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Gossypetin Inhibits Solar-UV Induced Cutaneous Basal Cell Carcinoma Through Direct Inhibiting PBK/TOPK Protein Kinase.
Anticancer Agents Med Chem 2019; 19(8):1029-1036AA

Abstract

BACKGROUND

Skin photoaging, skin inflammation and skin cancer are related with excessive exposure to solar UV. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a member of the serine/threonine protein kinase, which regulates the signaling cascades of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal regulated kinase 1/2 (ERK1/2). PBK/TOPK plays a significant role in solar-UV-induced cutaneous basal cell carcinoma (BCC), and targeting PBK/TOPK can be supposed to treat and prevent cutaneous BCC.

METHODS

The pathological feature and the expression level of PBK/TOPK in cutaneous BCC tissues of human were studied in clinical samples. SUV-induced the phosphorylation of p38 MAPK and ERK1/2 were demonstrated ex vivo. Moreover, the interaction between Gossypetin and PBK/TOPK were detected by in vitro kinase assay and Microscale thermophoresis (MST) assay. Furthermore, the effect of Gossypetin to solar UV-induced the activity of PBK/TOPK were detected ex vivo and in vivo.

RESULTS

The clinical samples showed that the expression levels of PBK/TOPK, phosphor-p38 MAPK and phosphor- ERK1/2 were up-regulated in cutaneous BCC tissues of human. The expression of phosphor-p38 MAPK or phosphor-ERK1/2 increased in a dose and time dependent manner after solar UV treatment in HaCaT cells. MTT cytotoxicity assay results showed that Gossypetin has no effect on HaCaT cells. In vitro kinase assay and MST assay results showed that Gossypetin bound with PBK/TOPK and suppressed PBK/TOPK activity. Ex vivo results showed Gossypetin inhibited solar UV-induced phosphorylation of PBK/TOPK, p38 MAPK, ERK1/2 and H2AX by suppressing PBK/TOPK activity. In vivo test results indicated that Gossypetin suppressed solar UV-induced increase of PBK/TOPK, phosphor-p38 MAPK, phosphor-ERK1/2 and phosphor- H2AX in SKH-1 hairless mice.

CONCLUSION

Our data demonstrated that Gossypetin can alleviate solar-UV-induced cutaneous BCC by blocking PBK/TOPK, and Gossypetin could be a remarkable agent for treating solar-UV induced cutaneous basal cell carcinoma.

Authors+Show Affiliations

Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.Department of Biochemistry and Molecular Biology, Basic Medical Science of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30827262

Citation

Wang, Lijuan, et al. "Gossypetin Inhibits Solar-UV Induced Cutaneous Basal Cell Carcinoma Through Direct Inhibiting PBK/TOPK Protein Kinase." Anti-cancer Agents in Medicinal Chemistry, vol. 19, no. 8, 2019, pp. 1029-1036.
Wang L, Zhang Z, Ge R, et al. Gossypetin Inhibits Solar-UV Induced Cutaneous Basal Cell Carcinoma Through Direct Inhibiting PBK/TOPK Protein Kinase. Anticancer Agents Med Chem. 2019;19(8):1029-1036.
Wang, L., Zhang, Z., Ge, R., Zhang, J., Liu, W., Mou, K., ... Mu, X. (2019). Gossypetin Inhibits Solar-UV Induced Cutaneous Basal Cell Carcinoma Through Direct Inhibiting PBK/TOPK Protein Kinase. Anti-cancer Agents in Medicinal Chemistry, 19(8), pp. 1029-1036. doi:10.2174/1871520619666190301123131.
Wang L, et al. Gossypetin Inhibits Solar-UV Induced Cutaneous Basal Cell Carcinoma Through Direct Inhibiting PBK/TOPK Protein Kinase. Anticancer Agents Med Chem. 2019;19(8):1029-1036. PubMed PMID: 30827262.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gossypetin Inhibits Solar-UV Induced Cutaneous Basal Cell Carcinoma Through Direct Inhibiting PBK/TOPK Protein Kinase. AU - Wang,Lijuan, AU - Zhang,Zixi, AU - Ge,Rui, AU - Zhang,Jian, AU - Liu,Wenli, AU - Mou,Kuanhou, AU - Lv,Shemin, AU - Mu,Xin, PY - 2018/09/06/received PY - 2018/11/23/revised PY - 2019/02/04/accepted PY - 2019/3/5/pubmed PY - 2019/3/5/medline PY - 2019/3/5/entrez KW - Gossypetin KW - MAPK KW - PBK/TOPK KW - cutaneous basal cell carcinoma KW - microscale thermophoresis assay KW - solar-UV. SP - 1029 EP - 1036 JF - Anti-cancer agents in medicinal chemistry JO - Anticancer Agents Med Chem VL - 19 IS - 8 N2 - BACKGROUND: Skin photoaging, skin inflammation and skin cancer are related with excessive exposure to solar UV. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a member of the serine/threonine protein kinase, which regulates the signaling cascades of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal regulated kinase 1/2 (ERK1/2). PBK/TOPK plays a significant role in solar-UV-induced cutaneous basal cell carcinoma (BCC), and targeting PBK/TOPK can be supposed to treat and prevent cutaneous BCC. METHODS: The pathological feature and the expression level of PBK/TOPK in cutaneous BCC tissues of human were studied in clinical samples. SUV-induced the phosphorylation of p38 MAPK and ERK1/2 were demonstrated ex vivo. Moreover, the interaction between Gossypetin and PBK/TOPK were detected by in vitro kinase assay and Microscale thermophoresis (MST) assay. Furthermore, the effect of Gossypetin to solar UV-induced the activity of PBK/TOPK were detected ex vivo and in vivo. RESULTS: The clinical samples showed that the expression levels of PBK/TOPK, phosphor-p38 MAPK and phosphor- ERK1/2 were up-regulated in cutaneous BCC tissues of human. The expression of phosphor-p38 MAPK or phosphor-ERK1/2 increased in a dose and time dependent manner after solar UV treatment in HaCaT cells. MTT cytotoxicity assay results showed that Gossypetin has no effect on HaCaT cells. In vitro kinase assay and MST assay results showed that Gossypetin bound with PBK/TOPK and suppressed PBK/TOPK activity. Ex vivo results showed Gossypetin inhibited solar UV-induced phosphorylation of PBK/TOPK, p38 MAPK, ERK1/2 and H2AX by suppressing PBK/TOPK activity. In vivo test results indicated that Gossypetin suppressed solar UV-induced increase of PBK/TOPK, phosphor-p38 MAPK, phosphor-ERK1/2 and phosphor- H2AX in SKH-1 hairless mice. CONCLUSION: Our data demonstrated that Gossypetin can alleviate solar-UV-induced cutaneous BCC by blocking PBK/TOPK, and Gossypetin could be a remarkable agent for treating solar-UV induced cutaneous basal cell carcinoma. SN - 1875-5992 UR - https://www.unboundmedicine.com/medline/citation/30827262/Gossypetin_Inhibits_Solar_UV_Induced_Cutaneous_Basal_Cell_Carcinoma_Through_Direct_Inhibiting_PBK/TOPK_Protein_Kinase_ L2 - http://www.eurekaselect.com/170356/article DB - PRIME DP - Unbound Medicine ER -