High Levels of Apoptosis Are Induced in the Human Colon Cancer HT-29 Cell Line by Co-Administration of Sulforaphane and a Peptide Nucleic Acid Targeting miR-15b-5p

Gasparello, Jessica; Gambari, Laura; Papi, Chiara; Rozzi, Andrea; Manicardi, Alex; Corradini, Roberto; Gambari, Roberto; Finotti, Alessia

doi:10.1089/nat.2019.0825

Cited by 28 publications

(51 citation statements)

References 55 publications

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“…In addition to the obvious impact of this study on non-invasive CRC diagnostics, our data are of interest for the development of miRNA therapeutics using anti-miRNA molecules against up-regulated miRNAs (such as miR-15b-5p, miR-584-5p and miR-425-3p) or pre-miRNA mimicking the biological functions of down-regulated miRNAs. In this respect we have recently described an antisense molecule inhibiting miR-15b-5p and inducing apoptosis on the CRC cell line HT-29 [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

A Distinctive microRNA (miRNA) Signature in the Blood of Colorectal Cancer (CRC) Patients at Surgery

Gasparello

Papi

Allegretti

et al. 2020

Cancers

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Background: Liquid biopsy (LB) provides an examination of the peripheral blood of cancer patients for circulating tumor cells, cell-free nucleic acids and microRNAs (miRNAs) and is an established tool of precision medicine. Unlike most previous LB studies that focused on advanced metastatic colorectal cancer (CRC), we assessed miRNA dysregulation in blood samples obtained on the day of surgery from patients with primary CRC lesions but no clinical evidence of extra-colonic diffusion. In this study, plasma preparation included miRNAs associated to exosomes, but excluded large macrovesicles from the preparation. Methods: The miRNA profile in plasma isolated from a cohort of 35 CRC patients at the day of surgery was analyzed by Next Generation Sequencing (NGS) and further confirmed by droplet digital RT-PCR (dd-RT-PCR). Results: A miR-141-3p/miR-221-3p/miR-222-3p upregulation signature previously described in advanced CRC did not discriminate the analyzed early-CRC cohort from six tumor-free donors (Tf-D). In contrast, NGS-based miRNome analysis of a training cohort of five CRC and three tumor-free donors identified a novel, distinct nine miRNA signature comprising five up-regulated and four down-regulated miRNAs, six of which could be confirmed in the full CRC and tumor-free donor validation dataset by dd-RT-PCR. Additionally, a KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) mutant status was correlated with the plasma content of three identified miRNAs. Conclusions: When the data obtained were comparatively evaluated, at least one of the miRNAs belonging to the signature list was found to be dysregulated in 34/35 (97.1%) of our early-CRC plasma samples. The miRNA list provides diagnostic markers as well as possible molecular targets for protocols focusing on “microRNA therapeutics”.

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Section: Discussionmentioning

confidence: 99%

A Distinctive microRNA (miRNA) Signature in the Blood of Colorectal Cancer (CRC) Patients at Surgery

Gasparello

Papi

Allegretti

et al. 2020

Cancers

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“…As regards the combined therapy of glioma cells, the authors have recently reported that antitumor drugs can be combined with molecules targeting microRNAs (miRNAs or miRs) (5). miRNAs are short non-coding RNA sequences which, owing to their mechanisms of action, function as gene regulators by repressing the translation or causing the cleavage of the RNA transcripts they target (13)(14)(15).…”

Section: Synergistic Effects Of the Combined Treatment Of U251 And T98g Glioma Cells With An Anti-tubulin Tetrahydrothieno[23-c]pyridine mentioning

confidence: 99%

“…In the development of anticancer approaches, combined treatments appear to be of great interest (1)(2)(3)(4)(5). The idea of combined treatments is based on the possibility to obtain the same biological or therapeutic effect with two or more drugs, using lower concentrations of single drugs.…”

Section: Introductionmentioning

confidence: 99%

“…In this case, the side-effects of the single drug are expected to be limited (1). In addition, the combined therapy of cancer may have an impact on acquired resistance (1,2,5). Furthermore, patient-to-patient variability and independent drug action are sufficient to explain the superior efficacy of drug combinations in the absence of drug synergy or additivity (6).…”

Section: Introductionmentioning

confidence: 99%

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Synergistic effects of the combined treatment of U251 and T98G glioma cells with an anti‑tubulin tetrahydrothieno[2,3‑c]pyridine derivative and a peptide nucleic acid targeting miR‑221‑3p

et al. 2021

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In the development of novel and more effective anticancer approaches, combined treatments appear to be of great interest, based on the possibility of obtaining relevant biological or therapeutic effects using lower concentrations of single drugs. Combination therapy may prove to be of utmost significance in the management of glioblastoma (GBM), a lethal malignancy that accounts for 42% of cancer cases of the central nervous system, with a median survival rate of 15 months. As regards novel therapeutic approaches, the authors have recently demonstrated that peptide nucleic acids (PNAs) that target microRNA (miRNA/miR)-221 are very active in inducing the apoptosis of glioma cells. Furthermore, in a recent study, the authors described two novel series of tubulin polymerization inhibitors based on the 4,5,6,7-tetrahydrothieno[2,3-c]pyridine and 4,5,6,7-tetrahydrobenzo[b]thiophene scaffold, which exerted a potent anti-proliferative effect on a variety of tumor cell lines. The present study aimed to verify the activity on glioblastoma cancer cell lines of one of the most active compounds tested, corresponding to 2-(3' , 4' , 5'-trimethoxyanilino)-3-cyano/alkoxycarbonyl-6-substituted-4 5,6,7-tetrahydrothiene[2,3-c] pyridine (compound 3b), used in combination with an anti-miR-221-3p PNA, already demonstrated to be able to induce high levels of apoptosis. To the best of our knowledge, the results obtained herein demonstrate for the first time a 'combination therapy' performed by the combined use of a PNA targeting miR-221 and the tetrahydrothiene[2,3-c]pyridine derivative 3b, supporting the concept that the combined treatment of GBM cells with a PNA against a specific upregulated oncomiRNA (in the present study a PNA targeting miR-221-3p was used) and anti-tubulin agents (in the present study derivative 3b was used) is an encouraging strategy which may be used to enhance the efficacy of anticancer therapies and at the same time, to reduce side-effects.

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“…In a study on two colon cancer cell lines, SFN treatment has effectively decreased miR-21 and human telomerase reverse transcriptase (hTERT) mRNA levels, by means of epigenetic regulation showing anti-proliferative and apoptosis-inducing effects ( Martin et al, 2018 ). In another recent study on colon cancer cells, the co-treatment of SFN and a miR-15b-5p inhibiting agent, showed very potent anti-apoptotic properties, compared to the two substances alone ( Gasparello et al, 2020 ). In a study on two gastric cancer cell lines and a control cell line, SFN dose-dependently increased miR-9 and miR-326 expression in one cell line.…”

Section: Organosulfur Compoundsmentioning

confidence: 99%

Two Worlds Colliding: The Interplay Between Natural Compounds and Non-Coding Transcripts in Cancer Therapy

et al. 2021

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Cancer is a devastating disease and has recently become the leading cause of death in western countries, representing an immense public health burden. When it comes to cancer treatment, chemotherapy is one of the main pillars, especially for advanced stage tumors. Over the years, natural compounds have emerged as one of the most valuable resources for new chemotherapies. It is estimated that more than half of the currently used chemotherapeutic agents are derived from natural compounds. Usually, natural compounds are discovered empirically and an important limitation of introducing new anti-cancer natural products is lack of knowledge with regard to their mechanism of action. Recent data has proven that several natural compounds may function via modulating the expression and function of non-coding RNAs (ncRNAs). NcRNAs are a heterogenous class of RNA molecules which are usually not translated into proteins but have an important role in gene expression regulation and are involved in multiple tumorigenic processes, including response/resistance to pharmacotherapy. In this review, we will discuss how natural compounds function via ncRNAs while summarizing the available data regarding their effects on over 15 types of cancer. Moreover, we will critically analyze the current advances and limitations in understanding the way natural compounds exert these health-promoting effects by acting on ncRNAs. Finally, we will propose several hypotheses that may open new avenues and perspectives regarding the interaction between natural compounds and ncRNAs, which could lead to improved natural compound-based therapeutic strategies in cancer.

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High Levels of Apoptosis Are Induced in the Human Colon Cancer HT-29 Cell Line by Co-Administration of Sulforaphane and a Peptide Nucleic Acid Targeting miR-15b-5p

Cited by 28 publications

References 55 publications

A Distinctive microRNA (miRNA) Signature in the Blood of Colorectal Cancer (CRC) Patients at Surgery

A Distinctive microRNA (miRNA) Signature in the Blood of Colorectal Cancer (CRC) Patients at Surgery

Synergistic effects of the combined treatment of U251 and T98G glioma cells with an anti‑tubulin tetrahydrothieno[2,3‑c]pyridine derivative and a peptide nucleic acid targeting miR‑221‑3p

Two Worlds Colliding: The Interplay Between Natural Compounds and Non-Coding Transcripts in Cancer Therapy

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