Allyl Isothiocyanate Induces DNA Damage and Impairs DNA Repair in Human Breast Cancer MCF-7 Cells

Liao, Ching-Lung; Peng, Shu‐Fen; Chen, Jaw-Chyun; Chen, Po‐Yuan; Huang, An‐Cheng; Lien, Jin‐Cherng; Chueh, Fu‐Shin; Chiang, Tai‐An; Wu, Pingping; Lin, Kuei‐Ying

doi:10.21873/anticanres.15239

Cited by 13 publications

(6 citation statements)

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“…In colon cancer HT-29 cells, 36 induced apoptosis through ROS-based ER stress and a mitochondria-dependent pathway, in addition to inducing cell cycle arrest in the G2/M phase . In breast cancer MCF-7 cells, 36 demonstrated its apoptotic effect through induction of DNA damage and alteration of DNA repair . Additionally, in prostatic cancer RV1 and PC3 cells, 36 not only promoted apoptosis but also induced autophagy mediated by the up-regulation of beclin-1 .…”

Section: Natural Allylic Compounds and Cancer Therapymentioning

confidence: 97%

“… 151 In breast cancer MCF-7 cells, 36 demonstrated its apoptotic effect through induction of DNA damage and alteration of DNA repair. 152 Additionally, in prostatic cancer RV1 and PC3 cells, 36 not only promoted apoptosis but also induced autophagy mediated by the up-regulation of beclin-1. 153 Furthermore, this allylic compound showed potent cytotoxic activity against CAL27-cisplatin-resistant human oral cancer cells, including the inhibition of Akt/mTOR signaling and the induction of mitochondria-dependent apoptosis through up-regulation of caspases-3 and -9.…”

Section: Natural Allylic Compounds and Cancer Therapymentioning

confidence: 99%

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From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment

et al. 2023

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Since the beginning of history, natural products have been an abundant source of bioactive molecules for the treatment of different diseases, including cancer. Many allyl derivatives, which have shown anticancer activity both in vitro and in vivo in a large number of cancers, are bioactive molecules found in garlic, cinnamon, nutmeg, or mustard. In addition, synthetic products containing allyl fragments have been developed showing potent anticancer properties. Of particular note is the allyl derivative 17-AAG, which has been evaluated in Phase I and Phase II/III clinical trials for the treatment of multiple myeloma, metastatic melanoma, renal cancer, and breast cancer. In this Perspective, we compile extensive literature evidence with descriptions and discussions of the most recent advances in different natural and synthetic allyl derivatives that could generate cancer drug candidates in the near future.

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Section: Natural Allylic Compounds and Cancer Therapymentioning

confidence: 97%

Section: Natural Allylic Compounds and Cancer Therapymentioning

confidence: 99%

From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment

et al. 2023

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“…Numerous preclinical studies have shown that AITC has pharmacological activities such as antimicrobial, 20 antioxidant, 21 chemoprevention, 22–24 antiobesity, 25,26 anti‐inflammatory, 27,28 and anticancer 29,30 activities. Recently, our earlier studies have shown that AITC‐induced DNA damage and affects DNA repair‐associated protein expression in human colon cancer cells in vitro 31 . But, there is no available information to show AITC affect cell DNA damage and repair in gastric cancer, thus, we investigate the effects of AITC on DNA damage and repair in human gastric cancer AGS and SNU‐1 cells.…”

Section: Introductionmentioning

confidence: 93%

“…After cells were incubated with DAPI, all samples were mounted on glass slides before observed with a cover slide, snapped using a fluorescence microscope (Nikon ECLIPSE Ni-U) at 200Â and were calculated the head intensity (fold of control) as described previously. 31…”

Section: Cell Proliferation Changes In Human Gastric Cancer Cellsmentioning

confidence: 99%

“…Recently, our earlier studies have shown that AITC-induced DNA damage and affects DNA repair-associated protein expression in human colon cancer cells in vitro. 31 But, there is no available information to show AITC affect cell DNA damage and repair in gastric cancer, thus, we investigate the effects of AITC on DNA damage and repair in human gastric cancer AGS and SNU-1 cells. We found that AITC significantly induced DNA damage and affect DNA repair in both AGS and SNU-1 cells in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Allyl isothiocyanate induces DNA damage and inhibits DNA repair‐associated proteins in a human gastric cancer cells in vitro

Shih,

Hsu,

Lai

et al. 2023

Environmental Toxicology

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Allyl isothiocyanate (AITC) is abundant in cruciferous vegetables and it present pharmacological activity including anticancer activity in many types of human cancer cells in vitro and in vivo. Currently, no available information to show AITC affecting DNA damage and repair‐associated protein expression in human gastric cancer cells. Therefore, in the present studies, we investigated AITC‐induced cytotoxic effects on human gastric cancer in AGS and SNU‐1 cells whether or not via the induction of DNA damage and affected DNA damage and repair associated poteins expressions in vitro. Cell viability and morphological changes were assayed by flow cytometer and phase contrast microscopy, respectively, the results indicated AITC induced cell morphological changes and decreased total viable cells in AGS and SNU‐1 cells in a dose‐dependently. AITC induced DNA condensation and damage in a dose‐dependently which based on the cell nuclei was stained by 4′, 6‐diamidino‐2‐phenylindole present in AGS and SNU‐1 cells. DNA damage and repair associated proteins expression in AGS and SNU‐1 cells were measured by Western blotting. The results indicated AITC decreased nuclear factor erythroid 2‐related factor 2 (NRF2), heme oxygenase‐1 (HO‐1), glutathione, and catalase, but increased superoxide dismutase (SOD (Cu/Zn)), and nitric oxide synthase (iNOS) in AGS cells, however, in SNU‐1 cells are increased HO‐1. AITC increased DNA‐dependent protein kinase (DNA‐PK), phosphorylation of gamma H2A histone family member X on Ser139 (γH2AXpSer139), and heat shock protein 90 (HSP90) in AGS cells. AITC increased DNA‐PK, mediator of DNA damage checkpoint protein 1 (MDC1), γH2AXpSer139, topoisomerase II alpha (TOPIIα), topoisomerase II beta (TOPIIβ), HSP90, and heat shock protein 70 (HSP70) in SNU‐1 cells. AITC increased p53, p53pSer15, and p21 but decreased murine double minute 2 (MDM2)pSer166 and O6‐methylguanine‐DNA methyltransferase (MGMT) in AGS cells; however, it has a similar effect of AITC except increased ataxia telangiectasia and Rad3‐related protein (ATR)pSer428, checkpoint kinase 1 (CHK1), and checkpoint kinase 2 (CHK2) in SNU‐1 cells. Apparently, both cell responses to AITC are different, nonetheless, all of these observations suggest that AITC inhibits the growth of gastric cancer cells may through induction off DNA damage in vitro.

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Covalent Isothiocyanate Inhibitors of Macrophage Migration Inhibitory Factor as Potential Colorectal Cancer Treatments

Putha,

Kok,

Fellner

et al. 2024

ChemMedChem

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Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with roles in innate and adaptive human immune responses, as well as inflammation. MIF exerts its biological activity by binding to the cell surface receptor CD74 as well as intracellular signalling proteins. MIF also possesses keto‐enol tautomerase activity. Inhibition of the tautomerase activity has been associated with loss of biological activity of MIF and a potential anticancer target. Isothiocyanates (ITCs) are a class of compounds present in cruciferous vegetables that inhibit the MIF tautomerase activity via covalent modification of the N‐terminal proline. A range of substituted ITCs featuring benzyl, phenethyl and phenyl propyl isothiocyanates were designed, synthesised and tested to determine any structure activity relationship for inhibiting MIF. Crystal structures of covalent compounds 8 and 9 in complex with rhMIF revealed key hydrogen bonding and edge‐to‐face π stacking interactions. Compound 9 and 11 with sub micromolar activity were tested in the NCI60 cancer cell lines panel. Both compounds showed tissue‐specific reduced growth in colon and renal cancer cell lines, while one of these showed potent, dose‐dependent inhibition of growth against all seven colon cancer cell lines (GI50 < 2.5 µM) and all eight renal cancer cell lines (GI50 < 2.2 µM).

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Allyl Isothiocyanate Induces DNA Damage and Impairs DNA Repair in Human Breast Cancer MCF-7 Cells

Cited by 13 publications

References 0 publications

From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment

From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment

Allyl isothiocyanate induces DNA damage and inhibits DNA repair‐associated proteins in a human gastric cancer cells in vitro

Covalent Isothiocyanate Inhibitors of Macrophage Migration Inhibitory Factor as Potential Colorectal Cancer Treatments

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