title: Baicalein inhibits agonist- and tumor cell-induced platelet aggregation while suppressing pulmonary tumor metastasis via cAMP-mediated VASP phosphorylation along with impaired MAPKs and PI3K-Akt activation.
abstract: Recently, the importance of platelet activation in cancer metastasis has become generally accepted. As a result, the development of new platelet inhibitors with minimal adverse effects is now a promising area of targeted cancer therapy. Baicalein is a functional ingredient derived from the root of Scutellaria baicalensis Georgi, a plant used intraditional medicine. The pharmacological effects of this compound including anti-oxidative and anti-inflammatory activities have already been demonstrated. However, its effects on platelet activation are unknown. We therefore investigated the effects of baicalein on ligand-induced platelet aggregation and pulmonary cancer metastasis. In the present study, baicalein inhibited agonist-induced platelet aggregation, granule secretion markers (P-selectin expression and ATP release), [Ca(2+)]i mobilization, and integrin αIIbβ3 expression. Additionally, baicalein attenuated ERK2, p38, and Akt activation, and enhanced VASP phosphorylation. Indeed, baicalein was shown to directly inhibit PI3K kinase activity. Moreover, baicalein attenuated the platelet aggregation induced by C6 rat glioma tumor cells in vitro and suppressed CT26 colon cancer metastasis in mice. These features indicate that baicalein is a potential therapeutic drug for the prevention of cancer metastasis.
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
authors.forename: Sung Dae
authors.initials: SD
authors.lastname: Kim
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
authors.forename: Young Ji
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
authors.forename: Ji Sue
authors.initials: JS
authors.lastname: Baik
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
authors.forename: Joeng Yoon
authors.initials: JY
authors.lastname: Han
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
authors.forename: Chang Geun
authors.initials: CG
authors.lastname: Lee
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
authors.forename: Kyu
authors.initials: K
authors.lastname: Heo
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
authors.forename: You Soo
authors.initials: YS
authors.lastname: Park
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
authors.forename: Joong Sun
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Laboratory of Veterinary Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Hyun Dong
authors.initials: HD
authors.lastname: Ji
authors.affiliation: Cardiovascular Product Evaluation Center, College of Medicine, Yonsei University, Seoul 120-752, Republic of Korea.
authors.forename: Se Il
authors.initials: SI
authors.lastname: Park
authors.affiliation: Laboratory of Veterinary Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: rheemh@knu.ac.kr.
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea; Department of Radiation Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea; Department of Radiaton Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea. Electronic address: kmyang@dirams.re.kr.
authors.forename: Kwangmo
authors.initials: K
authors.lastname: Yang
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044950:Flavanones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D023041:Xenograft Model Antitumor Assays; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D000242:Cyclic AMP; D004791:Enzyme Inhibitors; D044950:Flavanones; D008840:Microfilament Proteins; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt; D000098662:Vasodilator-Stimulated Phosphoprotein; C006680:baicalein
keywords: Baicalein; Metastasis; PI-3K; Platelets; TCIPA