Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma

Mitsiogianni, Melina; Mantso, Theodora; Trafalis, Dimitrios T.; Rupasinghe, H.P. Vasantha; Zoumpourlis, Vassilios; Franco, Rodrigo; Botaitis, Sotirios; Pappa, Aglaia; Panayiotidis, Mihalis Ι.

doi:10.1007/s00394-019-01925-6

Cited by 25 publications

(21 citation statements)

References 65 publications

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“…Cruciferous vegetables are widely and often frequently consumed by humans (9), and a high dietary intake of these vegetables has been considered to be associated with a low risk of CRC in the involvement of epigenetic regulation (6,41). Moreover, abundant glucosinolates and their hydrolysis products, such as indoles and isothiocyanates (ITCs), are included (7,8). Allyl isothiocyanate (AITC) belongs to the ITC family and exerts several vital biological effects, including antitumor and anticancer cell proliferation effects on cultured cancer cell lines and animal tumor models (13,42).…”

Section: Discussionmentioning

confidence: 99%

“…Numerous epidemiological studies have observed an inverse association between cancers and high dietary consumption of cruciferous vegetables, which is recognized to confer health benefits for reducing the risk of developing the disease and eliciting chemopreventive effects ( 6 ). Cruciferae is a family of vegetables, including broccoli, cabbage, cauliflower, and brussels sprouts, which are rich in isothiocyanates (ITCs), a nutraceutical agent with protection against cancer development ( 7 , 8 ). Moreover, ITCs have drawn attention owing to their capability to exert a broad spectrum of antitumor effects ( 9 – 11 ).…”

Section: Introductionmentioning

confidence: 99%

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Sensitivity of allyl isothiocyanate to induce apoptosis via ER stress and the mitochondrial pathway upon ROS production in colorectal adenocarcinoma cells

Chiang¹,

Tsai

Hsu

et al. 2020

Oncol Rep

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Allyl isothiocyanate (AITC), a bioactive phytochemical compound that is a constituent of dietary cruciferous vegetables, possesses promising chemopreventive and anticancer effects. However, reports of AITC exerting antitumor effects on apoptosis induction of colorectal cancer (CRC) cells in vitro are not well elucidated. The present study focused on the functional mechanism of the endoplasmic reticulum (ER) stress-based apoptotic machinery induced by AITC in human colorectal cancer HT-29 cells. Our results indicated that AITC decreased cell growth and number, reduced viability, and facilitated morphological changes of apoptotic cell death. DNA analysis by flow cytometry showed G2/M phase arrest, and alterations in the modulated protein levels caused by AITC were detected via western blot analysis. AITC also triggered vital intrinsic apoptotic factors (caspase-9/caspase-3 activity), disrupted mitochondrial membrane potential, and stimulated mitochondrial-related apoptotic molecules (e.g., cytochrome c, apoptotic protease activating factor 1, apoptosis-inducing factor, and endonuclease G). Additionally, AITC prompted induced cytosolic Ca 2+ release and Ca 2+-dependent ER stress-related signals, such as calpain 1, activating transcription factor 6α, glucose-regulated proteins 78 and 94, growth arrest-and DNA damage-inducible protein 153 (GADD153), and caspase-4. The level of reactive oxygen species (ROS) production was found to induce the hallmark of ER stress GADD153, proapoptotic marker caspase-3, and calpain activity after AITC treatment. Our findings showed for the first time that AITC induced G2/M phase arrest and apoptotic death via ROS-based ER stress and the intrinsic pathway (mitochondrial-dependent) in HT-29 cells. Overall, AITC may exert an epigenetic effect and is a potential bioactive compound for CRC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sensitivity of allyl isothiocyanate to induce apoptosis via ER stress and the mitochondrial pathway upon ROS production in colorectal adenocarcinoma cells

Chiang¹,

Tsai

Hsu

et al. 2020

Oncol Rep

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“…Untreated (control) cells were incubated with either 0.1% DMSO or 0.1% EtOH. The density of seeded cells was determined as previously published [ 16 , 17 ].…”

Section: Methodsmentioning

confidence: 99%

“…In addition, the observed side effects caused by systemic toxicity, along with drug resistance, can further contribute to the limited therapeutic efficacy against MM [ 6 , 11 , 15 ]. To this end, the development of new therapeutic approaches is of high importance in order to improve current existing protocols, thereby improving the quality of life in MM patients [ 6 , 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

An Evaluation of the Anti-Carcinogenic Response of Major Isothiocyanates in Non-Metastatic and Metastatic Melanoma Cells

et al. 2021

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Malignant melanoma is one of the most deadly types of solid cancers, a property mainly attributed to its highly aggressive metastatic form. On the other hand, different classes of isothiocyanates, a class of phytochemicals, present in cruciferous vegetables have been characterized by considerable anti-cancer activity in both in vitro and in vivo experimental models. In the current study, we investigated the anti-cancer response of five isothiocyanates in an in vitro model of melanoma consisting of non-metastatic (A375, B16F-10) and metastatic (VMM1, Hs294T) malignant melanoma as well as non-melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte-neighboring keratinocyte (HaCaT) cells. Our aim was to compare different endpoints of cytotoxicity (e.g., reactive oxygen species, intracellular glutathione content, cell cycle growth arrest, apoptosis and necrosis) descriptive of an anti-cancer response between non-metastatic and metastatic melanoma as well as non-melanoma epidermoid carcinoma and non-tumorigenic cells. Our results showed that exposure to isothiocyanates induced an increase in intracellular reactive oxygen species and glutathione contents between non-metastatic and metastatic melanoma cells. The distribution of cell cycle phases followed a similar pattern in a manner where non-metastatic and metastatic melanoma cells appeared to be growth arrested at the G2/M phase while elevated levels of metastatic melanoma cells were shown to be at sub G1 phase, an indicator of necrotic cell death. Finally, metastatic melanoma cells were more sensitive apoptosis and/or necrosis as higher levels were observed compared to non-melanoma epidermoid carcinoma and non-tumorigenic cells. In general, non-melanoma epidermoid carcinoma and non-tumorigenic cells were more resistant under any experimental exposure condition. Overall, our study provides further evidence for the potential development of isothiocyanates as promising anti-cancer agents against non-metastatic and metastatic melanoma cells, a property specific for these cells and not shared by non-melanoma epidermoid carcinoma or non-tumorigenic melanocyte cells.

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“…Moreover, the effect of AITC on lysine acetylation and methylation marks on histones H3 and H4 have been explored recently. To this end, exposure of A375 cells to 10 μM of AITC decreased HDAC and histone acetyl transferase (HAT) activities, while also affecting the acetylated and methylated content of histones (by means of assessing specific lysine modifications), suggesting that AITC can exert an epigenetically-induced anti-melanoma activity [313].…”

Section: Itcs As Anti-melanoma Agentsmentioning

confidence: 99%

The Role of Isothiocyanates as Cancer Chemo-Preventive, Chemo-Therapeutic and Anti-Melanoma Agents

et al. 2019

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Many studies have shown evidence in support of the beneficial effects of phytochemicals in preventing chronic diseases, including cancer. Among such phytochemicals, sulphur-containing compounds (e.g., isothiocyanates (ITCs)) have raised scientific interest by exerting unique chemo-preventive properties against cancer pathogenesis. ITCs are the major biologically active compounds capable of mediating the anticancer effect of cruciferous vegetables. Recently, many studies have shown that a higher intake of cruciferous vegetables is associated with reduced risk of developing various forms of cancers primarily due to a plurality of effects, including (i) metabolic activation and detoxification, (ii) inflammation, (iii) angiogenesis, (iv) metastasis and (v) regulation of the epigenetic machinery. In the context of human malignant melanoma, a number of studies suggest that ITCs can cause cell cycle growth arrest and also induce apoptosis in human malignant melanoma cells. On such basis, ITCs could serve as promising chemo-therapeutic agents that could be used in the clinical setting to potentiate the efficacy of existing therapies.

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Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma

Cited by 25 publications

References 65 publications

Sensitivity of allyl isothiocyanate to induce apoptosis via ER stress and the mitochondrial pathway upon ROS production in colorectal adenocarcinoma cells

Sensitivity of allyl isothiocyanate to induce apoptosis via ER stress and the mitochondrial pathway upon ROS production in colorectal adenocarcinoma cells

An Evaluation of the Anti-Carcinogenic Response of Major Isothiocyanates in Non-Metastatic and Metastatic Melanoma Cells

The Role of Isothiocyanates as Cancer Chemo-Preventive, Chemo-Therapeutic and Anti-Melanoma Agents

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