Cucurbitacin E Inhibits Proliferation and Migration of Intestinal Epithelial Cells via Activating Cofilin

Song, Huapei; Wang, Yu; Li, Li; Sui, Hehuan; Wang, Pei; Wang, Fengjun

doi:10.3389/fphys.2018.01090

Cited by 16 publications

(11 citation statements)

References 38 publications

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“…Damnacanthal, a major component of morinda citrifolia, can inhibit migration and invasion of MDA‐MB‐231 breast carcinoma cells by suppressing phosphorylated cofilin 33 . Cucurbitacin I and E can inhibit kinetic activity of LIMK to phosphorylate cofilin and then retarded proliferation and migration of HeLa cells and Caco‐2 human epithelial colorectal adenocarcinoma 34,35 . Though so many LIMK1 inhibitors exist, few inhibitors act on non‐small cell lung adenocarcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

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Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo

Zhang

Wang

Tian

et al. 2021

J Cellular Molecular Medi

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Lung cancer is the leading cause of cancer‐related deaths. LIM domain kinase (LIMK) 1 is a member of serine/threonine kinase family and highly expressed in various cancers. Luteolin, a polyphenolic plant flavonoid, has been reported to suppress tumour proliferation through inducing apoptosis and autophagy via MAPK activation in glioma. However, the mechanism of luteolin on suppressing lung cancer growth is still unclear. We found that luteolin targeted LIMK1 from the in silico screening and significantly inhibited the LIMK1 kinase activity, which was confirmed with pull‐down binding assay and computational docking models. Treatment with luteolin inhibited lung cancer cells anchorage‐independent colony growth and induced apoptosis and cell cycle arrest at G1 phase. Luteolin also decreased the expression of cyclin D1 and increased the levels of cleaved caspase‐3 by down‐regulating LIMK1 signalling related targets, including p‐LIMK and p‐cofilin. Furthermore, luteolin suppressed the lung cancer patient‐derived xenograft tumour growth by decreasing Ki‐67, p‐LIMK and p‐cofilin expression in vivo. Taken together, these results provide insight into the mechanism that underlies the anticancer effects of luteolin on lung cancer, which involved in down‐regulation of LIMK1 and its interaction with cofilin. It also provides valuable evidence for translation towards lung cancer clinical trials with luteolin.

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Section: Discussionmentioning

confidence: 99%

“…Natural compound, diallyl disulfide from garlic extract also reduced the colorectal cancer cell migration and invasion 35,36 . However, still it needs to expand more animal experiments and pharmacokinetics analysis for applying the cancer patient treatment.…”

Section: Discussionmentioning

confidence: 99%

Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo

Zhang

Wang

Tian

et al. 2021

J Cellular Molecular Medi

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“…These experiments were performed according to previously published methods using β-actin as an internal control (Cao et al, 2013; Song et al, 2018). Briefly, Caco-2 cells were inoculated into six-well culture plates.…”

Section: Methodsmentioning

confidence: 99%

Activation of Cofilin Increases Intestinal Permeability via Depolymerization of F-Actin During Hypoxia in vitro

Song

Zhang

et al. 2019

Front. Physiol.

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Mechanical barriers play a key role in maintaining the normal function of the intestinal mucosa. The barrier function of intestinal epithelial cells is significantly damaged after severe hypoxia. However, the molecular mechanisms underlying this hypoxia-induced damage are still not completely clear. Through the establishment of an in vitro cultured intestinal epithelial cell monolayer model (Caco-2), we treated cells with hypoxia or drugs [jasplakinolide or latrunculin A (LatA)] to detect changes in the transepithelial electrical resistance (TER), the expression of the cellular tight junction (TJ) proteins zonula occludens-1 (ZO-1) and occludin, the distribution of F-actin, the ratio of F-actin/G-actin content, and the expression of the cofilin protein. The results showed that hypoxia and drug treatment could both induce a significant reduction in the TER of the intestinal epithelial cell monolayer and a significant reduction in the expression of the ZO-1 and occludin protein. Hypoxia and LatA could cause a significant reduction in the ratio of F-actin/G-actin content, whereas jasplakinolide caused a significant increase in the ratio of F-actin/G-actin content. After hypoxia, cofilin phosphorylation was decreased. We concluded that the barrier function of the intestinal epithelial cell monolayer was significantly damaged after severe burn injury. The molecular mechanism might be that hypoxia-induced F-actin depolymerization and an imbalance between F-actin and G-actin through cofilin activation resulted in reduced expression and a change in the distribution of cellular TJ proteins.

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“…Similar to our results, other studies have shown that CuE can induce apoptosis in 95D human lung cancer cells, SAS oral squamous cell carcinoma cells, and SW527 breast cancer cells. Furthermore, our previous study showed that CuE could induce G2/M cell cycle arrest in Caco-2 cells ( Song et al, 2018 ). Other studies demonstrate that prolonging the cell cycle may lead to secondary apoptosis ( Liu et al, 2003 ).…”

Section: Discussionmentioning

confidence: 99%

“…CuE has various pharmacological properties, including anti-inflammatory, antitumor, and antioxidant effects ( Attard and Martinoli, 2015 ). Our recent research results showed that CuE inhibits the proliferation and migration of human IECs by activating cofilin, and in hypoxic conditions, activated cofilin regulates the permeability of the intestinal epithelium by depolymerizing F-actin ( Song et al, 2018 , 2019 ). However, the effects of CuE on apoptosis and autophagy in IECs are still unclear and deserve further investigation.…”

Section: Introductionmentioning

confidence: 99%

Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells

et al. 2020

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Apoptosis plays a crucial role in maintaining the structural and functional integrity of the intestinal epithelial barrier. Autophagy mediates injury to and repair of the intestinal epithelial barrier through multiple pathways in pathophysiological conditions. Our earlier study has found that cucurbitacin E (CuE) regulates the proliferation, migration, and permeability of human intestinal epithelial cells (IECs); however, its effects and mechanisms on apoptosis and autophagy are still unclear. This study reported CuE induced apoptosis and promoted autophagy of IECs in a concentration-dependent manner. The results showed that CuE could inhibit the expression of apoptosis-related protein Bcl-2 and drove activation of caspase-3 and cleavage of its substrate poly (ADP-ribose) polymerase. CuE also facilitated the expression of endoplasmic reticulum stress-related proteins, CHOP and Grp78, and autophagy-related proteins, Beclin1 and LC3, while inhibiting the phosphorylation of AKT and mammalian target of rapamycin (mTOR). An autophagy inhibitor, 3-methyladenine, reduced CuE-induced apoptosis. These results suggest that CuE may induce apoptosis and autophagy in IECs via the PI3K/AKT/mTOR signaling pathway and that autophagy following endoplasmic reticulum stress participates in the pro-apoptotic process induced by CuE.

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Cucurbitacin E Inhibits Proliferation and Migration of Intestinal Epithelial Cells via Activating Cofilin

Cited by 16 publications

References 38 publications

Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo

Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo

Activation of Cofilin Increases Intestinal Permeability via Depolymerization of F-Actin During Hypoxia in vitro

Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells

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