Ferulic Acid Induces Apoptosis of HeLa and Caski Cervical Carcinoma Cells by Down-Regulating the Phosphatidylinositol 3-Kinase (PI3K)/Akt Signaling Pathway

Luo, Liping; Zhu, Sihong; Tong, Yan; Peng, Shiwei

doi:10.12659/msm.920095

Cited by 21 publications

(18 citation statements)

References 37 publications

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“…Similar results, FA can also induce an increase in the expression of Bax, caspase‐3 and caspase‐9 in fibrosarcoma cells (Fahrioglu et al., 2016). The research report of Luo et al also pointed out that FA had cytotoxic effects on HeLa cells and CaSki cervical carcinoma cells (Luo et al., 2020).…”

Section: Discussionmentioning

confidence: 98%

Phytochemical composition and bioactive effects of ethyl acetate fraction extract (EAFE) of Glechoma hederacea L.

Chao

Liou

et al. 2021

J Food Biochem

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Hepatocellular carcinoma (HCC) is a highly malignant cancer that exists worldwide. Herbal medicine plays an important role in the management and treatment of various diseases worldwide. The herbal medicine Glechoma hederacea L. has a variety of biological activities and belongs to the Labiatae family. The current study investigated the in vitro effects of ethyl acetate fraction extract (EAFE) of G. hederacea on HepG2 cells and its possible mechanism. The phytochemical composition of EAFE was analyzed by high performance liquid chromatography (HPLC). Bioactive effects of the EAFE were assessed using the MTT assay, annexin V‐FITC/PI staining, PhiphiLux‐G1D2 kit, DAPI and comet assay, flow cytometry, western blotting. In this study, we found that rosmarinic acid (RA), caffeic acid (CA), and ferulic acid (FA) were the abundant polyphenols in EAFE of G. hederacea. This fraction extract could significantly inhibit HepG2 cell proliferation, make cells apoptosis, and cause S phase arrest. The apoptogenic activity of EAFE involved reactive oxygen species (ROS) induction, Ca2+ accumulation, mitochondrial membrane potential (MMP, ΔΨm) destruction, regulate the Bax/Bcl‐2 ratio and caspases 3, 9 cascade. We propose that the EAFE can inhibit the proliferation of HepG2 cell via intracellular ROS mediated apoptosis. EAFE could be developed as a possible anti‐HCC agent or pharmaceutical industries. Practical applications 1. The rosmarinic acid, caffeic acid, and ferulic acid were the main polyphenolic components in the ethyl acetate fraction extract (EAFE) of Glechoma hederacea. 2. The EAFE treatment exerted cytotoxicity by inducing S arrest and apoptosis in HepG2 cells. 3. Antitumor effect of EAFE through the mitochondria‐mediated pathway and ROS‐mediated ER stress.

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Section: Discussionmentioning

confidence: 98%

Phytochemical composition and bioactive effects of ethyl acetate fraction extract (EAFE) of Glechoma hederacea L.

Chao

Liou

et al. 2021

J Food Biochem

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“…TLR2 augments the intestinal barrier through ZO-1 protein redistribution in response to stress-induced damage under control of the PI3K/AKT pathway (Cario et al, 2007). Several studies suggested that FA inhibits proliferation and induces apoptosis via down-regulating PI3K/AKT signaling pathway dose-dependently and exerts anti-cancer properties in some cancer cells, including 143B and MG63 osteosarcoma cells (30, 100, and 150 mM treatment) (Wang et al, 2016) and Caski human cervical carcinoma cells (4-20 mM treatment) (Luo et al, 2020). FA treatment (10 -30 mM) reverses P-glycoprotein mediated multidrug resistance via inhibition of PI3K/AKT/NF-kB signaling pathway in KB Ch R 8-5 cells (Muthusamy et al, 2019).…”

mentioning

confidence: 99%

Ferulic Acid Ameliorates Lipopolysaccharide-Induced Barrier Dysfunction via MicroRNA-200c-3p-Mediated Activation of PI3K/AKT Pathway in Caco-2 Cells

Guo

Zhao

et al. 2020

Front. Pharmacol.

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Intestinal barrier dysfunction is an important clinical problem in various acute and chronic pathological conditions. Ferulic acid (FA) can attenuate the intestinal epithelial barrier dysfunction, however, the underlying mechanism remains unclear. The present study aimed to uncover the protective effect of FA on intestinal epithelial barrier dysfunction in a Caco-2 cell model of lipopolysaccharide (LPS) stimulation and the underlying mechanism. Caco-2 cells were pretreated with FA and then exposed to LPS stimulation. The barrier function of Caco-2 cells was evaluated by measuring trans-epithelial resistance (TER) and 4-kDa fluorescein isothiocyanate (FITC)-dextran (FD4) flux, and analyzing the tight junction protein expression and structure. The results showed that decreased TER and increased FITC-FD4 flux were observed in Caco-2 cells stimulated with LPS, but these effects were attenuated by FA pretreatment. FA pretreatment inhibited LPS-induced decrease in occludin and ZO-1 mRNA and protein expression. LPS stimulation decreased miR-200c-3p expression, whereas this decrease was inhibited by FA pretreatment. Furthermore, overexpression of miR-200c-3p strengthened the protective effects of FA on LPS-induced Caco-2 cell barrier dysfunction by decreasing epithelial permeability, increasing occludin and ZO-1 protein expression, and maintaining of ZO-1 protein distribution, while suppression of miR-200c-3p reversed the protective effects of FA. LPS treatment increased the expression of PTEN protein and decreased expression of phosphorylated PI3K and AKT proteins. However, pretreatment of FA inhibited expression of PTEN protein and promoted activation of PI3K/AKT signaling pathway in the LPS-treated Caco-2 cells, and this regulatory effect of FA on the PTEN/PI3K/AKT signaling pathway was strengthened or weakened by miR-200c-3p overexpression or suppression, respectively. Our findings suggested that in Caco-2 cells, FA promotes activation of PI3K/AKT pathway by miR-200c-3p-mediated suppression of the negative

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“…FA was shown to accelerate the apoptosis of tumors by regulating heat shock proteins and the PI3K/Akt signaling pathway (Kamm et al, 2019;Luo et al, 2020b). And in ARDS, FA was found to inhibit inflammation and oxidative stress (Zhang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…In melanoma cells, FA was observed to be combined with 2-methoxyestradiol to induce cell death by inhibiting Hsp60 and Hsp90 (Kamm et al, 2019). FA induced the apoptosis of cervical carcinoma cells through the Phosphatidylinositol 3-Kinase (PI3K)/Akt Signaling Pathway (Luo et al, 2020b). However, during lipopolysaccharide-induced acute respiratory distress syndrome, FA, when given beforehand, could depress inflammation and oxidative stress (Zhang et al, 2018).…”

Section: Includingmentioning

confidence: 99%

Ferulic acid regulates miR-17/PTEN axis to inhibit LPS-induced pulmonary microvascular endothelial cells apoptosis through activation of PI3K/Akt pathway

et al. 2022

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Acute lung injury (ALI) is mainly mediated by the damage of pulmonary microvascular endothelial cells (PMVECs). LPS is one of the pathogenic factors leading to microcirculatory abnormalities of ALI. Ferulic acid (FA) exhibits therapeutic effects against various diseases. During lipopolysaccharide-induced acute respiratory distress syndrome, FA, when given beforehand, could depress inflammation and oxidative stress. However, the concrete role and underlying mechanism of FA in ALI have not been well characterized. Ten μg/mL Lipopolysaccharide (LPS) was used to treat rat PMVECs for 24 hr. qRT-PCR was used to detect the level of miR-17 and phosphatase and tensin homolog deleted on chromosome ten (PTEN). Western blot was used to analyze the associated proteins in the PI3K/Akt pathway, and the apoptosis-related proteins. Flow cytometric analysis was performed to detect the apoptosis of PMVECs. MTT assay was constructed to detect the cell viability. Luciferase assay was conducted to detect the target gene of miR-17 and PTEN. A cell model for in vitro studying the role of FA in ALI was established using PMVECs. Our data demonstrate that FA up-regulates miR-17 and declines apoptosis induced by LPS. FA inhibits apoptosis mediated by up-regulating miR-17. Furthermore, we found miR-17 targeted PTEN negatively. FA inhibits cleaved caspase-3 and Bax expression through the PI3K/Akt pathway mediated by up-regulating miR-17. Over-expression of PTEN could contribute to the similar expression trend of the PI3K/Akt signal pathway protein compared to miR-17 inhibitor transfected cells. FA inhibits PMVECs apoptosis induced by LPS via miR-17/PTEN to further regulate the activation of the PI3K/Akt pathway in ALI. We anticipate that our data will provoke additional studies for ALI clinical therapy.

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Ferulic Acid Induces Apoptosis of HeLa and Caski Cervical Carcinoma Cells by Down-Regulating the Phosphatidylinositol 3-Kinase (PI3K)/Akt Signaling Pathway

Cited by 21 publications

References 37 publications

Phytochemical composition and bioactive effects of ethyl acetate fraction extract (EAFE) of Glechoma hederacea L.

Phytochemical composition and bioactive effects of ethyl acetate fraction extract (EAFE) of Glechoma hederacea L.

Ferulic Acid Ameliorates Lipopolysaccharide-Induced Barrier Dysfunction via MicroRNA-200c-3p-Mediated Activation of PI3K/AKT Pathway in Caco-2 Cells

Ferulic acid regulates miR-17/PTEN axis to inhibit LPS-induced pulmonary microvascular endothelial cells apoptosis through activation of PI3K/Akt pathway

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