Arborinine, a potential LSD1 inhibitor, inhibits epithelial-mesenchymal transition of SGC-7901 cells and adriamycin-resistant gastric cancer SGC-7901/ADR cells

Chu, Yafei; Xiao, Zheng; Jing, Nan; Yan, Wenjuan; Wang, Shanmei; Ma, Bing; Zhang, Jiangfeng; Li, Yang

doi:10.1007/s10637-020-01016-y

Cited by 13 publications

(16 citation statements)

References 23 publications

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“…Among all biological extracts of the plant, Arborinine receives most attention, given its anticancer, anti-malaria, and antiviral effects ( 15 ). Thus far, this NP has not only been extracted and merchandized but also shown potent anticancer activity in a variety of cancers, including gastric cancer ( 12 ), cervical cancer ( 11 ), colorectal cancer ( 10 ), ovarian cancer ( 13 ), and lung cancer ( 16 ). Of note, all those cancer researches indicate that Arborinine exerts anticancer effect via inhibiting the KDM1A (or LSD1) activity, which was also corroborated in ccRCC as reported in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, we have for the first time investigated the role of Arborinine in ccRCC, the major form of renal cell carcinoma. As the anticancer effect of Arborinine and its potential target Lysine Demethylase 1A (KDM1A or LSD1) have been reported in multiple types of cancer ( 12 , 13 ), simply validating such effect and signaling in ccRCC are predictable. We, thus, further studied the signaling transduction downstream of Arborinine and found KDM1A/Ubiquitin-conjugating enzyme E2O (UBE2O) signaling is a potential target.…”

Section: Popular Scientific Summarymentioning

confidence: 99%

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Arborinine from Glycosmis parva leaf extract inhibits clear-cell renal cell carcinoma by inhibiting KDM1A/UBE2O signaling

Feng

Gong

Wang

2022

Food & Nutrition Research

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Background: Arborinine is a natural product isolated from Globigerina parva (G. parva) leaf extract that shows strong anticancer activity with its role in clear-cell renal cell carcinoma (ccRCC) unreported. Objective: We aim to evaluate the role of Arborinine in ccRCC. Design: Arborinine was tested for its effects in ccRCC cell lines in vitro and in silico. Results: Arborinine conferred inhibitory effect to ccRCC cells at reasonable doses. Arborinine showed inhibitory effects on Lysine Demethylase 1A (KDM1A) in ccRCC cells and decreased levels of KDM1A outputs and on epithelial mesenchymal transition (EMT) markers. Arborinine significantly inhibited proliferation, apoptosis, and cell cycle progression and migration of ccRCC cells. Using in silico ChIP analysis and luciferase activity validation, we identified Ubiquitin-conjugating enzyme E2O (UBE2O) as an active transcription target downstream of KDM1A. UBE2O expression was not only correlated with KDM1A expression but also associated with worsened prognosis in ccRCC. Overexpression of UBE2O abrogated cancer-inhibitory effect of Arborinine. Discussion: Arborinine holds promise as an additive in the treatment of ccRCC. Conclusions: We have shown for the first time that Arborinine showed inhibitory effect on ccRCC via KDM1A/UBE2O signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Popular Scientific Summarymentioning

confidence: 99%

Arborinine from Glycosmis parva leaf extract inhibits clear-cell renal cell carcinoma by inhibiting KDM1A/UBE2O signaling

Feng

Gong

Wang

2022

Food & Nutrition Research

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“…It inhibits dose-dependently the proliferation of several cancer cell lines [ 56 , 57 ], triggers cell cycle arrests, blocks cancer cell migration, and induces apoptosis [ 58 , 59 ]. It displays a sub-micromolar activity against drug-resistant SGC-7901 gastric cancer cells resistant to adriamycin (SGC-7901/ADR: IC 50 = 0.24 μM) or to vincristine (SGC-7901/VCR: IC 50 = 1.09 μM) [ 60 ]. Arborinine has been characterized as a selective and reversible inhibitor of histone lysine-specific demethylase 1 (LSD1), an enzyme frequently overexpressed in cancer cells.…”

Section: Bioactive Phytochemicals From R Angustifolia ...mentioning

confidence: 99%

“…Remarkably, the compound was shown to exert a significant antitumor effect in vivo, in two xenografted murine model of gastric cancer (with SGC-7901 cells sensitive or resistant to adriamycin). At the oral dose of 40–80 mg/kg, arborinine reduced tumor growth in mice, without causing any apparent toxicity [ 60 ]. By the same token, very recently arborinine has been shown to suppress ovarian cancer development through inhibition of LSD1.…”

Section: Bioactive Phytochemicals From R Angustifolia ...mentioning

confidence: 99%

Ruta angustifolia Pers. (Narrow-Leaved Fringed Rue): Pharmacological Properties and Phytochemical Profile

Bailly

2023

Plants

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The genus Ruta in the family Rutaceae includes about 40 species, such as the well-known plants R. graveolens L. (common rue) or R. chalepensis L. (fringed rue), but also much lesser-known species such as R. angustifolia Pers. (narrow-leaved fringed rue). This rue specie, originating from the Mediterranean region, is well-distributed in Southeast Asia, notably in the Indo-Chinese peninsula and other territories. In some countries, such as Malaysia, the plant is used to treat liver diseases and cancer. Extracts of R. angustifolia display antifungal, antiviral and antiparasitic effects. Diverse bioactive natural products have been isolated from the aerial parts of the plant, notably quinoline alkaloids and furocoumarins, which present noticeable anti-inflammatory, antioxidant and/or antiproliferative properties. The present review discusses the main pharmacological properties of the plant and its phytoconstituents, with a focus on the anticancer activities evidenced with diverse alkaloids and terpenoids isolated from the aerial parts of the plant. Quinoline alkaloids such as graveoline, kokusaginine, and arborinine have been characterized and their mode of action defined. Arborinine stands as a remarkable inhibitor of histone demethylase LSD1, endowed with promising anticancer activities. Other anticancer compounds, such as the furocoumarins chalepin and rutamarin, have revealed antitumor effects. Their mechanism of action is discussed together with that of other bioactive natural products, including angustifolin and moskachans. Altogether, R. angustifolia Pers. presents a rich phytochemical profile, fully consistent with the traditional use of the plant to treat cancer. This rue species, somewhat neglected, warrant further investigations as a medicinal plant and a source of inspiration for drug discovery and design.

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“…Among the novel LSD1 inhibitors discovered, some performed in a reversible manner. Chu et al identified arborinine as a selective and reversible LSD1 inhibitor with broad-spectrum antiproliferative activity against human gastric cancer cells [25]. Chalcone derivatives [26] and 5-imidazolythieno [3,2-b]pyrroles [27] are other reversible LSD1 inhibitors discovered recently for the treatment of leukemia.…”

mentioning

confidence: 99%

Raloxifene, Identified As a Novel LSD1 Inhibitor, Suppresses the Migration of Renal Cell Carcinoma

Zheng

et al. 2021

Future Med. Chem.

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Aim: As an important epigenetic modulator, histone lysine-specific demethylase 1 (LSD1) has been proved to be associated with the progression of renal cell carcinoma (RCC). Discovering novel LSD1 inhibitors offers therapeutic potential for RCC treatment. Methods & Results: We identified raloxifene as a novel LSD1 inhibitor (IC50 = 2.08 μM) through small compound library screening. Molecular docking indicated raloxifene might bind LSD1 in the flavin adenine dinucleotide (FAD) binding cavity in a reversible manner. Cell viability and migration assays showed raloxifene could suppress the proliferation and migration of RCC cells bearing overexpressed LSD1. Conclusion: Our findings indicated that LSD1 might be a promising therapeutic target for RCC and that raloxifene could serve as a lead compound for further anti-RCC metastasis drug discovery.

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Arborinine, a potential LSD1 inhibitor, inhibits epithelial-mesenchymal transition of SGC-7901 cells and adriamycin-resistant gastric cancer SGC-7901/ADR cells

Cited by 13 publications

References 23 publications

Arborinine from Glycosmis parva leaf extract inhibits clear-cell renal cell carcinoma by inhibiting KDM1A/UBE2O signaling

Arborinine from Glycosmis parva leaf extract inhibits clear-cell renal cell carcinoma by inhibiting KDM1A/UBE2O signaling

Ruta angustifolia Pers. (Narrow-Leaved Fringed Rue): Pharmacological Properties and Phytochemical Profile

Raloxifene, Identified As a Novel LSD1 Inhibitor, Suppresses the Migration of Renal Cell Carcinoma

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