β,β-Dimethylacrylshikonin exerts antitumor activity via Notch-1 signaling pathway in vitro and in vivo.
β,β-Dimethylacrylshikonin (DA) is a major component of Radix Lithospermum erythrorhizon and has various biological activities. We have investigated the inhibitory effect of DA on the growth of hepatocellular carcinoma in vitro and in vivo. Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis. Hence, perturbed Notch signaling may contribute to tumorigenesis. In the present study, we evaluated whether DA could be an effective inhibitor on cell growth in human gastric cancer cell line, and also the molecular mechanisms. Using multiple cellular and molecular approaches such as MTT assay, colony formation assay, DAPI staining, flow cytometry, real-time PCR and Western blot analysis, we found that DA inhibited cell growth in a dose- and time-dependent manner. Biochemical analysis revealed the involvement of cell cycle regulated proteins in DA-mediated of G₀-G₁ arrest of SGC-7901 cells. Furthermore, DA treatment led to reduced Notch-1 activation, expression of Jagged-1 and its downstream target Hes-1 in vitro and in vivo. Our data demonstrated that DA is a potent inhibitor of progression of gastric cancer cells, which could be due to attenuation of Notch-1. We also suggest that DA could be further developed as a potential therapeutic agent for the treatment of gastric cancer.
Department of Pharmacology, Preclinical and Forensic Medical College, Sichuan University, Chengdu 610041, China.
Shao
S
Zhen-Jun
Zhang
Z
Yuan-Yuan
Fan
F
Ying-Ying
Jin
J
Shao-Ju
Yan
Y
Jiao
Zheng
Z
Xiao-Wei
Chen
C
Jian
Xiong
X
Yao
Zhou
Z
Li-Ming
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy*; D014183:Transplantation, Heterologous
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D009285:Naphthoquinones; D051881:Receptor, Notch1; C032573:beta, beta-dimethylacrylshikonin