Esculetin induces cell cycle arrest and apoptosis in human colon cancer LoVo cells

Choi, Yong Jun; Lee, Chang M.; Park, See‐Hyoung; Nam, Myeong Jin

doi:10.1002/tox.22815

Cited by 25 publications

(37 citation statements)

References 37 publications

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“…Molecular analysis of the mechanisms by which the ethanolic extract induced cell death suggested a double pathway based on apoptosis mediated by caspases and autophagy. Recent studies showed that esculetin alone inhibited proliferation in LoVo colon cancer cells, inducing arrest in the G0/G1 phase and increasing the propapoptotic proteins caspase 3, 7, and 9 [50,51]. Similar results were obtained by Wang et al [52] in leukemia cell lines, which exhibited apoptosis and autophagy after treatment with esculetin.…”

Section: Discussionsupporting

confidence: 76%

Antitumor Effect of the Ethanolic Extract from Seeds of Euphorbia lathyris in Colorectal Cancer

et al. 2021

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The seeds of Euphorbia lathyris have been used in traditional medicine to treat various medical conditions. However, neither all of their active biocompounds nor the molecular mechanisms underlying their therapeutic effects have been described. A new ethanolic extract of defatted flour from mature seeds of Euphorbia lathyris showed a high total polyphenol content and significant antioxidant activity. Chromatographic analysis showed that esculetin, euphorbetin, gaultherin, and kaempferol-3-rutinoside were the most abundant polyphenolic bioactive compounds. Antiproliferative assays showed a high and selective antitumor activity against colon cancer cell lines (T84 and HCT-15). In addition, a significant antiproliferative activity against glioblastoma multiforme cells was also demonstrated. Its mechanism of action to induce cell death was mediated by the overexpression of caspases 9, 3, and 8, and by activation of autophagy. Interestingly, a reduction in the migration capacity of colon cancer cells and a significant antiangiogenic effect on human umbilical vein endothelial cells were also demonstrated. Finally, the extract significantly reduced the subpopulations of cancer stem cells. This extract could be the basis to develop new therapeutic strategies for the treatment of colon cancer, although further experiments will be necessary to determine its in vivo effects.

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Section: Discussionsupporting

confidence: 76%

Antitumor Effect of the Ethanolic Extract from Seeds of Euphorbia lathyris in Colorectal Cancer

et al. 2021

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“…Previously, we reported that Esculetin, which is natural compound derived from Artemisia capillaris , Citrus limonia , and Euphorbia lathyris , induced cell cycle arrest and apoptosis in human colon cancer LoVo cells 51 . In that study, we showed the antiproliferative effects of Esculetin in LoVo cells, which was associated with upregulation of p53 expression.…”

Section: Discussionmentioning

confidence: 78%

6,8‐Diprenylorobol induces apoptosis in human colon cancer cells via activation of intracellular reactive oxygen species and p53

Choi

Lee

et al. 2020

Environmental Toxicology

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6,8‐Diprenylorobol is a natural compound mainly found in Glycyrrhiza uralensis fisch and Maclura tricuspidata, which has been used traditionally as food and medicine in Asia. So far, the antiproliferative effect of 6,8‐diprenylorobol has not been studied yet in colon cancer. In this study, we aimed to evaluate the antiproliferative effects of 6,8‐diprenylorobol in LoVo and HCT15, two kinds of human colon cancer cells. 6,8‐Diprenylorobol inhibited the proliferation of LoVo and HCT15 cells in a dose‐ and time‐dependent manner. A 40 μM of 6,8‐diprenylorobol for 72 h reduced both of cell viability under 50%. After treatment of 6,8‐diprenylorobol (40 and 60 μM) for 72 h, late apoptotic cell portion in LoVo and HCT15 cells were 24, 70% and 13, 90%, respectively, which was confirmed by checking DNA fragmentation in both cells. Mechanistically, 6,8‐diprenylorobol activated p53 and its phosphorylated form (Ser15, Ser20, and Ser46) expression but suppressed Akt and mitogen‐activated protein kinases (MAPKs) phosphorylation in LoVo and HCT15 cells. Interestingly, 6,8‐diprenylorobol induced the generation of intracellular reactive oxygen species (ROS), which was attenuated with N‐acetyl cysteine (NAC) treatment. Compared to the control, 60 μM of 6,8‐diprenylorobol caused to increase ROS level to 210% in LoVo and HCT15, which was reduced into 161% and 124%, respectively with NAC. Furthermore, cell viability and apoptotic cell portion by 6,8‐diprenylorobol was recovered by incubation with NAC. Taken together, these results indicate that 6,8‐diprenylorobol has the potential antiproliferative effect against LoVo and HCT15 colon cancer cells through activation of p53 and generation of ROS.

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“…However, in malignant cells, aberrant expression of cell cycle regulators attenuates the differentiation of cells that results in irregular cell growth. In the recent past, numerous reports have suggested that natural compounds have antiproliferative activity by triggering cell cycle arrest ( 48 ). Luo et al .…”

Section: Resultsmentioning

confidence: 99%

“…, which consists of four distinct progressive phases (subG1/G0, G1, S, and G2/M)(47).Under normal circumstances, the progression of the cell cycle is tightly regulated by a cascade activation of cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors. However, in malignant cells, aberrant expression of cell cycle regulators attenuates the differentiation of cells that results in irregular cell growth.…”

mentioning

confidence: 99%

Tamarix articulata Inhibits Cell Proliferation, Promotes Cell Death Mechanisms and Triggers G0/G1 Cell Cycle Arrest in Hepatocellular Carcinoma Cells

Alnuqaydan

2021

Food Technol. Biotechnol. (Online)

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Research background. From ancient times plants have been used for medicinal purposes against various ailments. In the modern era, plants are a major source of drugs and are an appealing drug candidate for the anticancer therapeutics against various molecular targets. Here we tested Tamarix articulata methanolic extract of dry leaves for anticancer activity against a panel of hepatocellular carcinoma cells. Experimental approach. Cell viability of hepatocellular carcinoma cells was determined by MTT assay after dose-dependent treatment with extract of Tamarix articulata. Phase-contrast microscopy and DAPI staining were performed to analyze cellular and nuclear morphology. Immunoblotting was performed to determine the expression of proteins associated with autophagy, apoptosis, and cell cycle. However, flow cytometry was used for the quantification of apoptotic cells and the analysis of cells in different phases of the cell cycle after treatment with varying doses of Tamarix articulata. Additionally, acridine orange staining and DCFHDA dye were used to analyze the quantification of autophagosomes and reactive oxygen species. Results and conclusion. Our results demonstrate that Tamarix articulata methanolic extract exhibits promising antiproliferative activity with IC50 values (271±4.38), (298±7.08) and (336±6.11) µg/mL against HepG2, Huh7D12, and Hep3B cell lines, respectively. Mechanistically, we found Tamarix articulata methanolic extract induces cell death by activating apoptosis and autophagy pathways. First, Tamarix articulata methanolic extract promotes autophagy which was confirmed by acridine orange staining. The immunoblotting analysis further confirms that Tamarix articulata methanolic extract consistently induces the conversion of, LC3I to LC3II form with a gradual decrease in expression of autophagy substrate protein p62 at higher doses. Second, Tamarix articulata methanolic extract promotes reactive oxygen species production in hepatocellular carcinoma cells and activates reactive oxygen species-mediated apoptosis. Flow cytometry and immunoblotting analysis showed that Tamarix articulata methanolic extract induces dose-dependent apoptosis and activates proapoptotic proteins caspase-3 and PARP1. Additionally, Tamarix articulata methanolic extract triggers the arrest of the G0/G1 phase of the cell cycle and upregulates the protein expression of p27/Kip, and p21/Cip, with a decrease in cyclin-D1 expression in hepatocellular carcinoma cells. Novelty and scientific contribution. The current study demonstrates that Tamarix articulata methanolic extract exhibits promising anticancer potential to kill tumor cells by programmed-cell-death type I and II mechanisms and could be explored for potential drug candidate molecules to curtail cancer in the future.

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Esculetin induces cell cycle arrest and apoptosis in human colon cancer LoVo cells

Cited by 25 publications

References 37 publications

Antitumor Effect of the Ethanolic Extract from Seeds of Euphorbia lathyris in Colorectal Cancer

Antitumor Effect of the Ethanolic Extract from Seeds of Euphorbia lathyris in Colorectal Cancer

6,8‐Diprenylorobol induces apoptosis in human colon cancer cells via activation of intracellular reactive oxygen species and p53

Tamarix articulata Inhibits Cell Proliferation, Promotes Cell Death Mechanisms and Triggers G0/G1 Cell Cycle Arrest in Hepatocellular Carcinoma Cells

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