Berberine inhibits EGFR signaling and enhances the antitumor effects of EGFR inhibitors in gastric cancer

Wang, Junxiong; Yang, Shuo; Cai, Xiqiang; Dong, Jiaqiang; Chen, Zhangqian; Wang, Rui; Zhang, Song; Cao, Haichao; Lü, Di; Jin, Tao; Nie, Yongzhan; Hao, Jianyu; Fan, Daiming

doi:10.18632/oncotarget.12589

Cited by 62 publications

(50 citation statements)

References 30 publications

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“…In addition, berberine modulated the sensitivity of cisplatin through the miR-93/PTEN/AKT signaling pathway in ovarian cancer cells (32) and attenuated the antitumor activity of 5-FU, camptothecin and paclitaxel (33). Berberine was also found to sensitize cancer cells to PARP and epidermal growth factor receptor inhibitors (18,34). In the present study, berberine and sorafenib were found to exert anti-proliferative effects on HCC cells in a dose-and time-dependent manner.…”

Section: Discussionsupporting

confidence: 53%

“…It is traditionally used as an antibiotic to treat Berberine, a natural plant alkaloid, synergistically sensitizes human liver cancer cells to sorafenib dysentery, gastrointestinal diseases and diarrhea in China, and is a relatively cheap compound (14,15). Previous studies have reported that berberine exerts an anticancer activity in multiple types of cancer and inhibits the proliferation of cancer cells by inducing apoptosis (16)(17)(18)(19). The possible molecular mechanism of the effect of berberine involves its interaction with numerous molecular targets, including transcription factors, cytokines, enzymes, receptors, oncomiRs and tumor-suppressive miRs (20).…”

Section: Introductionmentioning

confidence: 99%

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Berberine, a natural plant alkaloid, synergistically sensitizes human liver cancer cells to sorafenib

Huang

Wang

et al. 2018

Oncol Rep

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Sorafenib resistance is one of the major factors affecting the prognosis of patients with hepatocellular carcinoma (HCC). Increasing evidence has indicated that certain traditional medicines can enhance the sensitivity of cancer cells to sorafenib. Berberine, an isoquinoline alkaloid, has been demonstrated to possess antitumor properties against various malignancies. However, the synergistic effect of the combination of berberine and sorafenib in HCC remains unknown. The aim of the present study was to determine the effects of berberine and sorafenib combination on the growth of liver cancer cells. Initially, it was observed that the combination of sorafenib and berberine exerted a synergistic inhibitory effect on the proliferation of SMMC‑7721 and HepG2 cells in a dose‑ and time‑dependent manner by an MTS assay. Edu staining and colony formation assays also revealed that the combination of 100 µM berberine and 4 µM sorafenib exhibited a significant anti‑proliferation effect on SMMC‑7721 and HepG2 cells. Furthermore, western blotting assay indicated that the expressions levels of cleaved poly(ADP‑ribose) polymerase and cleaved caspase‑3 increased, while those of the anti‑apoptotic protein B‑cell lymphoma 2 and vascular endothelial growth factor decreased. To the best of our knowledge, this is the first study to demonstrate that berberine sensitized liver cancer cells to sorafenib treatment. These results suggest that berberine combined with sorafenib is able to inhibit the proliferation of liver cancer cells and induce apoptosis, which provides evidence for further clinical investigation in HCC patients with sorafenib resistance.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Berberine, a natural plant alkaloid, synergistically sensitizes human liver cancer cells to sorafenib

Huang

Wang

et al. 2018

Oncol Rep

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“…TCM has gained increasing attention because of its role in cancer prevention and treatment [38-40]. Huaier extract has been used in China for approximately 1600 years [4]; however, its anti-tumor effects were confirmed more recently [8, 13, 41].…”

Section: Discussionmentioning

confidence: 99%

Huaier Extract Inhibits Breast Cancer Progression Through a LncRNA-H19/MiR-675-5p Pathway

Wang

Chen

et al. 2017

Cell Physiol Biochem

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Background/Aims: Increasing evidence indicates that Huaier extract has promising therapeutic effects against cancer. However, the mechanisms that underlie its anti-tumor effects remain unclear. In recent years, various studies have shown that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cancer development and progression. Here, we explored the role of lncRNAs in Huaier-induced tumor suppression. Methods: Microarray profiling was performed to identify the candidate lncRNAs affected by Huaier extract. Quantitative realtime PCR (qPCR) was used to evaluate the transfection efficiency and the influence of Huaier extract on H19 expression. The effect of Huaier extract on the cell viability was examined by MTT. Moreover, the rates of apoptotic cells were detected using flow-cytometric analysis. Western blot analysis was applied to show the protein levels of CBL. Results: Microarray data derived from Huaier-treated breast cancer cells identified H19 as a potential target. Huaier extract reduced the expression of H19. The over-expression of H19 inhibited the cytotoxic effects of Huaier extract; in contrast, reduced H19 expression enhanced the function of Huaier extract. MiR-675-5p was identified as a mature product of H19. Moreover, Huaier extract reduced the miR-675-5p expression. Upregulating miR-675-5p reversed the inhibitory effects of Huaier extract, whereas downregulating miR-675-5p sensitized breast cancer cells to the effect of Huaier extract. In addition, Huaier extract increased the expression of CBL protein, a direct target of miR-675-5p. Conclusion: Collectively, the data demonstrate that Huaier extract reduces viability and induces apoptosis in breast cancer cells via H19-miR-675-5p-CBL axis regulation.

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“…Our previous study proved that berberine could attenuate the proliferation and induce cell cycle arrest of gastric cancer cell lines by targeting the AMPK/ HNF4α/WNT5a pathway [15]. It was also confirmed that berberine inhibited the growth and induced apoptosis of gastric cancer cell lines, which effects were linked to inhibition of EGFR signals [14]. However, whether berberine exerted growth inhibition effects against tumors through regulating the lipid metabolism remained to be elucidated.…”

Section: Introductionmentioning

confidence: 90%

“…Berberine, extracted from Chinese herbs such as Coptis, is traditionally used to treat gastrointestinal infections such as bacterial diarrhea in China for a long time. Recent investigations have discovered its properties against many diseases including obesity, hypolipidemia [13], and gastric cancers [14]. Our previous study proved that berberine could attenuate the proliferation and induce cell cycle arrest of gastric cancer cell lines by targeting the AMPK/ HNF4α/WNT5a pathway [15].…”

Section: Introductionmentioning

confidence: 98%

Berberine Suppressed Tumor Growth through Regulating Fatty Acid Metabolism and Triggering Cell Apoptosis via Targeting FABPs

Peng

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Aim. To further investigate the mechanism behind the antitumor properties of berberine regarding lipid metabolism. Methods. Cell viability, proliferation, and apoptosis assays were performed to determine the antigrowth effects of berberine in vitro. Ectopic xenograft models in Balb/c nude mice were established to determine the antitumor effects of berberine in vivo. Results. Berberine inhibited cell viability and proliferation of MGC803 human gastric cancer cell lines in a time-and dose-dependent manner. Berberine induced apoptosis of MGC803 and increased the apoptotic rate with higher doses. Berberine induced the accumulation of fatty acid of MGC803 and suppressed the protein expression of FABPs and PPARα. e FABP inhibitor BMS309403 recapitulated the effects of berberine on MGC803 cells. In the xenograft model, berberine significantly decreased the tumor volume and tumor weight and induced apoptosis in tumor tissues. Berberine significantly elevated the fatty acid content and inhibited the expression of FABPs and PPARα in the MGC803 xenograft models. Conclusion. Berberine exerted anticancer effects on human gastric cancer both in vitro and in vivo by inducing apoptosis, which was due to the reduced protein expression of FABPs and the accumulation of fatty acid.

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Berberine inhibits EGFR signaling and enhances the antitumor effects of EGFR inhibitors in gastric cancer

Cited by 62 publications

References 30 publications

Berberine, a natural plant alkaloid, synergistically sensitizes human liver cancer cells to sorafenib

Berberine, a natural plant alkaloid, synergistically sensitizes human liver cancer cells to sorafenib

Huaier Extract Inhibits Breast Cancer Progression Through a LncRNA-H19/MiR-675-5p Pathway

Berberine Suppressed Tumor Growth through Regulating Fatty Acid Metabolism and Triggering Cell Apoptosis via Targeting FABPs

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