DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells

Si, Huaijun; Ba, Gen-Na; Zhuang, Xiangjin; Wang, Jing; Burenbatu, B.; Feng, Qiyu; Wang, Hongyang

doi:10.1371/journal.pone.0231466

Cited by 4 publications

(3 citation statements)

References 30 publications

(34 reference statements)

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“…Some researches revealed that Cos exerted anti-tumor activity by suppressing cell proliferation. One research indicated that Cos prevented the proliferation of liver cancer cells by regulating the signaling pathway of epithelial growth factor (EGF) ( Si et al, 2020 ). Another reported that Cos inhibited the proliferation, invasion, and metastasis of osteosarcoma by inhibiting the STAT3 signaling pathway ( Jin et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer

Huang

Lei

et al. 2021

Front. Cell Dev. Biol.

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Objective: Costunolide (Cos) is a sesquiterpene lactone extracted from chicory. Although it possesses anti-tumor effects, the underlying molecular mechanism against gastric cancer cells remains unclear. This study aimed to explore the effect and potential mechanism of Cos on gastric cancer.Methods: The effect of Cos on HGC-27 and SNU-1 proliferation was detected by CCK-8 and clone formation assay. The changes in cell apoptosis were determined using Hoechst 33258 and tunel staining. The morphology of autophagy was analyzed by autophagosomes with the electron microscope and LC3-immunofluorescence with the confocal microscope. The related protein levels of the cell cycle, apoptosis, autophagy and AKT/GSK3β pathway were determined by Western blot. The anti-tumor activity of Cos was evaluated by subcutaneously xenotransplanting HGC-27 into Balb/c nude mice. The Ki67 and P-AKT levels were examined by immunohistochemistry.Results: Cos significantly inhibited HGC-27 and SNU-1 growth and induced cell cycle arrest in the G2/M phase. Cos activated intrinsic apoptosis and autophagy through promoting cellular reactive oxygen species (ROS) levels and inhibiting the ROS-AKT/GSK3β signaling pathway. Moreover, preincubating gastric carcinoma cells with 3-methyladenine (3-MA), a cell-autophagy inhibitor, significantly alleviated the effects of Cos in inducing cell apoptosis.Conclusion: Cos induced apoptosis of gastric carcinoma cells via promoting ROS and inhibiting AKT/GSK3β pathway and activating pro-death cell autophagy, which may be an effective strategy to treat gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer

Huang

Lei

et al. 2021

Front. Cell Dev. Biol.

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“…89 A traditional herbal remedy, known as DaHuangWan, constituted of BBR and costunolide, suppresses the proliferation of hepatoma cells through modulating the epithelial growth factor (EGF) mechanism. 119 Moreover, BBR can hamper cell proliferation of HepG2, Hep3B, and SNU-182 via promoting protein expression of tumor suppressor genes, like activating transcription factor 3 (ATF3). 92…”

Section: Mechanistic Effects Of Bbr On Liver Cancermentioning

confidence: 99%

Effects of Berberine on Liver Cancer

Liu

Nwafor

Wang

et al. 2022

Natural Product Communications

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Liver cancer, otherwise known as hepatocellular carcinoma, is a chronic disease condition with an excessive deposition and growth of malignant cells in the body. The high incidence and prevalence rates of liver cancer continue to be problems, as well as its poor prognosis and therapeutic limitations involving severe drug adverse reactions linked to the use of synthetic chemotherapeutic compounds. Continuous experimental studies, as well as utilization of pure herbal-based compounds, are essential towards finding more potent cures for liver cancer. Natural bioactive compounds, particularly alkaloids (eg, berberine), have been shown to be highly beneficial in the treatment of various diseases. Berberine (BBR), an isoquinoline alkaloid, is obtained from stem, bark, roots, rhizomes, and leaves of several medicinal plants, including Berberis species. It is commonly synthesized from the benzyltetrahydroisoquinoline system with the incorporation of an additional carbon atom as a bridge. The multiple attributes of BBR involving effective inhibitory and cytotoxic actions against the proliferation of cancer cells have been demonstrated. The use of BBR in experimental studies (in vivo and in vitro) for over a decade for liver cancer treatment has proven to be highly effective, safe, and potent. Until now, the poor solubility of BBR remains one of the contributing factors leading to its minimal clinical bioavailability. Therefore, BBR could serve as a prospective drug candidate in the future towards drug formulation for liver cancer treatment. The relevant information regarding this review was obtained electronically through the use of databases such as PubMed, Google Scholar, Springer, Hindawi, Embase, Web of Science, and China National Knowledge Infrastructure. All the aforementioned databases were searched from 1981 to 2020. This literature represents an update of previous review papers discussing the various positive pharmacological and mechanistic effects (oxidative stress regulation, inflammation reduction, apoptosis activation, overcoming drug resistance, and metastasis inhibition) of BBR for liver cancer treatment, which would be of great significance to drug development and clinical research.

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“…Additionally, the addition of delphinidin (a flavonoid) [ 58 ] and ginsenoside Rg3 [ 59 ] to the culture medium inhibited the EGFR/Akt/ERK signal axis in liver cancer cells. Da Huang Wan, a traditional herbal medicine, also decreased tumor progression in vitro by modulating EGF [ 60 ]. These results indicate that both HGF and EGF might exert their effects via the same signaling pathways i.e., Akt/ERK.…”

Section: Growth Factors In Liver Tumorigenesis and Liver Regenerationmentioning

confidence: 99%

Insights into Growth Factors in Liver Carcinogenesis and Regeneration: An Ongoing Debate on Minimizing Cancer Recurrence after Liver Resection

et al. 2021

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Hepatocellular carcinoma has become a leading cause of cancer-associated mortality throughout the world, and is of great concern. Currently used chemotherapeutic drugs in the treatment of hepatocellular carcinoma lead to severe side effects, thus underscoring the need for further research to develop novel and safer therapies. Liver resection in cancer patients is routinely performed. After partial resection, liver regeneration is a perfectly calibrated response apparently sensed by the body’s required liver function. This process hinges on the effect of several growth factors, among other molecules. However, dysregulation of growth factor signals also leads to growth signaling autonomy and tumor progression, so control of growth factor expression may prevent tumor progression. This review describes the role of some of the main growth factors whose dysregulation promotes liver tumor progression, and are also key in regenerating the remaining liver following resection. We herein summarize and discuss studies focused on partial hepatectomy and liver carcinogenesis, referring to hepatocyte growth factor, insulin-like growth factor, and epidermal growth factor, as well as their suitability as targets in the treatment of hepatocellular carcinoma. Finally, and given that drugs remain one of the mainstay treatment options in liver carcinogenesis, we have reviewed the current pharmacological approaches approved for clinical use or research targeting these factors.

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DaHuangWan targets EGF signaling to inhibit the proliferation of hepatoma cells

Cited by 4 publications

References 30 publications

Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer

Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer

Effects of Berberine on Liver Cancer

Insights into Growth Factors in Liver Carcinogenesis and Regeneration: An Ongoing Debate on Minimizing Cancer Recurrence after Liver Resection

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