Zingerone suppresses proliferation, invasion, and migration of hepatocellular carcinoma cells by the inhibition of MTDH-mediated PI3K/Akt pathway

References

• Hartke J, Johnson M, Ghabril M. The diagnosis and treatment of hepatocellular carcinoma. Semin Diagn Pathol. 2017;34(2):153–159.
   PubMed Web of Science ®Google Scholar
• Lee SS, Shin HS, Kim HJ, et al. Analysis of prognostic factors and 5-year survival rate in patients with hepatocellular carcinoma: a single-center experience. Korean J Hepatol. 2012;18(1):48–55.
   PubMedGoogle Scholar
• Xiang Y, Guo Z, Zhu P, et al. Traditional Chinese medicine as a cancer treatment: modern perspectives of ancient but advanced science. Cancer Med. 2019;8(5):1958–1975.
   PubMed Web of Science ®Google Scholar
• Hsiao WL, Liu L. The role of traditional Chinese herbal medicines in cancer therapy-from TCM theory to mechanistic insights. Planta Med. 2010;76(11):1118–1131.
   PubMed Web of Science ®Google Scholar
• Hoffman RD, Li CY, He K, et al. Chinese herbal medicine and its regulatory effects on tumor related T cells. Front Pharmacol. 2020;11:492.
   PubMed Web of Science ®Google Scholar
• Mahomoodally MF, Aumeeruddy MZ, Rengasamy KRR, et al. Ginger and its active compounds in cancer therapy: from folk uses to nano-therapeutic applications. Semin Cancer Biol. 2021;69:140–149.
   PubMed Web of Science ®Google Scholar
• Soliman AF, Anees LM, Ibrahim DM. Cardioprotective effect of zingerone against oxidative stress, inflammation, and apoptosis induced by cisplatin or gamma radiation in rats. Naunyn Schmiedebergs Arch Pharmacol. 2018;391(8):819–832.
   PubMed Web of Science ®Google Scholar
• Lee W, Ku SK, Kim MA, et al. Anti-factor Xa activities of zingerone with anti-platelet aggregation activity. Food Chem Toxicol. 2017;105:186–193.
   PubMed Web of Science ®Google Scholar
• Gungor H, Ekici M, Onder Karayigit M, et al. Zingerone ameliorates oxidative stress and inflammation in bleomycin-induced pulmonary fibrosis: modulation of the expression of TGF-β1 and iNOS. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(9):1659–1670.
   PubMed Web of Science ®Google Scholar
• Gan H, Zhang Y, Zhou Q, et al. Zingerone induced caspase-dependent apoptosis in MCF-7 cells and prevents 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in experimental rats. J Biochem Mol Toxicol. 2019;33(10):e22387.
   PubMed Web of Science ®Google Scholar
• Lechner JF, Stoner GD. Gingers and their purified components as cancer chemopreventative agents. Molecules. 2019;24(16):2859.
   Web of Science ®Google Scholar
• Kim YJ, Jeon Y, Kim T, et al. Combined treatment with zingerone and its novel derivative synergistically inhibits TGF-β1 induced epithelial-mesenchymal transition, migration and invasion of human hepatocellular carcinoma cells. Bioorg Med Chem Lett. 2017;27(4):1081–1088.
   PubMed Web of Science ®Google Scholar
• Kung ML, Lin PY, Huang ST, et al. Zingerone nanotetramer strengthened the polypharmacological efficacy of zingerone on human hepatoma cell lines. ACS Appl Mater Interfaces. 2019;11(1):137–150.
   PubMed Web of Science ®Google Scholar
• Wang Z, Tang ZY, Yin Z, et al. Metadherin regulates epithelial-mesenchymal transition in carcinoma. Onco Targets Ther. 2016;9:2429–2436.
   PubMed Web of Science ®Google Scholar
• Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2(6):442–454.
   PubMed Web of Science ®Google Scholar
• Emdad L, Das SK, Dasgupta S, et al. AEG-1/MTDH/LYRIC: signaling pathways, downstream genes, interacting proteins, and regulation of tumor angiogenesis. Adv Cancer Res. 2013;120:75–111.
   PubMed Web of Science ®Google Scholar
• Zhu K, Dai Z, Pan Q, et al. Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res. 2011;17(23):7294–7302.
   PubMed Web of Science ®Google Scholar
• Li C, Wu X, Zhang W, et al. High-content functional screening of AEG-1 and AKR1C2 for the promotion of metastasis in liver cancer. J Biomol Screen. 2016;21(1):101–107.
   PubMedGoogle Scholar
• Zhu K, Peng Y, Hu J, et al. Metadherin-PRMT5 complex enhances the metastasis of hepatocellular carcinoma through the WNT-β-catenin signaling pathway. Carcinogenesis. 2020;41(2):130–138.
   PubMed Web of Science ®Google Scholar
• Sarkar D. AEG-1/MTDH/LYRIC in liver cancer. Adv Cancer Res. 2013;120:193–221.
   PubMed Web of Science ®Google Scholar
• Song YH, Jeong SJ, Kwon HY, et al. Ursolic acid from oldenlandia diffusa induces apoptosis via activation of caspases and phosphorylation of glycogen synthase kinase 3 beta in SK-OV-3 ovarian cancer cells. Biol Pharm Bull. 2012;35(7):1022–1028.
   PubMed Web of Science ®Google Scholar
• Luo Z, Hu X, Xiong H, et al. A polysaccharide from huaier induced apoptosis in MCF-7 breast cancer cells via down-regulation of MTDH protein. Carbohydr Polym. 2016;151:1027–1033.
   PubMed Web of Science ®Google Scholar
• Bi J, Areecheewakul S, Li Y, et al. MTDH/AEG-1 downregulation using pristimerin-loaded nanoparticles inhibits fanconi anemia proteins and increases sensitivity to platinum-based chemotherapy. Gynecol Oncol. 2019;155(2):349–358.
   PubMed Web of Science ®Google Scholar
• Sun Y, Wang W, Tong Y. Berberine inhibits proliferative ability of breast cancer cells by reducing metadherin. Med Sci Monit. 2019;25:9058–9066.
   PubMed Web of Science ®Google Scholar
• Fischer N, Seo EJ, Efferth T. Prevention from radiation damage by natural products. Phytomedicine. 2018;47:192–200.
   PubMed Web of Science ®Google Scholar
• Shi X, Wang X. The role of MTDH/AEG-1 in the progression of cancer. Int J Clin Exp Med. 2015;8(4):4795–4807.
   PubMed Web of Science ®Google Scholar
• Zhou Q, Lui VW, Yeo W. Targeting the PI3K/akt/mTOR pathway in hepatocellular carcinoma. Future Oncol. 2011;7(10):1149–1167.
   PubMed Web of Science ®Google Scholar
• Ding ZY, Dong G, Yin G, et al. Knockdown of metadherin suppressed the progression of oral squamous cell carcinoma via PI3K/AKT signaling pathway. J Biol Regul Homeost Agents. 2021;35(1):303–309.
   PubMed Web of Science ®Google Scholar
• Porta-Sánchez A, Gilbert C, Spears D, et al. Incidence, diagnosis, and management of QT prolongation induced by cancer therapies: a systematic review. J Am Heart Assoc. 2017;6(12):e007724.
   PubMed Web of Science ®Google Scholar
• de Lima RMT, Dos Reis AC, de Menezes APM, et al. Protective and therapeutic potential of ginger (zingiber officinale) extract and [6]-gingerol in cancer: a comprehensive review. Phytother Res. 2018;32(10):1885–1907.
   PubMed Web of Science ®Google Scholar
• Choi JS, Ryu J, Bae WY, et al. Zingerone suppresses tumor development through decreasing cyclin D1 expression and inducing mitotic arrest. Int J Mol Sci. 2018;19(9):2832.
   Web of Science ®Google Scholar
• Bae WY, Choi JS, Kim JE, et al. Zingerone suppresses angiogenesis via inhibition of matrix metalloproteinases during tumor development. Oncotarget. 2016;7(30):47232–47241.
   PubMedGoogle Scholar
• Qian S, Fang H, Zheng L, et al. Zingerone suppresses cell proliferation via inducing cellular apoptosis and inhibition of the PI3K/AKT/mTOR signaling pathway in human prostate cancer PC-3 cells. J Biochem Mol Toxicol. 2021;35(1):e22611.
   PubMed Web of Science ®Google Scholar
• Radhakrishnan EK, Bava SV, Narayanan SS, et al. [6]-gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in Colon cancer cells by inhibiting MAPK/AP-1 signaling. PLoS One. 2014;9(8):e104401.
   PubMed Web of Science ®Google Scholar
• Hu SM, Yao XH, Hao YH, et al. 8‑Gingerol regulates colorectal cancer cell proliferation and migration through the EGFR/STAT/ERK pathway. Int J Oncol. 2020;56(1):390–397.
   PubMed Web of Science ®Google Scholar
• Baptista Moreno Martin AC, Tomasin R, Luna-Dulcey L, et al. [10]-gingerol improves doxorubicin anticancer activity and decreases its side effects in triple negative breast cancer models. Cell Oncol. 2020;43(5):915–929.
   Web of Science ®Google Scholar
• Luo Y, Chen X, Luo L, et al. [6]-gingerol enhances the radiosensitivity of gastric cancer via G2/M phase arrest and apoptosis induction. Oncol Rep. 2018;39:2252–2260.
   PubMed Web of Science ®Google Scholar
• Li JW, Huang CZ, Li JH, et al. Knockdown of metadherin inhibits cell proliferation and migration in colorectal cancer. Oncol Rep. 2018;40:2215–2223.
   PubMed Web of Science ®Google Scholar
• Feng D, Yu X, Tian X, et al. Metadherin promotes malignant phenotypes and induces Beta-Catenin nuclear translocation and Epithelial-Mesenchymal transition in gastric cancer. Cancer Manag Res. 2019;11:8911–8921.
   PubMed Web of Science ®Google Scholar
• Zhou J, Li J, Wang Z, et al. Metadherin is a novel prognostic marker for bladder cancer progression and overall patient survival. Asia Pac J Clin Oncol. 2012;8(3):e42–e48.
   PubMed Web of Science ®Google Scholar
• Ding Z, Zhang Z, Jin X, et al. Interaction with AEG-1 and MDM2 is associated with glioma development and progression and correlates with poor prognosis. Cell Cycle. 2019;18(2):143–155.
   PubMed Web of Science ®Google Scholar
• Yu C, Liu Y, Tan H, et al. Metadherin regulates metastasis of squamous cell carcinoma of the head and neck via AKT signalling pathway-mediated epithelial-mesenchymal transition. Cancer Lett. 2014;343(2):258–267.
   PubMed Web of Science ®Google Scholar
• El-Ashmawy NE, El-Zamarany EA, Khedr EG, et al. Activation of EMT in colorectal cancer by MTDH/NF-κB p65 pathway. Mol Cell Biochem. 2019;457(1–2):83–91.
   PubMed Web of Science ®Google Scholar
• Li PP, Feng LL, Chen N, et al. Metadherin contributes to the pathogenesis of chronic lymphocytic leukemia partially through wnt/β-catenin pathway. Med Oncol. 2015;32(2):479.
   PubMed Web of Science ®Google Scholar
• Xi J, Feng J, Li Q, et al. The long non-coding RNA lncFOXO1 suppresses growth of human breast cancer cells through association with BAP1. Int J Oncol. 2017;50(5):1663–1670.
   PubMed Web of Science ®Google Scholar
• Chen Y, Wu H, Wang X, et al. Huaier granule extract inhibit the proliferation and metastasis of lung cancer cells through down-regulation of MTDH, JAK2/STAT3 and MAPK signaling pathways. Biomed Pharmacother. 2018;101:311–321.
   PubMed Web of Science ®Google Scholar
• Yang C, Zheng S, Liu T, et al. Down-regulated miR-26a promotes proliferation, migration, and invasion via negative regulation of MTDH in esophageal squamous cell carcinoma. FASEB J. 2017;31(5):2114–2122.
   PubMed Web of Science ®Google Scholar
• Chen F, Wang S, Wei Y, et al. Norcantharidin modulates the miR-30a/metadherin/AKT signaling axis to suppress proliferation and metastasis of stromal tumor cells in giant cell tumor of bone. Biomed Pharmacother. 2018;103:1092–1100.
   PubMed Web of Science ®Google Scholar
• Zhang L, Li C, Cao L, et al. microRNA-877 inhibits malignant progression of colorectal cancer by directly targeting MTDH and regulating the PTEN/akt pathway. Cancer Manag Res. 2019;11:2769–2781.
   PubMed Web of Science ®Google Scholar