SMYD3-associated pathway is involved in the anti-tumor effects of sulforaphane on gastric carcinoma cells
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Sulforaphane (SFN), a natural compound derived from cruciferous vegetables, has been proved to possess potent anti-cancer activity. SMYD3 is a histone methyltransferase which is closely related to the proliferation and migration of cancer cells. This study showed that SFN could dose-dependently induce cell cycle arrest, stimulate apoptosis, and inhibit proliferation and migration of gastric carcinoma cells. Accompanied with these anti-cancer effects, SMYD3 and its downstream genes, myosin regulatory light chain 9, and cysteine-rich angiogenic inducer 61, was downregulated by SFN. Furthermore, overexpression of SMYD3 via transfection could abolish the effects of SFN, suggesting that SMYD3 might be an important mediator of SFN. To the best of our knowledge, this is the first report describing the role of SMYD3 in the anti-cancer of SFN. These findings might throw light on the development of novel anti-cancer drugs and functional food using SFN-rich cruciferous vegetables.
KeywordsSulforaphane SET and MYND domain containing 3 Cell cycle Apoptosis Migration
This work was supported by grants from the National Natural Science Foundation of China (Nos. 31470816; 31300642), the College Students’ Innovation and Entrepreneurship Training Program of Tianjin (No. 201510057057) and the Young Teachers’ Innovation Fund of Tianjin University of Science and Technology (No. 2016LG06).
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
- 1.Bayat Mokhtari R, Baluch N, Homayouni TS, Morgatskaya Z, Kumar S, Kazemi P, Yeger H. The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review. J Cell Commun Signal. Epub ahead of print (2017).Google Scholar
- 6.Xu C, Shen G, Yuan X, Kim JH, Gopalkrishnan A, Keum YS, Nair S, Kong AN. ERK and JNK signaling pathways are involved in the regulation of activator protein 1 and cell death elicited by three isothiocyanates in human prostate cancer PC-3 cells. Carcinogenesis. 27: 437-445 (2006).CrossRefPubMedGoogle Scholar
- 12.Liu Y, Luo X, Deng J, Pan Y, Zhang L, Liang H. SMYD3 overexpression was a risk factor in the biological behavior and prognosis of gastric carcinoma. Tumour Biol. (2014).Google Scholar
- 27.Komatsu S, Ichikawa D, Hirajima S, Nagata H, Nishimura Y, Kawaguchi T, Miyamae M, Okajima W, Ohashi T, Konishi H, Shiozaki A, Fujiwara H, Okamoto K, Tsuda H, Imoto I, Inazawa J, Otsuji E. Overexpression of SMYD2 contributes to malignant outcome in gastric cancer. Br J Cancer. 112: 357-364 (2015).CrossRefPubMedGoogle Scholar
- 29.Zeng B, Li Z, Chen R, Guo N, Zhou J, Zhou Q, Lin Q, Cheng D, Liao Q, Zheng L, Gong Y. Epigenetic regulation of miR-124 by hepatitis C virus core protein promotes migration and invasion of intrahepatic cholangiocarcinoma cells by targeting SMYD3. FEBS Lett. 586: 3271-8 (2012).CrossRefPubMedGoogle Scholar
- 32.Zhang C, Luo X, Liu L, Guo S, Zhao W, Mu A, Liu Z, Wang N, Zhou H, Zhang T. Myocardin-related transcription factor A is up-regulated by 17beta-estradiol and promotes migration of MCF-7 breast cancer cells via transactivation of MYL9 and CYR61. Acta Biochim Biophys Sin (Shanghai). 45: 921-7 (2013).CrossRefPubMedGoogle Scholar
- 36.Huang YQ, Han ZD, Liang YX, Lin ZY, Ling XH, Fu X, Cai C, Bi XC, Dai QS, Chen JH, He HC, Chen YR, Jiang FN, Zhong WD. Decreased expression of myosin light chain MYL9 in stroma predicts malignant progression and poor biochemical recurrence-free survival in prostate cancer. Med Oncol. 31: 820 (2014).CrossRefPubMedGoogle Scholar