[Antitumor effect and mechanism of shikonin derivative SYUNZ-7].
OBJECTIVE
Natural shikonin compounds and their derivatives have cytotoxicity and antitumor effects. This study was to explore in vitro and in vivo antitumor effects of SYUNZ-7 [2 or 3, 11-bis(phenylsulfanyl)-6-isohexenylnaphthazarin] and the mechanisms.


METHODS
In vitro antiproliferation effects of SYUNZ-7 on human lung adenocarcinoma cell line GLC-82, human nasopharyngeal cancer cell line CNE2, human oral cavity cancer cell line KB, human gastric cancer cell line MGC-803 and human hepatocellular cancer cell line HepG2 were tested by MTT assay. In vivo antitumor effect of SYUNZ-7 was tested using ascitic cancer EAC xenograft in mice and CNE2 xenograft in nude mice models. Cell apoptosis and cell cycle distribution were assessed by flow cytometry. The in vivo effect of SYUNZ-7 on angiogenesis was detected by immunohistochemistry.


RESULTS
The 50% inhibitory concentrations (IC(50)) of SYUNZ-7 to GLC-82, CNE2, KB, MGC-803, and HepG2 cells were (2.18+/-0.04) microg/ml, (4.17+/-0.09) microg/ml, (5.41+/-0.10) microg/ml, (6.41+/-0.14) microg/ml, and (9.99+/-0.21) microg/ml, respectively. Under the treatment of 1, 2, 4, and 8 mg/kg of SYUNZ-7, the inhibitory rates of EAC xenografts in mice were (40.5+/-0.14)%, (50.9+/-2.3)%, (61.7+/-1.8)%, and (65.6+/-7.4)%, respectively (P<0.01). Under the treatment of 1, 2, and 4 mg/kg of SYUNZ-7, the inhibitory rates of CNE2 xenografts in nude mice were 24.7%, 38.3%, and 41.2%, respectively (P<0.05). SYUNZ-7 induced apoptosis of CNE2 cells in time- and concentration-dependent manners, and blocked the transition of CNE2 cells from S to G(2)/M phase. SYUNZ-7 also inhibited the angiogenesis of CNE2 xenografts in nude mice in a concentration-dependent manner.


CONCLUSIONS
SYUNZ-7 has strong in vivo and in vitro antitumor effects which are related to inducing cell apoptosis, blocking cell cycle, and inhibiting angiogenesis of tumor.
Huang
He
H
State Key Laboratory of Oncology in Southern China, Guangzhou, Guangdong 510060, P. R. China.
Xie
Bing-Fen
BF
Zhu
Xiao-Feng
XF
Feng
Gong-Kan
GK
Zhou
Jun-Min
JM
Wang
Yi
Y
Wu
Hai-Qiang
HQ
Huang
Zhi-Shu
ZS
Gu
Lian-Quan
LQ
Liu
Zong-Chao
ZC
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009303:Nasopharyngeal Neoplasms / Q000098:blood supply / Q000473:pathology*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*
D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; C522372:SYUNZ-7; C016101:shikonin