FGFR2 regulation by picrasidine Q inhibits the cell growth and induces apoptosis in esophageal squamous cell carcinoma

Shi, Yuanyuan; Liu, Xuejiao; Fredimoses, Mangaladoss; Song, Mijung; Chen, Hanyong; Liu, Kangdong; Lee, Mee-Hyun; Dong, Zigang

doi:10.1002/jcb.26385

Cited by 13 publications

(15 citation statements)

References 37 publications

(81 reference statements)

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“…For their bioactivities, C11 was reported as a TMV inhibitor (Chen et al, 2009a) and C12 (KOIKE and OHMOTO, 1986) showed none of anti-inflammatory effects and cytotoxicity against RAW 264.7 cells (Liu P. et al, 2019), while C13 had good cytotoxicity against the human cervical HeLa cell line, with an IC 50 value around 20 μM (Guo et al, 2020). C14 has antihepatoma potential l (Zhao et al, 2019d), and C15 exhibited anti-inflammatory activity (Liu P. et al, 2019) and cytotoxicity against RAW 264.7 (Liu P. et al, 2019), esophageal squamous carcinoma cells (Shi et al, 2018), and also beneficial effects in cerebral protection (Sasaki et al, 2016). From the literatures, C16, C19, C20, and C21 had cytotoxicity against human cervical HeLa, gastric MKN-28 cancer, and mouse melanoma B-16 cancer cells (Jiao et al, 2015), and C21 also strongly inhibited osteoclast formation (Kong et al, 2017).…”

Section: Bioactivity Discussion Of Kumu Compoundsmentioning

confidence: 99%

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Peng

et al. 2021

Front. Pharmacol.

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The stem of Picrasma quassioides (PQ) was recorded as a prominent traditional Chinese medicine, Kumu, which was effective for microbial infection, inflammation, fever, and dysentery, etc. At present, Kumu is widely used in China to develop different medicines, even as injection (Kumu zhusheye), for combating infections. However, the chemical basis of its antimicrobial activity has still not been elucidated. To examine the active chemicals, its stem was extracted to perform bioassay-guided purification against Staphylococcus aureus and Escherichia coli. In this study, two types of columns (normal and reverse-phase) were used for speedy bioassay-guided isolation from Kumu, and the active peaks were collected and identified via an UHPLC-Orbitrap-Ion Trap Mass Spectrometer, combined with MS Fragmenter and ChromGenius. For identification, the COCONUT Database (largest database of natural products) and a manually built PQ database were used, in combination with prediction and calculation of mass fragmentation and retention time to better infer their structures, especially for isomers. Moreover, three standards were analyzed under different conditions for developing and validating the MS method. A total of 25 active compounds were identified, including 24 alkaloids and 1 triterpenoid against S. aureus, whereas only β-carboline-1-carboxylic acid and picrasidine S were active against E. coli. Here, the good antimicrobial activity of 18 chemicals was reported for the first time. Furthermore, the spectrum of three abundant β-carbolines was assessed via their IC50 and MBC against various human pathogens. All of them exhibited strong antimicrobial activities with good potential to be developed as antibiotics. This study clearly showed the antimicrobial chemical basis of Kumu, and the results demonstrated that HRMS coupled with MS Fragmenter and ChromGenius was a powerful tool for compound analysis, which can be used for other complex samples. Beta-carbolines reported here are important lead compounds in antibiotic discovery.

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Section: Bioactivity Discussion Of Kumu Compoundsmentioning

confidence: 99%

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Peng

et al. 2021

Front. Pharmacol.

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“…Although a number of FDA approved therapies, such as growth factor receptor inhibitors and immunotherapies are currently used in clinical settings, none of these therapies are uniformly effective in all patient groups. Thus the hunt for novel therapies remains a constant venture to the research scientists (Shi et al, 2018;Song et al, 2018Song et al, , 2019Xu et al, 2018;Ji et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Xanthohumol Inhibits the Growth of Keratin 18-Overexpressed Esophageal Squamous Cell Carcinoma in vitro and in vivo

Yin

Song

Zhao

et al. 2020

Front. Cell Dev. Biol.

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Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related death worldwide. Xanthohumol is a prenylated flavonoid isolated from hops. Although xanthohumol has been reported to exert anti-obesity, hypoglycemic, anti-hyperlipidemia and anti-cancer activities, the mechanisms underlying its chemotherapeutic activity are yet to be elucidated. In the present study, we found that xanthohumol inhibited ESCC cell proliferation in vitro and in vivo by targeting keratin (KRT)-18. Xanthohumol suppressed the proliferation, foci formation, and anchorage-independent colony growth of KYSE30 cells. Using xanthohumol-sepharose conjugated bead pull-down and mass/mass analysis, we found that KRT18 is a novel target of xanthohumol in KYSE30 cells. KRT18 protein was highly expressed in patient ESCC tissues compared to adjunct tissues. Anti-proliferative activity of xanthohumol was abrogated or enhanced according to the knockdown or overexpression of KRT18 protein, respectively. Xanthohumol also induced apoptosis and cell cycle arrest at G1 phase which was associated with the modulation of expression of related makers including cyclin D1, cyclin D3, and cleaved-PARP, Bcl-2, cytochrome c and Bax. While xanthohumol attenuated KRT18 protein expression, it failed to cause any change in the KRT18 mRNA level. Furthermore, oral administration of xanthohumol decreased tumor volume and weight in patient-derived xenografts (PDXs) tumors having overexpressed KRT18. Overall these results suggest that xanthohumol acts as a KRT18 regulator to suppress the growth of ESCC.

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“…The cell cycle and apoptosis were detected as previously described ( Shi et al, 2018 ). Cells were cultured and treated with DMSO and HF (0.05 and 0.2 μM) in both NCI-H460 and NCI-H1299 for 24 h, followed by single staining with PI (Beyotime) for cell cycle analysis and double staining with PI and Annexin V-FITC (Beyotime) for apoptosis analysis.…”

Section: Methodsmentioning

confidence: 99%

Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways

Zhang

Lan³

et al. 2021

Front. Cell Dev. Biol.

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Lung cancer is the leading cause of cancer death worldwide. Cisplatin is the major DNA-damaging anticancer drug that cross-links the DNA in cancer cells, but many patients inevitably develop resistance with treatment. Identification of a cisplatin sensitizer might postpone or even reverse the development of cisplatin resistance. Halofuginone (HF), a natural small molecule isolated from Dichroa febrifuga, has been found to play an antitumor role. In this study, we found that HF inhibited the proliferation, induced G0/G1 phase arrest, and promoted apoptosis in lung cancer cells in a dose-dependent manner. To explore the underlying mechanism of this antitumor effect of halofuginone, we performed RNA sequencing to profile transcriptomes of NSCLC cells treated with or without halofuginone. Gene expression profiling and KEGG analysis indicated that PI3K/AKT and MAPK signaling pathways were top-ranked pathways affected by halofuginone. Moreover, combination of cisplatin and HF revealed that HF could sensitize the cisplatin-resistant patient-derived lung cancer organoids and lung cancer cells to cisplatin treatment. Taken together, this study identified HF as a cisplatin sensitizer and a dual pathway inhibitor, which might provide a new strategy to improve prognosis of patients with cisplatin-resistant lung cancer.

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FGFR2 regulation by picrasidine Q inhibits the cell growth and induces apoptosis in esophageal squamous cell carcinoma

Cited by 13 publications

References 37 publications

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Xanthohumol Inhibits the Growth of Keratin 18-Overexpressed Esophageal Squamous Cell Carcinoma in vitro and in vivo

Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways

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