N-(3-hydroxymethyl-β-carboline-1-yl-ethyl- 2-yl)-l-Phe: development toward a nanoscaled antitumor drug capable of treating complicated thrombosis and inflammation.
It is well documented that the surfaces of cancer cells, activated platelets and inflammatory cells are rich in P-selectin.N-(3-hydroxymethyl-β-carboline-1-yl-ethyl-2-yl)-l-Phe (HMCEF) is a P-selectin inhibitor capable of simultaneously inhibiting thrombosis and inflammation. Based on the knowledge that P-selectin is a common target for antithrombotic, anti-inflammatory and antitumor drugs, the aim of this study article was to estimate the possibility of HMCEF as a nanoscaled antitumor drug. Images of transmission electron micro scopy, scanning electron microscopy and atomic force microscopy proved that HMCEF forms nanoparticles with a diameter of <120 nm that promote delivery in blood circulation. In vitro HMCEF intercalates into calf thymus DNA, cuts off DNA pBR22 and inhibits the proliferation of cancer cells. In vivo HMCEF dose dependently (0.2, 2 and 200 nmol/kg per day) slows tumor growth in treated S180 mice, and has a minimal effective dose of 2 nmol/kg per day. At 200 nmol/kg per day, HMCEF does not affect the liver and the kidney of the treated S180 mice, and at 20,000 nmol/kg HMCEF does not affect the liver and the kidney of the treated healthy ICR mice. HMCEF is a promising antitumor drug, which is characterized by its high safety and efficacy in the prevention of the complications of thrombosis and inflammation in patients.
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs; Engineering Research Center of Endogenous Prophylactic, Ministry of Education of China; Beijing Laboratory of Biomedical Materials; College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
Jianhui
J
Wu
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs; Engineering Research Center of Endogenous Prophylactic, Ministry of Education of China; Beijing Laboratory of Biomedical Materials; College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
Ming
M
Zhao
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs; Engineering Research Center of Endogenous Prophylactic, Ministry of Education of China; Beijing Laboratory of Biomedical Materials; College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
Yuji
Y
Wang
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs; Engineering Research Center of Endogenous Prophylactic, Ministry of Education of China; Beijing Laboratory of Biomedical Materials; College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
Yaonan
Y
Wang
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs; Engineering Research Center of Endogenous Prophylactic, Ministry of Education of China; Beijing Laboratory of Biomedical Materials; College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
Haimei
H
Zhu
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs; Engineering Research Center of Endogenous Prophylactic, Ministry of Education of China; Beijing Laboratory of Biomedical Materials; College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
Shurui
S
Zhao
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs; Engineering Research Center of Endogenous Prophylactic, Ministry of Education of China; Beijing Laboratory of Biomedical Materials; College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
Lin
L
Gui
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs; Engineering Research Center of Endogenous Prophylactic, Ministry of Education of China; Beijing Laboratory of Biomedical Materials; College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
Xiaoyi
X
Zhang
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs; Engineering Research Center of Endogenous Prophylactic, Ministry of Education of China; Beijing Laboratory of Biomedical Materials; College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
Shiqi
S
Peng
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D053837:DNA Cleavage; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000150:complications / Q000188:drug therapy*
D000970:Antineoplastic Agents; D002243:Carbolines; C000618387:N-(3-hydroxymethyl-beta-carboline-1-yl-ethyl- 2-yl)-l-Phe; D010649:Phenylalanine; D004247:DNA; C427203:calf thymus DNA
P-selectin; anti-inflammation; antithrombosis; antitumor; nanomedicine