Toward chelerythrine optimization: Analogues designed by molecular simplification exhibit selective growth inhibition in non-small-cell lung cancer cells

Yang, Rosania; Tavares, Maurício Temotheo; Teixeira, Sarah Fernandes; Azevedo, Ricardo A.; Pietro, Diego C.; Fernandes, Thais Batista; Ferreira, Adilson Kleber; Trossini, Gustavo Henrique Goulart; Barbuto, José Alexandre Marzagão; Parise-Filho, Roberto

doi:10.1016/j.bmc.2016.07.065

Cited by 9 publications

(7 citation statements)

References 65 publications

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“…20 In addition, the researchers have found that CHE can induce G1 phase arrest of human leukaemia and NSCLC cells in the F I G U R E 7 Schematic illustration of the underlying mechanism of CHE's anticancer activity recent study. 21,22 This contradiction may be due to the differences of cell types, so the effects of CHE in cell cycle progression should be further studied in more cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…The G2/M phase in cell cycle has potential therapeutic effects as various cancer cells always respond effectively to chemotherapy and/or radiation in this cell period . In addition, the researchers have found that CHE can induce G1 phase arrest of human leukaemia and NSCLC cells in the recent study . This contradiction may be due to the differences of cell types, so the effects of CHE in cell cycle progression should be further studied in more cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

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Chelerythrine induces apoptosis via ROS‐mediated endoplasmic reticulum stress and STAT3 pathways in human renal cell carcinoma

Zhuo

Dai

et al. 2019

J Cellular Molecular Medi

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Renal cell carcinoma (RCC) is a heterogeneous histological disease and it is one of the most common kidney cancer. The treatment of RCC has been improved for the past few years, but its mortality still remains high. Chelerythrine (CHE) is a natural benzo[c]phenanthridine alkaloid and a widely used broad‐range protein kinase C inhibitor which has anti‐cancer effect on various types of human cancer cells. However, its effect on RCC has not been fully elucidated. In this study, we evaluated the effect and mechanism of CHE on RCC cells. Our study showed that CHE induced colony formation inhibition and G2/M cell cycle arrest in a dose‐dependent manner in RCC cells. In addition, CHE increased cellular ROS level, leading to endoplasmic reticulum (ER) stress, inactivating STAT3 activities and inducing apoptosis in RCC cells which were suppressed by NAC, a special ROS inhibitor. We further found that both knockdown of ATF4 protein and overexpression of STAT3 protein could reduce CHE‐induced apoptosis in Caki cells. These results demonstrated that the apoptosis induced by CHE was mediated by ROS‐caused ER stress and STAT3 inactivation. Collectively, our studies provided support for CHE as a potential new therapeutic agent for the management of RCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chelerythrine induces apoptosis via ROS‐mediated endoplasmic reticulum stress and STAT3 pathways in human renal cell carcinoma

Zhuo

Dai

et al. 2019

J Cellular Molecular Medi

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“…As shown in our experimental results, it was also accompanied by significant drug toxicity. Some researchers have enhanced the anti‐tumor effect of CHE and reduced the toxic side effects after structural optimization (Cao et al, 2015; Yang et al, 2016), and some have further reduced the toxic effects of CHE by developing nanomaterials so that CHE can be used for targeted therapy, providing an effective path for the subsequent transformation of CHE (Cao et al, 2016). Although CHE has not been used in human clinical trials, its broad anti‐tumor activity and therapeutic effect on metastasis may provide a new option for clinical treatment in the future.…”

Section: Discussionmentioning

confidence: 99%

Chelerythrine chloride inhibits the progression of colorectal cancer by targeting cancer‐associated fibroblasts through intervention with WNT10B/β‐catenin and TGFβ2/Smad2/3 axis

Liang

Zheng

et al. 2023

Phytotherapy Research

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Chelerythrine chloride (CHE) is a benzodiazepine alkaloid derived from natural herbs with significant anti‐tumor and anti‐inflammatory activities. However, the exact role and underlying mechanisms of CHE in colorectal cancer (CRC) remain unclear. Therefore, this study is aimed to investigate the influence of CHE on the progression of CRC. Cell Counting Kit‐8 assay (CCK‐8), transwell, apoptosis rate, cell cycle distribution, reactive oxygen species (ROS), and colony formation determined the anti‐proliferative activity of CHE in CRC cell lines. Transcriptome sequencing and western blot were used to explore the mechanism. Finally, H&E staining, Ki67, TUNEL, and immunofluorescence were conducted to verify the anti‐CRC activity and potential mechanisms of CHE in vivo. CHE had a prominent inhibitory effect on the proliferation of CRC cells. CHE induces G1 and S phase arrest and induces cell apoptosis by ROS accumulation. Cancer‐associated fibroblasts (CAFs) play a key role in CRC metastasis. Then, this study found that CHE regulates WNT10B/β‐catenin and TGFβ2/Smad2/3 axis, thereby decreasing the expression of α‐SMA, which is a maker of CAFs. Taken together, CHE is a candidate drug and a potent compound for metastatic CRC, which can intervene CAFs in a dual pathway to effectively inhibit the invasion and migration of cancer cells, which can provide a new choice for future clinical treatment.

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“…Additionally, IC50 at intervals ranging from 44 to 143 µg/mL demonstrated synergistic activity with doxorubicin at lower concentrations (1-2 µg/mL), antagonism at higher doses, induced apoptosis of cancer cells (microscopy), and arrest in the G2/ M phase. Moreover, Yang et al 22 established a series of new CHE analogs and evaluated NSCLC cell lines, NCI-H1299, NCI-H292, and NCI-H460. Specifically, they compared the cytotoxicity of these new analogs in NSCLC and non-tumor cell lines (including human umbilical vein endothelial cells and LL24 human lung fibroblasts).…”

Section: Cell Growth Cycle Arrestmentioning

confidence: 99%

“…NSCLC, including A549, NCI-H1299, NCI-H292, and NCI-H460 human umbilical vein endothelial cells and LL24 human lung fibroblastsTo establish a new kind of CHE and its analog, 3fDose-dependent and associated with G0/G1 cell cycle arrestYang et al22 cytochrome c, sary regulators of apoptotic signaling. It was also noted that CHE acts as a Bcl-XL inhibitor and triggers apoptosis by acting directly on mitochondria.…”

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confidence: 99%

Antitumor Effects of Chelerythrine: A Literature Review

Kang

Jiang

Zhang

et al. 2022

Natural Product Communications

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Chelerythrine (CHE), one of the main active components of the medicinal plant, Chelidonium majus, (Figure 1) Botanical authority is traditionally used as a natural medicine for its significant antitumor activity. The relevant literature on the antitumor activity of CHE has been reviewed to provide a theoretical basis for further study and utilization. This review aimed to provide new ideas for developing tumor-targeted drugs.

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Toward chelerythrine optimization: Analogues designed by molecular simplification exhibit selective growth inhibition in non-small-cell lung cancer cells

Cited by 9 publications

References 65 publications

Chelerythrine induces apoptosis via ROS‐mediated endoplasmic reticulum stress and STAT3 pathways in human renal cell carcinoma

Chelerythrine induces apoptosis via ROS‐mediated endoplasmic reticulum stress and STAT3 pathways in human renal cell carcinoma

Chelerythrine chloride inhibits the progression of colorectal cancer by targeting cancer‐associated fibroblasts through intervention with WNT10B/β‐catenin and TGFβ2/Smad2/3 axis

Antitumor Effects of Chelerythrine: A Literature Review

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