Musk ketone induces apoptosis of gastric cancer cells via downregulation of sorbin and SH3 domain containing 2

An,Juan; Wang,Haiyan; Ma,Xiaoming; Hu,Binwen; Yan,Yunfei; Yan,Yupeng; Su,Zhanhai

doi:10.3892/mmr.2021.12089

Musk ketone induces apoptosis of gastric cancer cells via downregulation of sorbin and SH3 domain containing 2

Authors:
- Juan An
- Haiyan Wang
- Xiaoming Ma
- Binwen Hu
- Yunfei Yan
- Yupeng Yan
- Zhanhai Su
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Affiliations: Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai 810016, P.R. China, Department of Gastrointestinal Tumor Surgery, The Affiliated Hospital of Qinghai University, Xining, Qinghai 810016, P.R. China
Published online on: April 13, 2021 https://doi.org/10.3892/mmr.2021.12089
Article Number: 450
Copyright: © An et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Musk ketone exerts antiproliferative effects on several types of cancer, such as lung and breast cancer. However, the effects and underlying mechanisms of action of musk ketone in gastric cancer (GC) are poorly understood. The present study aimed to investigate the effects of musk ketone in GC cells. The present study indicated that musk ketone exerted significant anticancer effects on GC cells. The IC₅₀ values of musk ketone were 4.2 and 10.06 µM in AGS and HGC‑27 cells, respectively. Low dosage of musk ketone significantly suppressed the proliferation and colony formation of AGS and HGC‑27 cells. Cell cycle arrest and apoptosis were induced by musk ketone. Furthermore, microarray data indicated that musk ketone treatment led to downregulation of various genes, including sorbin and SH3 domain containing 2 (SORBS2). Reverse transcription‑quantitative PCR and immunoblotting results indicated that musk ketone repressed mRNA and protein expression levels of SORBS2. It was also shown that knockdown of SORBS2 inhibited the proliferation and colony formation of HGC‑27 cells. The antiproliferative effects of musk ketone were decreased in HGC‑27 cells with SORBS2 silencing. In summary, the present study indicated that musk ketone suppressed the proliferation and growth of GC partly by downregulating SORBS2 expression.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2020. CA Cancer J Clin. 70:7–30. 2020. View Article : Google Scholar : PubMed/NCBI
2	Van Cutsem E, Sagaert X, Topal B, Haustermans K and Prenen H: Gastric cancer. Lancet. 388:2654–2664. 2016. View Article : Google Scholar : PubMed/NCBI
3	Sexton R, Al Hallak M, Diab M and Azmi A: Gastric cancer: A comprehensive review of current and future treatment strategies. Cancer Metastasis Rev. 39:1179–1203. 2020. View Article : Google Scholar : PubMed/NCBI
4	Schulz C, Schütte K, Mayerle J and Malfertheiner P: The role of the gastric bacterial microbiome in gastric cancer: Helicobacter pylori and beyond. Therap Adv Gastroenterol. 12:17562848198940622019. View Article : Google Scholar : PubMed/NCBI
5	Ajani JA, D'Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, Denlinger CS, Fanta P, Farjah F, Fuchs CS, et al: Gastric cancer, version 3.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 14:1286–1312. 2016. View Article : Google Scholar : PubMed/NCBI
6	Liu T, Luo S, Libby P and Shi GP: Cathepsin L-selective inhibitors: A potentially promising treatment for COVID-19 patients. Pharmacol Ther. 213:1075872020. View Article : Google Scholar : PubMed/NCBI
7	Li C, Huang J, Cheng YC and Zhang YW: Traditional Chinese medicine in depression treatment: From molecules to systems. Front Pharmacol. 11:5862020. View Article : Google Scholar : PubMed/NCBI
8	Yang J, Zhu X, Yuan P, Liu J, Wang B and Wang G: Efficacy of traditional Chinese medicine combined with chemotherapy in patients with non-small cell lung cancer (NSCLC): A meta-analysis of randomized clinical trials. Support Care Cancer. 28:3571–3579. 2020. View Article : Google Scholar : PubMed/NCBI
9	Wang Y and Ha CY: Research progress on musk and artificial propagation technique of forest musk deer. Zhongguo Zhong Yao Za Zhi. 43:3806–3810. 2018.(In Chinese). PubMed/NCBI
10	Zhou Z, Dun L, Wei B, Gan Y, Liao Z, Lin X, Lu J, Liu G, Xu H, Lu C and An H: Musk ketone induces neural stem cell proliferation and differentiation in cerebral ischemia via activation of the PI3K/Akt signaling pathway. Neuroscience. 435:1–9. 2020. View Article : Google Scholar : PubMed/NCBI
11	Xu L and Cao Y: Native musk and synthetic musk ketone strongly induced the growth repression and the apoptosis of cancer cells. BMC Complement Altern Med. 16:5112016. View Article : Google Scholar : PubMed/NCBI
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
13	Yu G, Wang LG, Han Y and He QY: clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS. 16:284–287. 2012. View Article : Google Scholar : PubMed/NCBI
14	Liu Y, Gao M, An J, Wang X, Jia Y, Xu J, Zhu J, Cui J, Li W, Xing R, et al: Dysregulation of MiR-30a-3p/gastrin enhances tumor growth and invasion through STAT3/MMP11 pathway in gastric cancer. Onco Targets Ther. 13:8475–8493. 2020. View Article : Google Scholar : PubMed/NCBI
15	Yang L, Li J, Hu Z, Fan X, Cai T, Zhou H and Pan H: A systematic review of the mechanisms underlying treatment of gastric precancerous lesions by traditional Chinese medicine. Evid Based Complement Alternat Med. 2020:91547382020.PubMed/NCBI
16	Wu F, Liu W, Feng H, Long L, Hou L and Hou C: Application of traditional chinese medicines in postoperative abdominal adhesion. Evid Based Complement Alternat Med. 2020:80734672020. View Article : Google Scholar : PubMed/NCBI
17	Tu Y: The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat Med. 17:1217–1220. 2011. View Article : Google Scholar : PubMed/NCBI
18	Wang J, Xu C, Wong YK, Liao FL, Jiang T and Tu Y: Malaria eradication. Lancet. 395:e692020. View Article : Google Scholar : PubMed/NCBI
19	Tu T: Artemisinin-A gift from traditional Chinese medicine to the world (nobel lecture). Angew Chem Int Ed Engl. 55:10210–10226. 2016. View Article : Google Scholar : PubMed/NCBI
20	Zheng GQ, Kenney PM and Lam LK: Isolation and biological evaluation of potential cancer chemopreventive agents from ambrette musk residue. J Pharm Sci. 81:950–953. 1992. View Article : Google Scholar : PubMed/NCBI
21	Api AM, Pfitzer EA and San RH: An evaluation of genotoxicity tests with Musk ketone. Food Chem Toxicol. 34:633–638. 1996. View Article : Google Scholar : PubMed/NCBI
22	Sanger JM, Wang J, Gleason LM, Chowrashi P, Dube DK, Mittal B, Zhukareva V and Sanger JW: Arg/Abl-binding protein, a Z-body and Z-band protein, binds sarcomeric, costameric, and signaling molecules. Cytoskeleton (Hoboken). 67:808–823. 2010. View Article : Google Scholar : PubMed/NCBI
23	Kioka N, Ueda K and Amachi T: Vinexin, CAP/ponsin, ArgBP2: A novel adaptor protein family regulating cytoskeletal organization and signal transduction. Cell Struct Funct. 27:1–7. 2002. View Article : Google Scholar : PubMed/NCBI
24	Han L, Huang C and Zhang S: The RNA-binding protein SORBS2 suppresses hepatocellular carcinoma tumourigenesis and metastasis by stabilizing RORA mRNA. Liver Int. 39:2190–2203. 2019. View Article : Google Scholar : PubMed/NCBI
25	Yan B, Peng Z and Xing C: SORBS2, mediated by MEF2D, suppresses the metastasis of human hepatocellular carcinoma by inhibitiing the c-Abl-ERK signaling pathway. Am J Cancer Res. 9:2706–2718. 2019.PubMed/NCBI
26	Zhao L, Wang W, Huang S, Yang Z, Xu L, Yang Q, Zhou X, Wang J, Shen Q, Wang C, et al: The RNA binding protein SORBS2 suppresses metastatic colonization of ovarian cancer by stabilizing tumor-suppressive immunomodulatory transcripts. Genome Biol. 19:352018. View Article : Google Scholar : PubMed/NCBI
27	Jie R, Zhu P, Zhong J, Zhang Y and Wu H: LncRNA KCNQ1OT1 affects cell proliferation, apoptosis and fibrosis through regulating miR-18b-5p/SORBS2 axis and NF-ĸB pathway in diabetic nephropathy. Diabetol Metab Syndr. 12:772020. View Article : Google Scholar : PubMed/NCBI
28	Tong Y, Li Y, Gu H, Wang C, Liu F, Shao Y and Li F: HSF1, in association with MORC2, downregulates ArgBP2 via the PRC2 family in gastric cancer cells. Biochim Biophys Acta Mol Basis Dis. 1864:1104–1114. 2018. View Article : Google Scholar : PubMed/NCBI