Growth inhibition and induction of apoptosis in human oral squamous cell carcinoma Tca-8113 cell lines by Shikonin was partly through the inactivation of NF-kappaB pathway.
Shikonin, a naphthoquinone pigment isolated from the Chinese herbal therapeutic, Zicao, has been shown to exhibit antioxidant and anticancer effects. In this study, its ability to induce apoptosis in cultured Tca-8113 oral cancer cells was studied. Treatment of the Tca-8113 cells with a variety of concentrations of Shikonin (10-40 microm) resulted in dose- and time-dependent sequences of events marked by apoptosis, as shown by the loss of cell viability, chromatin condensation, internucleosomal DNA fragmentation and sub-G1 phase accumulation. Furthermore, apoptosis in the Tca-8113 cells was accompanied by the activation of protease caspase-8, -9, -3 and low expression of Bcl-2 protein. Interestingly, inactivation of the NF-kappaB pathway was found in shikonin-induced apoptosis in Tca-8113 cells. These results raise the possibility that the anti-tumor effects of Shikonin in Tca-8113 cells are at least partly through the inactivation of the NF-kappaB pathway and subsequent activation of protease caspase family. Pharmacological inhibition of the NF-kappaB activity by Shikonin might be a powerful treatment option for OSCC in which activation of NF-kappaB plays a critical role in tumor growth and progression.
Min
Ruan
R
Department of Oral and Maxillofacial Surgery, Affiliated No. 9 People's Hospital, College of Medicine, Shanghai Jiao Tong University, Shanghai 200011, PRC.
Tong
Ji
J
Wenjun
Yang
Y
Wenhu
Duan
D
Xiaojian
Zhou
Z
Jiacai
He
H
Jian
Zhou
Z
Wantao
Chen
C
Chenping
Zhang
Z
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000032:analysis; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; C016101:shikonin; D004247:DNA; D020169:Caspases