PMID- 38236367 OWN - NLM STAT- MEDLINE DCOM- 20240119 LR - 20240202 IS - 1573-4978 (Electronic) IS - 0301-4851 (Linking) VI - 51 IP - 1 DP - 2024 Jan 18 TI - In vitro and in vivo anti-tumor effect of Trichobakin fused with urokinase-type plasminogen activator ATF-TBK. PG - 130 LID - 10.1007/s11033-023-09036-6 [doi] AB - BACKGROUND: Trichobakin (TBK), a member of type I ribosome-inactivating proteins (RIPs), was first successfully cloned from Trichosanthes sp Bac Kan 8-98 in Vietnam. Previous study has shown that TBK acts as a potential protein synthesis inhibitor; however, the inhibition efficiency and specificity of TBK on cancer cells remain to be fully elucidated. METHODS AND RESULTS: In this work, we employed TBK and TBK conjugated with a part of the amino-terminal fragment (ATF) of the urokinase-type plasminogen activator (uPA), which contains the Omega-loop that primarily interacts with urokinase-type plasminogen activator receptor, and can be a powerful carrier in the drug delivery to cancer cells. Four different human tumor cell lines and BALB/c mice bearing Lewis lung carcinoma cells (LLC) were used to evaluate the role of TBK and ATF-TBK in the inhibition of tumor growth. Here we showed that the obtained ligand fused RIP (ATF-TBK) reduced the growth of four human cancer cell lines in vitro in the uPA receptor level-dependent manner, including the breast adenocarcinoma MDA-MB 231 cells and MCF7 cells, the prostate carcinoma LNCaP cells and the hepatocellular carcinoma HepG2 cells. Furthermore, the conjugate showed anti-tumor activity and prolonged the survival time of tumor-bearing mice. The ATF-TBK also did not cause the death of mice with doses up to 48 mg/kg, and they were not significantly distinct on parameters of hematology and serum biochemistry between the control and experiment groups. CONCLUSIONS: In conclusion, ATF-TBK reduced the growth of four different human tumor cell lines and inhibited lung tumor growth in a mouse model with little side effects. Hence, the ATF-TBK may be a target to consider as an anti-cancer agent for clinical trials. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Pham, Dan Duc AU - Pham DD AD - Institute of Biotechnology (IBT), Vietnam Academy of Science and Technology (VAST), 18, Hoang Quoc Viet Road, Cau Giay, Hanoi, Vietnam. FAU - Pham, Thi Hue AU - Pham TH AD - Institute of Biotechnology (IBT), Vietnam Academy of Science and Technology (VAST), 18, Hoang Quoc Viet Road, Cau Giay, Hanoi, Vietnam. FAU - Bui, Thi Huyen AU - Bui TH AD - Institute of Biotechnology (IBT), Vietnam Academy of Science and Technology (VAST), 18, Hoang Quoc Viet Road, Cau Giay, Hanoi, Vietnam. FAU - Britikova, Elena V AU - Britikova EV AD - Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 220141, Minsk, Belarus. FAU - Britikov, Vladimir V AU - Britikov VV AD - Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 220141, Minsk, Belarus. FAU - Bocharov, Eduard V AU - Bocharov EV AD - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia, 117997. FAU - Usanov, Sergey A AU - Usanov SA AD - Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 220141, Minsk, Belarus. FAU - Phan, Van Chi AU - Phan VC AD - Institute of Biotechnology (IBT), Vietnam Academy of Science and Technology (VAST), 18, Hoang Quoc Viet Road, Cau Giay, Hanoi, Vietnam. FAU - Le, Thi Bich Thao AU - Le TBT AD - Institute of Biotechnology (IBT), Vietnam Academy of Science and Technology (VAST), 18, Hoang Quoc Viet Road, Cau Giay, Hanoi, Vietnam. lethao@ibt.ac.vn. AD - Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam. lethao@ibt.ac.vn. LA - eng GR - QTRU05.01/21-23/The Vietnam Academy of Science and Technology/ GR - VINIF.2023.STS.28/The Postdoctoral Scholarship Programme of Vingroup Innovation Foundation (VINIF)/ GR - capital HA, Cyrillic20capital IE, Cyrilliccapital A, Cyrillic-027/BRFBR/ GR - 20-54-81015/RFBR/ PT - Journal Article DEP - 20240118 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) SB - IM MH - Humans MH - Male MH - Animals MH - Mice MH - Urokinase-Type Plasminogen Activator MH - Drug Delivery Systems MH - *Prostatic Neoplasms MH - *Lung Neoplasms MH - Cell Line, Tumor OTO - NOTNLM OT - ATF-TBK OT - Cytotoxic activity OT - Ribosome inactivating protein (RIP) OT - Trichobakin (TBK) OT - Urokinase plasminogen activator (uPA) EDAT- 2024/01/18 12:42 MHDA- 2024/01/19 06:42 CRDT- 2024/01/18 11:19 PHST- 2023/08/22 00:00 [received] PHST- 2023/11/28 00:00 [accepted] PHST- 2024/01/19 06:42 [medline] PHST- 2024/01/18 12:42 [pubmed] PHST- 2024/01/18 11:19 [entrez] AID - 10.1007/s11033-023-09036-6 [pii] AID - 10.1007/s11033-023-09036-6 [doi] PST - epublish SO - Mol Biol Rep. 2024 Jan 18;51(1):130. doi: 10.1007/s11033-023-09036-6.