Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastric Cancer Cell Biological Activity and Its Mechanism

Yan, Yi–Dan; Mao, Guoxin

doi:10.12659/msm.923962

Cited by 3 publications

(3 citation statements)

References 36 publications

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“…In fact, some of the predicted herbs such as Rhizoma Coptidis (Chai et al, 2018;Kim et al, 2019), Rhizoma Polygoni cuspidati (Jiang et al, 2017) and Radix Salviae liguliobae (Wilke et al, 2014) have been shown to have significant anti-gastric cancer effects. Predicted anti-gastric cancer effects of herbal ingredients such as taxol (Huang et al, 2020b;Zhang et al, 2021), coumarin (Kaur et al, 2015;Xu et al, 2017), resveratrol (Yan et al, 2020;Ren et al, 2021) and magnolol (Zhao et al, 2022) have also been demonstrated. Among the molecular docking results of these herbal ingredients with key genes, we found that TLR4 could bind closely to salvianolic acid b (−7.6 kcal/mol), and shikonin (−6.9 kcal/mol), while KRAS bound closely to coumarin (−6.7 kcal/mol) and magnolol (−6.9 kcal/mol).…”

Section: Discussionmentioning

confidence: 97%

Development of alternative herbals remedy for gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis

Tao²,

Qian³

et al. 2023

Front. Genet.

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Objective: Screening out potential herbal medicines and herbal ingredients for the treatment of gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis.Methods: Gene expression profiles of gastric tumour tissues and normal tissue samples were obtained from the GEO database and the samples were analysed for immune cell infiltration condition and differential expressed genes of ferroptosis. Key genes were screened by protein-protein interaction (PPI) and enrichment analysis, and molecular docking was used to predict and preliminary validate potential herbal and traditional Chinese medicine components for gastric cancer based on the key genes. Finally, RT-QPCR was used to validate the prediction results.Results: Immune cell infiltration analysis revealed high levels of infiltration of activated CD4 memory T cells, monocytes, M0 macrophages in gastric tumor tissues, while plasma cells and resting mast cells had higher levels of infiltration in the paraneoplastic tissues. Differential gene expression analysis identified 1,012 upregulated genes and 880 downregulated genes, of which 84 immune related differentially expressed genes such as CTSB, PGF and PLAU and 10 ferroptosis-related differentially expressed genes such as HSF1, NOX4 and NF2 were highly expressed in gastric cancer tissues. The results of enrichment analysis showed that they mainly involve 343 biological processes such as extracellular matrix organization and extracellular structural organization; 37 cellular components such as complexes of collagen trimer and basement membrane; 35 molecular functions such as signal receptor activator activity and receptor ligand activity; 19 regulatory pathways such as cytokine-cytokine receptor interactions and retinol metabolism. Finally, two key genes, TLR4 and KRAS, were selected and 12 herbal medicines such as Radix Salviae liguliobae, Rhizoma Coptidis, Rhizoma Polygoni cuspidati and 27 herbal ingredients such as resveratrol, salvianolic acid b were predicted on the basis of key genes. Molecular docking results showed that KRAS binds tightly to coumarin and magnolol, while TLR4 can bind tightly to resveratrol, curcumin, salvianolic acid b, shikonin. Subsequently, the effect of resveratrol and magnolol was experimentally verified.Conclusion: Herbal medicines such as S. liguliobae, Rhizoma Coptidis, Rhizoma P. cuspidati and herbal ingredients such as resveratrol, curcumin, salvianolic acid b may provide research directions and alternative therapeutic approaches for immunomodulation of TME and ferroptosis of tumour cells in gastric cancer.

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Section: Discussionmentioning

confidence: 97%

Development of alternative herbals remedy for gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis

Tao²,

Qian³

et al. 2023

Front. Genet.

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“…In addition, HNK can interfere with the crosstalk between cancer cells and stromal cells, and this effect is achieved by inhibiting the expression of CXCR4 and SHH, thereby suppressing pancreatic cancer growth and metastasis ( 14 ). HNK can also inhibit EMT, migration, invasion, and angiogenesis in various cancers, including breast cancer ( 15 ), bladder cancer ( 16 ), lung cancer ( 17 ), and gastric cancer ( 18 , 19 ). In addition, HNK can alleviate scale hyperplasia by inhibiting the phosphorylation of SMAD2/3 but does not inhibit the expression of TGF β ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling

Qin

Xiao

et al. 2021

Front. Oncol.

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BackgroundPerineural invasion (PNI) is an important pathologic feature of pancreatic cancer, and the incidence of PNI in pancreatic cancer is 70%-100%. PNI is associated with poor outcome, metastasis, and recurrence in pancreatic cancer patients. There are very few treatments for PNI in pancreatic cancer. Honokiol (HNK) is a natural product that is mainly obtained from Magnolia species and has been indicated to have anticancer activity. HNK also has potent neurotrophic activity and may be effective for suppressing PNI. However, the potential role of HNK in the treatment of PNI in pancreatic cancer has not been elucidated.MethodsIn our study, pancreatic cancer cells were treated with vehicle or HNK, and the invasion and migration capacities were assessed by wound scratch assays and Transwell assays. A cancer cell-dorsal root ganglion coculture model was established to evaluate the effect of HNK on the PNI of pancreatic cancer. Western blotting was used to detect markers of EMT and neurotrophic factors in pancreatic tissue. Recombinant TGF-β1 was used to activate SMAD2/3 to verify the effect of HNK on SMAD2/3 and neurotrophic factors. The subcutaneous tumor model and the sciatic nerve invasion model, which were established in transgenic engineered mice harboring spontaneous pancreatic cancer, were used to investigate the mechanism by which HNK inhibits EMT and PNI in vivo.ResultsWe found that HNK can inhibit the invasion and migration of pancreatic cancer cells. More importantly, HNK can inhibit the PNI of pancreatic cancer. The HNK-mediated suppression of pancreatic cancer PNI was partially mediated by inhibition of SMAD2/3 phosphorylation. In addition, the inhibitory effect of HNK on PNI can be reversed by activating SMAD2/3. In vivo, we found that HNK can suppress EMT in pancreatic cancer. HNK can also inhibit cancer cell migration along the nerve, reduce the damage to the sciatic nerve caused by tumor cells and protect the function of the sciatic nerve.ConclusionOur results demonstrate that HNK can inhibit the invasion, migration, and PNI of pancreatic cancer by blocking SMAD2/3 phosphorylation, and we conclude that HNK may be a new strategy for suppressing PNI in pancreatic cancer.

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“…Honokiol is a biologically active ingredient isolated from the Chinese herbal medicine magnolia, which can effectively inhibit the growth of tumor cells. According to the literature, honokiol can induce apoptosis in pancreatic and gastric cancer cells ( 4 , 5 ), and can also inhibit the growth and metastasis of melanoma ( 6 ). Current breast cancer research is limited to the effects of honokiol on the two human epidermal growth factor receptor 2 (HER2)-negative cell lines MDA-MB-231 and MCF-7 ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Honokiol inhibits the growth of SKBR3 cells

Shi¹,

Wang²,

Yao³

et al. 2020

Transl Cancer Res TCR

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Background: Breast cancer is one of the most malignant tumors in the reproductive system and has a poor prognosis. Finding drugs with high efficiency, low side-effects, and low cost has become a research hotspot.Methods: In the present study, we treated SK-BR-3 cells with different doses of honokiol. Crystal violet staining method was used to detect changes in the total number of living cells; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to detect the effect of honokiol on SK-BR-3 cell proliferation. Cell migration ability change was determined by wound healing assay. Cell invasion ability change was determined by Transwell migration assay. Flow cytometry was used to detect the apoptotic rate of SK-BR-3 cells, and Western blot was used to detect the expression levels of proliferation-associated protein (PCNA); migration-and invasion-related protein matrix metalloproteinase-2 (MMP-2); vimentin; apoptosis-related proteins Bcl-xl, caspase 3, and cleaved caspase 3 (CC3); and β-catenin and its downstream target molecule c-Myc. Results: Compared with the control group, different doses of honokiol have different degrees of inhibitory effects on cells, including proliferation and invasion and migration (P<0.01). After treatment with 50 or 60 μmol•L -1 honokiol, the apoptotic rate of SK-BR-3 cells increased (both P<0.01); PCNA expression was significantly downregulated (P<0.01). Intracellular accumulation of apoptosis-related proteins Bcl-xl and caspase-3 decreased but C-C3 increased. We also found downregulation of MMP-2 expression, a protein related to invasion and migration (P<0.01), and a decrease in the expression levels of the Wnt/β-catenin signaling pathway-related proteins β-catenin and c-Myc (P<0.01). Conclusions: Honokiol can promote the apoptosis of SK-BR-3 cells and can inhibit the proliferation, migration, and invasion of human breast cancer SK-BR-3 cells. The underlying mechanism may be through inhibiting the activation of the Wnt signaling pathway.

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Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastric Cancer Cell Biological Activity and Its Mechanism

Cited by 3 publications

References 36 publications

Development of alternative herbals remedy for gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis

Development of alternative herbals remedy for gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis

Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling

Honokiol inhibits the growth of SKBR3 cells

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