Novel Anthraquinone Compounds Induce Cancer Cell Death through Paraptosis

Tian, Wei; Li, Junying; Su, Zhengying; Fu, Lan; Li, Zhaoquan; Liang, Dandan; Wang, Chunmiao; Li, Danrong; Hou, Huaxin

doi:10.1021/acsmedchemlett.8b00624

Cited by 38 publications

(17 citation statements)

References 35 publications

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“…The corresponding carbons were detected in the 13 C NMR spectrum at  = 147.1 and 117.1 ppm, respectively. The reaction of piperidine with 2-chloro-ethanol gave 4 [31][32][33][34] whose reaction with 3 afforded 5 as a colorless solid in 92% isolated yield. Desilylation of 5 with tetra-n-butylammonium fluoride trihydrate in THF yielded 6.…”

Section: Resultsmentioning

confidence: 99%

Unexpected cytotoxicity of a triisopropylsilylated syringaldehyde derived cinnamic acid amide

et al. 2019

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A small series of substituted cinnamic acid amides was prepared and screened for their cytotoxic activity. As a rather astonishing and unprecedented result, compound 5 holding a triisopropylsilyl (TIPS) protecting group at position 4 of the aromatic ring was highly cytotoxic (EC50 = 3.2 mM for HT29 human colon adenocarcinoma cells) while analogs with a methoxy or hydroxyl group at this position were of low cytotoxicity or not cytotoxic at all.

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Section: Resultsmentioning

confidence: 99%

Unexpected cytotoxicity of a triisopropylsilylated syringaldehyde derived cinnamic acid amide

et al. 2019

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“…During the past few decades, both natural and synthetic AQs have been studied for their anticancer properties, and some of them such as doxorubicin, daunorubicin and mitoxantrone are nowadays the rst-line treatment of many cancers [11]. The mechanism of action of AQs includes induction of aberrant cell metabolism, DNA damage, cell cycle arrest, apoptosis [12], paraptosis [13], autophagy [14], radiosensitization [15], decreased metastasis and invasion [16]- [18]. Doxorubicin and mitoxantrone are located in the cell nucleus, which is ascribed to the cationic alkylamino group responsible for its interaction with DNA [19].…”

Section: Introductionmentioning

confidence: 99%

Topical Application of the Anthraquinone Parietin and Blue Light Illumination Induces Delayed Cell Growth and Necrosis in the Deeper Layers of a Subcutaneously Implanted Tumour

Mugas

Calvo

Marioni

et al. 2021

Preprint

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Photodynamic therapy (PDT) is an anticancer treatment involving administration of a tumour-localizing photosensitizer, followed by activation by light of a specific wavelength.In previous work, we showed that the natural anthraquinone (AQ) Parietin (PTN), was a promising photosensitizer for photodynamic therapy of leukemic cells in vitro. The present work aimed to analyze the photosensitizing ability of PTN in the mammary carcinoma LM2 cells in vitro and in vivo in a model of subcutaneously implanted tumours.Photodynamic therapy mediated by Parietin (PTN-PDT) (PTN 30 µM, 1 h and 1.78 J/cm2 of blue light) impaired cell growth and migration of LM2 cells in vitro. PTN per se induced a significant decrease in cell migration, and it was even more marked after illumination (migration index was 0.65 for PTN and 0.30 for PTN-PDT), suggesting that both PTN and parietin-mediated PDT would be potential inhibitors of metastasis.Fluorescence microscopy observation indicated cytoplasmatic localization of the AQ and no fluorescence at all was recorded in the nuclei.When PTN (1.96 mg) dissolved in dimethyl sulfoxide was topically applied on the skin of mice subcutaneously implanted with LM2 cells, PTN orange fluorescence was strongly noticed in the stratum corneum and also in the inner layers of the tumour up to approximately 5 mm. After illumination with 12.74 J/cm2 of blue light, one PDT dose at day 1, induced a significant tumour growth delay at day 3, which was not maintained in time. Therefore, we administered a second PTN-PDT boost on day 3. Under these conditions, the delay of tumour growth was 28 % both on days 3 and 4 of the experiment.Histology of tumours revealed massive tumour necrosis up to 4 mm of depth. Intriguingly, a superficial area of viable tumour in the 1 mm superficial area, and a quite conserved intact skin was evidenced. We hypothesize that this may be due to PTN aggregation in contact with the skin and tumour milieu of the most superficial tumour layers, thus avoiding its photochemical properties.On the other hand, normal skin treated with PTN-PDT exhibited slight histological changes. These preliminary findings encourage further studies of natural AQs administered in different vehicles, for topical treatment of cutaneous malignancies.

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“…Then it causes the release of cytochrome c. Cytochrome c is released into the cytosol and activates a family of caspases. Then a series of cascade reactions are triggered [17][18][19]. Studies have shown that the increased production of reactive oxygen species (ROS) also induces a decrease in the mitochondrial membrane potential, followed by the release of cytochrome c, which ultimately leads to apoptosis [20,21].…”

Section: Introductionmentioning

confidence: 99%

Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway

Guo

Guan

et al. 2020

Molecules

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A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 μg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.

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Novel Anthraquinone Compounds Induce Cancer Cell Death through Paraptosis

Cited by 38 publications

References 35 publications

Unexpected cytotoxicity of a triisopropylsilylated syringaldehyde derived cinnamic acid amide

Unexpected cytotoxicity of a triisopropylsilylated syringaldehyde derived cinnamic acid amide

Topical Application of the Anthraquinone Parietin and Blue Light Illumination Induces Delayed Cell Growth and Necrosis in the Deeper Layers of a Subcutaneously Implanted Tumour

Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway

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