2. In the same cells, Ind was able to re-activate the expression of the onco-suppressor p16 INK4a gene, inducing demethylation of its promoter region [24]. …”

Section: Introductionmentioning

confidence: 99%

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Phytochemical Indicaxanthin Inhibits Colon Cancer Cell Growth and Affects the DNA Methylation Status by Influencing Epigenetically Modifying Enzyme Expression and Activity

et al. 2015

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Background: Recently, we have shown anti-proliferative and pro-apoptotic effects of indicaxanthin associated with epigenetic modulation of the onco-suppressor p16^INK4a in the human colon cancer cell line CACO2. In the present study, the epigenetic activity of indicaxanthin and the mechanisms involved were further investigated in other colorectal cancer cell lines. Methods: LOVO1, CACO2, HT29, HCT116, and DLD1 cells were used to evaluate the potential influence of consistent dietary concentrations of indicaxanthin on DNA methylation, and the epigenetic mechanisms involved were researched. Results: Indicaxanthin exhibited anti-proliferative activity in all cell lines but HT29, induced demethylation in the promoters of some methylation-silenced onco-suppressor genes involved in colorectal carcinogenesis (p16^INK4a, GATA4, and ESR1), and left unchanged others which were basally hypermethylated (SFRP1 and HPP1). In apparent contrast, cell exposure to indicaxanthin increased DNMT gene expression, although indicaxanthin appeared to be an inhibitor of DNMT activity. Indicaxanthin also increased the expression of genes involved in DNA demethylation. Finally, an in silico molecular modelling approach suggested stable binding of indicaxanthin at the DNMT1 catalytic site. Conclusions: Our findings contribute to new knowledge in the field of phytochemicals and specifically suggest dietary indicaxanthin as a potential epigenetic agent to protect colon cells against tumoral alterations.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Phytochemical Indicaxanthin Inhibits Colon Cancer Cell Growth and Affects the DNA Methylation Status by Influencing Epigenetically Modifying Enzyme Expression and Activity

et al. 2015

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“…For example, an aqueous extract of Opuntia ficus indica, and its bioactive ingredient, betalain indicaxanthin, reportedly induced demethylation of cyclindependent kinase inhibitor 2A (p16; INK4A; CDKN2A) which is a tumor suppressor gene. 78 Similarly, methylation of the oxidative stress-related gene was modulated by a natural product. For example, Z-ligustilide, isolated from the medicinal herb Radix Angelicae sinensis (RAS), efficiently restored expression of the nuclear factor erythroid 2-like 2 in murine prostate cancer (TRAMP C1) cells.…”

Section: Hdac Inhibitorsmentioning

confidence: 99%

Epigenetic mechanisms in cancer: push and pull between kneaded erasers and fate writers

Farooqı¹,

Tang²,

Li³

et al. 2015

IJN

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Research concerning the epigenome over the years has systematically and sequentially shown substantial development and we have moved from global inhibition of modifications of the epigenome toward identification and targeted therapy against tumor-specific epigenetic mechanisms. In accordance with this approach, several drugs with epigenetically modulating activity have received considerable attention and appreciation, and recently emerging scientific evidence is uncovering details of their mode of action. High-throughput technologies have considerably improved our existing understanding of tumor suppressors, oncogenes, and signaling pathways that are key drivers of cancer. In this review, we summarize the general epigenetic mechanisms in cancer, including: the post-translational modification of DNA methyltransferase and its mediated inactivation of Ras association domain family 1 isoform A, Sonic hedgehog signaling, Wnt signaling, Notch signaling, transforming growth factor signaling, and natural products with epigenetic modification ability. Moreover, we introduce the importance of nanomedicine for delivery of natural products with modulating ability to epigenetic machinery in cancer cells. Such in-depth and comprehensive knowledge regarding epigenetic dysregulation will be helpful in the upcoming era of molecular genomic pathology for both detection and treatment of cancer. Epigenetic information will also be helpful when nanotherapy is used for epigenetic modification.

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“…The authors reported that the concentration of the aqueous extract from cactus pear fruits (1%) is effective in 40-60% inhibition of growth of cervical cancer cells and immortalized cervical epithelium; and the inhibition of growth may get close to 100%, depending on the cancer cell, the dose and time of exposure to the extracts. Naselli et al (2014) ), when incubated for 48 hours. These studies corroborate the results presented in this study, and enhance the cytotoxic activity of cactus pear extracts against some cells of human cancer, where this activity depends on the concentration and time of exposure to the extract.…”

Section: Determination Of Cytotoxic Activitymentioning

confidence: 99%

Genetic diversity and seasonal chemical profile by 1H NMR and cytotoxic activity in Opuntia and Nopalea genres

Francisco¹,

Albericio²,

Riselane³

et al. 2016

J. Med. Plants Res.

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The cactus pear (Opuntia spp.) is known to have bioactive compounds which work in the prevention of various diseases, especially cancer. The objectives of the study were to characterize the chemical profile and genetic diversity, through chromatic tests and ) shows limited growth inhibitory effect on the cancer cell lines examined. It is concluded that the cytotoxic activity of cactus pear cladodes is attributed to phenolic compounds especially the flavonoids. It is recommended that population at risk utilize these materials as preventative natural dietary supplements against cancer.

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Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16INK4a gene in human colorectal carcinoma (Caco-2) cells

Cited by 62 publications

References 48 publications

Phytochemical Indicaxanthin Inhibits Colon Cancer Cell Growth and Affects the DNA Methylation Status by Influencing Epigenetically Modifying Enzyme Expression and Activity

Phytochemical Indicaxanthin Inhibits Colon Cancer Cell Growth and Affects the DNA Methylation Status by Influencing Epigenetically Modifying Enzyme Expression and Activity

Epigenetic mechanisms in cancer: push and pull between kneaded erasers and fate writers

Genetic diversity and seasonal chemical profile by 1H NMR and cytotoxic activity in Opuntia and Nopalea genres

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