Radiosensitivity enhancement of human thyroid carcinoma cells by the inhibitors of histone deacetylase sodium butyrate and valproic acid

Perona, Marina; Thomasz, Lisa; Rossich, Luciano; Rodríguez, C.; Pisarev, Mario A.; Rosemblit, Cinthia; Cremaschi, Graciela; Dagrosa, María Alejandra; Juvenal, Guillermo

doi:10.1016/j.mce.2018.08.007

Cited by 23 publications

(13 citation statements)

References 33 publications

(33 reference statements)

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“…In our study, we found that FK228, a class I HDAC inhibitor, radiosensitized SCLC cells. A previous report showed that HDACi radiosensitized human thyroid cancer cell lines but not the normal thyroid follicular epithelial cells [29]. In line with the selectivity of HDACi for radiosensitizing cancer cells, we observed that FK228 sensitized radioresistant SCLC cells to radiation.…”

Section: Discussionsupporting

confidence: 87%

FK228 sensitizes radioresistant small cell lung cancer cells to radiation

Bian

et al. 2021

Clin Epigenet

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Background Concurrent thoracic radiation plus chemotherapy is the mainstay of first-line treatment for limited-stage small cell lung cancer (LS-SCLC). Despite initial high responsiveness to combined chemo- and radiotherapy, SCLC almost invariably relapses and develops resistance within one year, leading to poor prognosis in patients with LS-SCLC. Developing new chemical agents that increase ionizing radiation’s cytotoxicity against SCLC is urgently needed. Results Dual histone deacetylase (HDAC) and PI3K inhibitor FK228 not only displayed potent anticancer activity, but also enhanced the therapeutic effects of radiotherapy in SCLC cells. Mechanistically, radioresistant SCLC cells exhibit a lower level of histone H3K9 acetylation and a higher expression level of the MRE11-RAD50-NBS1 (MRN) complex and show more efficient and redundant DNA damage repair capacities than radiosensitive SCLC cells. FK228 pretreatment resulted in marked induction of H3k9 acetylation, attenuated homologous recombination (HR) repair competency and impaired non-homologous end joining (NHEJ) repair efficacy, leading to the accumulation of radiation-induced DNA damage and radiosensitization. Conclusion The study uncovered that FK228 sensitized human radioresistant SCLC cells to radiation mainly through induction of chromatin decondensation and suppression of DNA damage signaling and repair. Our study provides a rational basis for a further clinical study to test the potential of FK228 as a radiosensitizing agent to increase the radiation-induced tumor cell kill in LS-SCLC patients.

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Section: Discussionsupporting

confidence: 87%

FK228 sensitizes radioresistant small cell lung cancer cells to radiation

Bian

et al. 2021

Clin Epigenet

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“…The reason is that butyrate inhibits the proliferation of threedimensional colorectal cancer organoids and enhances the radiation-induced cell death in colorectal cancer organoids through FOXO3A.However, butyrate does not increase radiationinduced cell death after irradiation of normal organoids (Park et al, 2020). In vitro experimental studies proved that sodium butyrate and valproic acid can enhance the radiosensitivity of human thyroid cancer cells (Perona et al, 2018).…”

Section: Changes Of Scfas and Radiation-induced Intestinal Injurymentioning

confidence: 99%

Review: Effect of Gut Microbiota and Its Metabolite SCFAs on Radiation-Induced Intestinal Injury

Zhang

Wei

et al. 2021

Front. Cell. Infect. Microbiol.

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Gut microbiota is regarded as the second human genome and forgotten organ, which is symbiotic with the human host and cannot live and exist alone. The gut microbiota performs multiple physiological functions and plays a pivotal role in host health and intestinal homeostasis. However, the gut microbiota can always be affected by various factors and among them, it is radiotherapy that results in gut microbiota 12dysbiosis and it is often embodied in a decrease in the abundance and diversity of gut microbiota, an increase in harmful bacteria and a decrease in beneficial bacteria, thereby affecting many disease states, especially intestine diseases. Furthermore, gut microbiota can produce a variety of metabolites, among which short-chain fatty acids (SCFAs) are one of the most abundant and important metabolites. More importantly, SCFAs can be identified as second messengers to promote signal transduction and affect the occurrence and development of diseases. Radiotherapy can lead to the alterations of SCFAs-producing bacteria and cause changes in SCFAs, which is associated with a variety of diseases such as radiation-induced intestinal injury. However, the specific mechanism of its occurrence is not yet clear. Therefore, this review intends to emphasize the alterations of gut microbiota after radiotherapy and highlight the alterations of SCFAs-producing bacteria and SCFAs to explore the mechanisms of radiation-induced intestinal injury from the perspective of gut microbiota and its metabolite SCFAs.

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“…This demonstrates the incapacity of cells to repair double strand break (DSB) following HDAC inhibition [68,69,70,71]. These observations can be explained by the capacity of HDACi to repress proteins such as Rad50, Ku70 and Ku80, implicated in DDR [71,72]. Others studies showed that TSA, vorinostat and abexinostat can repress BRCA1 (Breast Cancer 1) and RAD51 (Recombination Protein A) expressions [73,74] and thereby inhibit the homologous recombination and the non-homologous recombination end joining DDR mechanisms [70,74,75,76].…”

Section: Effect Of Histone Deacetylase Inhibitors On Tumor Cellsmentioning

confidence: 99%

Epigenetic Drugs for Cancer and microRNAs: A Focus on Histone Deacetylase Inhibitors

Autin

Blanquart

Fradin

2019

Cancers

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Over recent decades, it has become clear that epigenetic abnormalities are involved in the hallmarks of cancer. Histone modifications, such as acetylation, play a crucial role in cancer development and progression, by regulating gene expression, such as for oncogenes or tumor suppressor genes. Therefore, histone deacetylase inhibitors (HDACi) have recently shown efficacy against both hematological and solid cancers. Designed to target histone deacetylases (HDAC), these drugs can modify the expression pattern of numerous genes including those coding for micro-RNAs (miRNA). miRNAs are small non-coding RNAs that regulate gene expression by targeting messenger RNA. Current research has found that miRNAs from a tumor can be investigated in the tumor itself, as well as in patient body fluids. In this review, we summarized current knowledge about HDAC and HDACi in several cancers, and described their impact on miRNA expression. We discuss briefly how circulating miRNAs may be used as biomarkers of HDACi response and used to investigate response to treatment.

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Radiosensitivity enhancement of human thyroid carcinoma cells by the inhibitors of histone deacetylase sodium butyrate and valproic acid

Cited by 23 publications

References 33 publications

FK228 sensitizes radioresistant small cell lung cancer cells to radiation

FK228 sensitizes radioresistant small cell lung cancer cells to radiation

Review: Effect of Gut Microbiota and Its Metabolite SCFAs on Radiation-Induced Intestinal Injury

Epigenetic Drugs for Cancer and microRNAs: A Focus on Histone Deacetylase Inhibitors

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