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A novel curcumin derivative CL-6 exerts antitumor effect in human gastric cancer cells by inducing apoptosis through Hippo-YAP signaling pathway.
Onco Targets Ther 2019; 12:2259-2269OT

Abstract

Purpose

Gastric carcinoma is the second most frequently diagnosed cancer and leading cause of cancer death in China. As a new generation of cancer therapeutic drug, CL-6, a curcumin derivative, shows better bioavailability than curcumin, which has shown anticancer effects in gastric cancer (GC). However, whether CL-6 shows similar activities in GC has not been examined.

Materials and methods

Cell proliferation assay, colony-forming assay, flow cytometric analysis, wound healing assay, and Transwell invasion assay were performed to examine the effects of CL-6 on proliferation, apoptosis, migration, and invasion on human AGS and MGC-803 cell lines. Western blot was used to evaluate protein levels of Bax, Bcl-2, YAP, p-YAP, and Lats, and gene expression was measured by real-time quantitative PCR (RT-qPCR).

Results

CL-6 dose dependently reduced proliferation, increased apoptosis, and inhibited the migration and invasion abilities of AGS and MGC-803 cells. CL-6 also increased levels of pro-apoptotic protein Bax, decreased levels of antiapoptotic protein Bcl-2, and increased the Bax/Bcl-2 ratio. CL-6 treatment also inhibited YAP and YAP protein and mRNA expression, while it induced the expression of Lats and p-YAP (Ser127).

Conclusion

CL-6 induces apoptosis of GC cells by activating the Hippo-YAP signaling pathway. These results indicate the therapeutic potential of the novel curcumin derivative CL-6 in GC.

Authors+Show Affiliations

Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China, fame198288@126.com; zzq652992@163.com. The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China.Department of Breast Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China.Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China, fame198288@126.com; zzq652992@163.com. The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China.Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China, fame198288@126.com; zzq652992@163.com. The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China.Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China, fame198288@126.com; zzq652992@163.com. The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China.School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, People's Republic of China.Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China, fame198288@126.com; zzq652992@163.com. The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China.Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China, fame198288@126.com; zzq652992@163.com. The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China.Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China, fame198288@126.com; zzq652992@163.com. The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China.Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China, fame198288@126.com; zzq652992@163.com.Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, People's Republic of China, fame198288@126.com; zzq652992@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30988630

Citation

Ye, Chenmin, et al. "A Novel Curcumin Derivative CL-6 Exerts Antitumor Effect in Human Gastric Cancer Cells By Inducing Apoptosis Through Hippo-YAP Signaling Pathway." OncoTargets and Therapy, vol. 12, 2019, pp. 2259-2269.
Ye C, Wang W, Xia G, et al. A novel curcumin derivative CL-6 exerts antitumor effect in human gastric cancer cells by inducing apoptosis through Hippo-YAP signaling pathway. Onco Targets Ther. 2019;12:2259-2269.
Ye, C., Wang, W., Xia, G., Yu, C., Yi, Y., Hua, C., ... Zheng, Z. (2019). A novel curcumin derivative CL-6 exerts antitumor effect in human gastric cancer cells by inducing apoptosis through Hippo-YAP signaling pathway. OncoTargets and Therapy, 12, pp. 2259-2269. doi:10.2147/OTT.S196914.
Ye C, et al. A Novel Curcumin Derivative CL-6 Exerts Antitumor Effect in Human Gastric Cancer Cells By Inducing Apoptosis Through Hippo-YAP Signaling Pathway. Onco Targets Ther. 2019;12:2259-2269. PubMed PMID: 30988630.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel curcumin derivative CL-6 exerts antitumor effect in human gastric cancer cells by inducing apoptosis through Hippo-YAP signaling pathway. AU - Ye,Chenmin, AU - Wang,Wenqian, AU - Xia,Guojun, AU - Yu,Chengyang, AU - Yi,Yongdong, AU - Hua,Chunyan, AU - Tu,Fuyang, AU - Shen,Leibin, AU - Chen,Canjin, AU - Sun,Weijian, AU - Zheng,Zhiqiang, Y1 - 2019/03/27/ PY - 2019/4/17/entrez PY - 2019/4/17/pubmed PY - 2019/4/17/medline KW - Hippo–YAP pathway KW - YAP KW - apoptosis KW - gastric cancer KW - migration SP - 2259 EP - 2269 JF - OncoTargets and therapy JO - Onco Targets Ther VL - 12 N2 - Purpose: Gastric carcinoma is the second most frequently diagnosed cancer and leading cause of cancer death in China. As a new generation of cancer therapeutic drug, CL-6, a curcumin derivative, shows better bioavailability than curcumin, which has shown anticancer effects in gastric cancer (GC). However, whether CL-6 shows similar activities in GC has not been examined. Materials and methods: Cell proliferation assay, colony-forming assay, flow cytometric analysis, wound healing assay, and Transwell invasion assay were performed to examine the effects of CL-6 on proliferation, apoptosis, migration, and invasion on human AGS and MGC-803 cell lines. Western blot was used to evaluate protein levels of Bax, Bcl-2, YAP, p-YAP, and Lats, and gene expression was measured by real-time quantitative PCR (RT-qPCR). Results: CL-6 dose dependently reduced proliferation, increased apoptosis, and inhibited the migration and invasion abilities of AGS and MGC-803 cells. CL-6 also increased levels of pro-apoptotic protein Bax, decreased levels of antiapoptotic protein Bcl-2, and increased the Bax/Bcl-2 ratio. CL-6 treatment also inhibited YAP and YAP protein and mRNA expression, while it induced the expression of Lats and p-YAP (Ser127). Conclusion: CL-6 induces apoptosis of GC cells by activating the Hippo-YAP signaling pathway. These results indicate the therapeutic potential of the novel curcumin derivative CL-6 in GC. SN - 1178-6930 UR - https://www.unboundmedicine.com/medline/citation/30988630/A_novel_curcumin_derivative_CL_6_exerts_antitumor_effect_in_human_gastric_cancer_cells_by_inducing_apoptosis_through_Hippo_YAP_signaling_pathway_ L2 - https://dx.doi.org/10.2147/OTT.S196914 DB - PRIME DP - Unbound Medicine ER -