Rosmarinic acid inhibits proliferation and invasion of hepatocellular carcinoma cells SMMC 7721 via PI3K/AKT/mTOR signal pathway

Wang, Li; Yang, Hua; Wang, Chen; Shi, Xiaoyan; Li, Kunkun

doi:10.1016/j.biopha.2019.109443

Cited by 34 publications

(29 citation statements)

References 24 publications

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“…RA and CA are hydrophilic phenolic compounds, which are common in many well‐known herbs in the Lamiaceae family (Khojasteh et al., 2014). In vitro studies have confirmed that RA can inhibit the proliferation of cancer cells, including lung cancer NCI‐H82 cells, human prostate cancer DU‐145 cells and human chronic myeloid leukemia K‐562 cells (Wang et al., 2019). This molecule RA in combination with Adriamycin has been reported to induce apoptosis by activating mitochondrial‐mediated signalling pathway in HepG2 and Bel‐7402 cells (Huang et al., 2018).…”

Section: Discussionmentioning

confidence: 97%

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: 97%

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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“…Moreover, RA suppressed the PDPK1/Akt/mTOR pathways via LPS-induced neuroinflammation both in vitro and in vivo [109]. Moreover, the invasion and migration of cancer cells were inhibited by RA through the Akt signaling cascade [110][111][112].…”

Section: Discussionmentioning

confidence: 94%

Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways

et al. 2021

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Particulate matter from forest fires (PMFF) is an environmental pollutant causing oxidative stress, inflammation, and cancer cell metastasis due to the presence of polycyclic aromatic hydrocarbons (PAHs). Perilla seed meal contains high levels of polyphenols, including rosmarinic acid (RA). The aim of this study is to determine the anti-oxidative stress, anti-inflammation, and anti-metastasis actions of rosmarinic acid rich fraction (RA-RF) from perilla seed meal and its underlying molecular mechanisms in A549 cells exposed to PMFF. PMFF samples were collected via the air sampler at the University of Phayao, Thailand, and their PAH content were analyzed using GC-MS. Fifteen PAH compounds were detected in PMFF. The PMFF significantly induced intracellular reactive oxygen species (ROS) production, the mRNA expression of pro-inflammatory cytokines, MMP-9 activity, invasion, migration, the overexpression of c-Jun and p-65-NF-κB, and Akt phosphorylation. Additionally, the RA-RF significantly reduced ROS production, IL-6, IL-8, TNF-α, and COX-2. RA-RF could also suppress MMP-9 activity, migration, invasion, and the phosphorylation activity of c-Jun, p-65-NF-κB, and Akt. Our findings revealed that RA-RF has antioxidant, anti-inflammatory, and anti-metastasis properties via c-Jun, p-65-NF-κB, and Akt signaling pathways. RA-RF may be further developed as an inhalation agent for the prevention of lung inflammation and cancer metastasis induced by PM exposure.

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“…Both antioxidant and pro-oxidant activities have been observed at different doses of phenolic compounds [42]. RA has been confirmed to inhibit the proliferation of small cell lung cancer cells (NCI-H82), human prostate cancer cells (DU-145), and human chronic myeloid leukemia cells (K-562) in vitro [43]. Some in vitro studies have shown that RA has certain protective effects against lung cancer, colon cancer, breast cancer, gastric carcinoma, and liver cancer.…”

Section: Hplc Analysis Of the Polyphenol Contents Of Eafe Nbfe And Wfementioning

confidence: 96%

The Antitumor Mechanism of the Polyphenol-enriched Ethyl Acetate Fraction Extract of Glechoma hederacea (Lamiaceae) against HepG2 Cells Involves Apoptosis Pathways

Chao¹,

Liou²,

Ma³

et al. 2020

Preprint

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Background: Glechoma hederacea (Lamiaceae) is a traditional Chinese herb belonging to the Labiatae family and has many biological activities. This study aimed to investigate the in vitro effects of different polar parts of the water extracts of G. hederacea (Lamiaceae) on HepG2 cells and the possible underlying mechanism.Methods: The cytotoxic effects were determined using the MTT assay. Apoptosis was quantified using annexin V-FITC/PI staining. Caspase-3 and caspase-9 activities were measured using PhiphiLux-G1D2 kit. Apoptosis-related protein expression was determined using western blot analysis. Reactive oxygen species (ROS) generation, mitochondrial transmembrane potential (MMP), and calcium ion levels were measured using specific fluorescence probes and flow cytometry. The HepG2 cell antioxidant state was determined using DAPI and comet assay, and antioxidant enzyme activities. The polyphenol contents of different polar parts of fractional extracts were determined using HPLC. Results: Our results showed that rosmarinic acid, caffeic acid, and ferulic acid were the major polyphenolic components in the ethyl acetate fraction extract (EAFE) of G. hederacea L.. EAFE could significantly inhibit HepG2 cell proliferation, induce apoptosis, and cause S phase arrest. The apoptogenic activity of EAFE involved ROS induction, Ca2+ accumulation, glutathione depletion, MMP disruption, caspases 3, 9 activation, and Bax/Bcl-2 ratio increment.Conclusion: Our findings suggest that the polyphenols in the EAFE can inhibit HepG2 cell growth and induce apoptosis through the mitochondria-mediated pathway and ROS-mediated endoplasmic reticulum stress. EAFE could be developed as a functional food or nutraceutical ingredient for chemotherapy.

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Rosmarinic acid inhibits proliferation and invasion of hepatocellular carcinoma cells SMMC 7721 via PI3K/AKT/mTOR signal pathway

Cited by 34 publications

References 24 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.

Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways

The Antitumor Mechanism of the Polyphenol-enriched Ethyl Acetate Fraction Extract of Glechoma hederacea (Lamiaceae) against HepG2 Cells Involves Apoptosis Pathways

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