Epigenetic reactivation of p21CIP1/WAF1 and KLOTHO by a combination of bioactive dietary supplements is partially ERα-dependent in ERα-negative human breast cancer cells

Sinha, Sonam; Shukla, Samriddhi; Khan, Sajid; Tollefsbol, Trygve O.; Meeran, Syed Musthapa

doi:10.1016/j.mce.2015.02.020

Cited by 42 publications

(23 citation statements)

References 48 publications

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“…The CDKN1A encodes p21 CIP1/WAF1 protein, a cyclin‐dependent kinase inhibitor (CDKI), which acts as a tumor suppressor and induces G1 or G2/M cell cycle accumulation, proliferation inhibition, and apoptosis . Expression of p21 CIP1/WAF1 may epigenetically be inactivated in different cancers including breast cancer . In the current study, we demonstrated that application of miR‐302/367 together with miR‐16 can induce upregulation of CDKN1A expression in breast cancer cells.…”

Section: Discussionmentioning

confidence: 66%

miR‐16 enhances miR‐302/367‐induced reprogramming and tumor suppression in breast cancer cells

2020

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Overexpression of either miR‐302 or miR‐302/367 cluster induces reprogramming of cancer cells and exerts tumor‐suppressive effects by induction of mesenchymal‐to‐epithelial transition, apoptosis and a less proliferative capacity. Several reports have described miR‐16 as a tumor suppressor microRNA (miRNA). Here, we studied the impact of exogenous induction of miR‐16 in MDA‐MB‐231 and SK‐BR‐3 breast cancer cells following overexpression of miR‐302/367 cluster and investigated whether transfection of these cells by a mature miR‐16 mimic could affect the reprogramming state of the cells and their tumorigenicity. miR‐16 enhanced the expression levels of OCT4A, SOX2, and NANOG, generally known as transcription or pluripotency factors, and suppressed proliferation and invasiveness of these cells. Meanwhile, inhibition of miR‐16 counteracted both the reprogramming effect and the antitumor function of miR‐302/367 in the breast cancer cells. Current results indicate that miR‐16 can work as an adjuvant to improve both cancer cell reprogramming and tumor‐suppressive function of miR‐302/367 cluster in MDA‐MB‐231 and SK‐BR‐3 cells, while its inhibition counteracts all of these effects. Combined application of miRNAs that share some common targets in cancer cell signaling pathways may provide new approaches for repression of multiple hallmarks of cancer.

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Section: Discussionmentioning

confidence: 66%

miR‐16 enhances miR‐302/367‐induced reprogramming and tumor suppression in breast cancer cells

2020

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“…SFN treatment inhibits the cell proliferation through decreased expression level of Bmi‐1 and Ezh2. In one of our recent finding, we demonstrated that the combinations of green tea polyphenols (GTPs), a dietary DNMTs inhibitor with SFN, reactivate key tumor suppressor genes such as p16 , p21, and Klotho through active chromatin modifications . SFN not only reactivates tumor suppressor genes but also silences the key tumor promoter gene through epigenetic regulations .…”

Section: Sulforaphanementioning

confidence: 99%

Epigenetics of skin cancer: Interventions by selected bioactive phytochemicals

Penta

Somashekar

Meeran

2017

Photoderm Photoimm Photomed

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The prevalence and risk of skin cancer have been increasing over past three decades. Two major types of skin cancer observed in humans are melanoma and nonmelanoma. Nonmelanoma further subdivided into basal cell carcinoma and squamous cell carcinoma. Melanoma arises from melanocyte which locates at the bottom layer of skin epidermis, which primarily protects the skin from being exposed to external factors. Melanoma is less common among all other types of skin cancers but causes higher mortality. Epigenetic regulation associated with the transcriptional activation and inactivation of genes plays a major role in various disease progression including skin cancer. The major epigenetic changes observed at cellular level include DNA methylation, histone modifications, and miRNA-mediated gene regulation. The aberrant pattern in these epigenetic processes leads to altered expression of several genes involved in cell cycle, cell proliferation, cell motility, and apoptosis. Several natural bioactive phytochemicals have been shown to exhibit epigenetic modulatory capability and act as chemopreventive as well as therapeutic agents. In this review, we mainly discuss the major epigenetic modifications observed in melanoma and the epigenetic modulatory role of selected bioactive phytochemicals against the skin cancer.

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“…Genistein 38 is an isoflavone naturally contained in soybean, able to inhibit DNMT and HDAC enzymes and showing anticancer properties in cells . Recently, genistein 38 has been reported to: (i) arrest breast cancer cells cycle in G 2 /M phase inducing the expression of p21 WAF1/CIP1 ; (ii) resensitize estrogen receptor (ER)‐negative breast cancer cells to estrogen‐targeted chemotherapy through the activation of ER; (iii) increase the acetyl‐H3 and acetyl‐H4 levels as well as dimethyl‐ and trimethyl‐H3K4 at the promoter region of the BTG3 gene in renal cancer; (iv) increase the acetylation status of H3K4 at the p21 WAF1/CIP1 and p16 INK4a transcription start sites, mediated by induction of HATs in prostate cancer …”

Section: The Mmt Approachmentioning

confidence: 99%

Epigenetic polypharmacology: A new frontier for epi‐drug discovery

Tomaselli

Lucidi

Rotili

et al. 2019

Medicinal Research Reviews

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Recently, despite the great success achieved by the so‐called “magic bullets” in the treatment of different diseases through a marked and specific interaction with the target of interest, the pharmacological research is moving toward the development of “molecular network active compounds,” embracing the related polypharmacology approach. This strategy was born to overcome the main limitations of the single target therapy leading to a superior therapeutic effect, a decrease of adverse reactions, and a reduction of potential mechanism(s) of drug resistance caused by robustness and redundancy of biological pathways. It has become clear that multifactorial diseases such as cancer, neurological, and inflammatory disorders, may require more complex therapeutic approaches hitting a certain biological system as a whole. Concerning epigenetics, the goal of the multi‐epi‐target approach consists in the development of small molecules able to simultaneously and (often) reversibly bind different specific epi‐targets. To date, two dual histone deacetylase/kinase inhibitors (CUDC‐101 and CUDC‐907) are in an advanced stage of clinical trials. In the last years, the growing interest in polypharmacology encouraged the publication of high‐quality reviews on combination therapy and hybrid molecules. Hence, to update the state‐of‐the‐art of these therapeutic approaches avoiding redundancy, herein we focused only on multiple medication therapies and multitargeting compounds exploiting epigenetic plus nonepigenetic drugs reported in the literature in 2018. In addition, all the multi‐epi‐target inhibitors known in literature so far, hitting two or more epigenetic targets, have been included.

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Epigenetic reactivation of p21CIP1/WAF1 and KLOTHO by a combination of bioactive dietary supplements is partially ERα-dependent in ERα-negative human breast cancer cells

Cited by 42 publications

References 48 publications

miR‐16 enhances miR‐302/367‐induced reprogramming and tumor suppression in breast cancer cells

miR‐16 enhances miR‐302/367‐induced reprogramming and tumor suppression in breast cancer cells

Epigenetics of skin cancer: Interventions by selected bioactive phytochemicals

Epigenetic polypharmacology: A new frontier for epi‐drug discovery

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