Camalexin, an indole phytoalexin, inhibits cell proliferation, migration, and mammosphere formation in breast cancer cells via the aryl hydrocarbon receptor

Yamashita, Naoya; Taga, Chiharu; Ozawa, Moeno; Kanno, Yuichiro; Sanada, Noriko; Kizu, Ryoichi

doi:10.1007/s11418-021-01560-8

Cited by 16 publications

(15 citation statements)

References 37 publications

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“… These phytoalexins bearing different ring systems, such as 1,3-thiazine, 1,3-thiazole, and 1,2-thiazole, have different biological activities. In these sulfur-containing heterocyclic compounds, thiazoles are important five-membered heterocyclic rings with a broad spectrum of activities such as antibiotic, antineoplastic, antimicrobial, and anti-inflammatory activities. , …”

Section: Introductionmentioning

confidence: 99%

“…thaliana leaves infected by Pseudomonas syringae can also produce camalexin . The biosynthesis of camalexin can be induced by various plant pathogens including fungi, bacteria, oomycetes, viruses, and so forth. − The biological activity of the Brassicaceae defense compound camalexin is not confined to plant protection; it also showed antiproliferative activity against the human breast cancer cell line ,, and human T-leukemia Jurkat cells, cytotoxic activity against Trypanosoma cruzi, and so on. As a Brassicaceae defense compound, camalexin can also be transformed into N-1- or C-6-glycosylated derivatives in leaves .…”

Section: Introductionmentioning

confidence: 99%

“…In these sulfur-containing heterocyclic compounds, thiazoles are important five-membered heterocyclic rings with a broad spectrum of activities such as antibiotic, antineoplastic, antimicrobial, and antiinflammatory activities. 6,7 Camalexin is an important phytoalexin of cruciferous plants Arabidopsis thaliana and Camelina sativa. 8 It was isolated from C. sativa leaves for the first time in 1991 (Figure 1).…”

Section: ■ Introductionmentioning

confidence: 99%

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Discovery of Phytoalexin Camalexin and Its Derivatives as Novel Antiviral and Antiphytopathogenic-Fungus Agents

Liao

Wang

et al. 2022

J. Agric. Food Chem.

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In response to the invasion of plant viruses and pathogenic fungi, higher plants produce defensive allelochemicals. Finding candidate varieties of botanical pesticides based on allelochemicals is one of the important ways to create efficient and green pesticides. Here, a series of camalexin derivatives based on a phytoalexin camalexin scaffold were designed, synthesized, and assessed for their antiviral and fungicidal activities systematically. Most of these camalexin derivatives exhibited better antiviral activities against tobacco mosaic virus (TMV) than the control antiviral agent ribavirin. Under the same test conditions, the anti-TMV activities of compounds 3d, 5a, 5d, and 10f−10h were found to be equivalent to or better than that of ningnanmycin, an agricultural cytosine nucleoside antibiotic with excellent protective effect. The antiviral mechanism research showed that compound 5a could cause 20S CP disk fusion and disintegration, thus affecting the assembly of virus particles. The results of molecular docking indicate that there were obvious hydrogen bonds between compounds 3d, 5a, and 10f and TMV CP. The binding constants of compounds 5a and 10f to TMV CP were also calculated using fluorescence titration. These camalexin derivatives also presented broad spectrum fungicidal activities, especially for Rhizoctonia solani and Physalospora piricola. In this work, the design, synthesis, structure optimization, and mode of action of camalexin derivatives were carried out progressively. This work provides a reference for using defensive chemical compounds as novel pesticide lead compounds.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Discovery of Phytoalexin Camalexin and Its Derivatives as Novel Antiviral and Antiphytopathogenic-Fungus Agents

Liao

Wang

et al. 2022

J. Agric. Food Chem.

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“…Previous reports, including our studies, have established the anti-tumorigenic ability of agonist-activated AHR [ 46 ]. Agonist-mediated AHR activation represses mammosphere formation and reduces the ALDH-high population, suggesting the repressive effects of AHR on breast CSCs [ 47 , 48 , 49 , 50 ]. Moreover, we have previously reported the suppressive effect of AHR (depending on the agonist used) on mammosphere formation in BC cells [ 22 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Possible Involvement of the Upregulation of ΔNp63 Expression Mediated by HER2-Activated Aryl Hydrocarbon Receptor in Mammosphere Maintenance

Kanno

Saito

Yamashita

et al. 2022

IJMS

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Cancer stem cells (CSCs) contribute to the drug resistance, recurrence, and metastasis of breast cancers. Recently, we demonstrated that HER2 overexpression increases mammosphere formation via the activation of aryl hydrocarbon receptor (AHR). In this study, the objective was to identify the mechanism underlying mammosphere maintenance mediated by HER2 signaling-activated AHR. We compared the chromatin structure of AHR-knockout (AHRKO) HER2-overexpressing MCF-7 (HER2-5) cells with that of wild-type HER2-5 cells; subsequently, we identified TP63, a stemness factor, as a potential target gene of AHR. ∆Np63 mRNA and protein levels were higher in HER2-5 cells than in HER2-5/AHRKO cells. Activation of HER2/HER3 signaling by heregulin treatment increased ∆Np63 mRNA levels, and its induction was decreased by AHR knockdown in HER2-5 cells. The results of the chromatin immunoprecipitation assay revealed an interaction between AHR and the intronic region of TP63, which encodes ∆Np63. A luciferase reporter gene assay with the intronic region of TP63 showed that AHR expression increased reporter activity. Collectively, our findings suggest that HER2-activated AHR upregulates ∆Np63 expression and that this signaling cascade is involved in CSC maintenance in HER2-expressing breast cancers.

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“…Camalexin (3-thiazol-2-yl-indole) is an indole alkaloid phytoalexin, which is induced by phytopathogens and accumulates in various Brassicaceae plant organs or tissues. Many studies have characterized that camalexin and its derivatives have been found to possess significant anticancer, antifungal, antiviral, and antibacterial activities [ 36 ]. Camalexin biosynthesis is dependent on cysteine, and glutathione reduced form (GSH) is the direct precursor of the thiazole ring [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Aminothiazole Derivatives as Promising Antiviral, Antioxidant and Antibacterial Candidates

Minickaitė

Grybaitė

Vaickelionienė

et al. 2022

IJMS

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It is well-known that thiazole derivatives are usually found in lead structures, which demonstrate a wide range of pharmacological effects. The aim of this research was to explore the antiviral, antioxidant, and antibacterial activities of novel, substituted thiazole compounds and to find potential agents that could have biological activities in one single biomolecule. A series of novel aminothiazoles were synthesized, and their biological activity was characterized. The obtained results were compared with those of the standard antiviral, antioxidant, antibacterial and anticancer agents. The compound bearing 4-cianophenyl substituent in the thiazole ring demonstrated the highest cytotoxic properties by decreasing the A549 viability to 87.2%. The compound bearing 4-trifluoromethylphenyl substituent in the thiazole ring showed significant antiviral activity against the PR8 influenza A strain, which was comparable to the oseltamivir and amantadine. Novel compounds with 4-chlorophenyl, 4-trifluoromethylphenyl, phenyl, 4-fluorophenyl, and 4-cianophenyl substituents in the thiazole ring demonstrated antioxidant activity by DPPH, reducing power, FRAP methods, and antibacterial activity against Escherichia coli and Bacillus subtilis bacteria. These data demonstrate that substituted aminothiazole derivatives are promising scaffolds for further optimization and development of new compounds with potential influenza A-targeted antiviral activity. Study results could demonstrate that structure optimization of novel aminothiazole compounds may be useful in the prevention of reactive oxygen species and developing new specifically targeted antioxidant and antibacterial agents.

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Camalexin, an indole phytoalexin, inhibits cell proliferation, migration, and mammosphere formation in breast cancer cells via the aryl hydrocarbon receptor

Cited by 16 publications

References 37 publications

Discovery of Phytoalexin Camalexin and Its Derivatives as Novel Antiviral and Antiphytopathogenic-Fungus Agents

Discovery of Phytoalexin Camalexin and Its Derivatives as Novel Antiviral and Antiphytopathogenic-Fungus Agents

Possible Involvement of the Upregulation of ΔNp63 Expression Mediated by HER2-Activated Aryl Hydrocarbon Receptor in Mammosphere Maintenance

Synthesis of Novel Aminothiazole Derivatives as Promising Antiviral, Antioxidant and Antibacterial Candidates

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