Molecular characterization of antitumor effects of the rhizome extract from Curcuma zedoaria on human esophageal carcinoma cells.
Curcuma zedoaria has been used as a traditional agent against malignant diseases. To elucidate detailed mechanisms producing such an activity, characterization and determination of molecular mechanisms of its antitumor effects was conducted. Inhibiting activities against cell proliferation, invasion and colony formation, and expression levels of corresponding molecules were investigated using human esophageal cancer TE-8 cells treated with the rhizome extract from C. zedoaria. Antitumor effect of the extract administered orally was also examined in tumor-bearing mice. The extract possessed strong anti-proliferation and invasion activities against TE-8 cells. Further, upregulated PTEN and downregulated phosphorylated Akt, mTOR and STAT3 expressions in the cells were induced shortly after treatment with the extract, followed by attenuation of FGFR1 and MMP-2, activation of caspase-9, caspase-3 and PARP, and suppression of Bcl-2 expressions, which led the cells to apoptotic cell death. Furthermore, tumor formation in mice was significantly suppressed through the oral administration of the extract. Taken together, these results suggest that the C. zedoaria extract could be a promising agent against esophageal cancer.
Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan.
Yuni Elsa
YE
Hadisaputri
Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan.
Tatsuya
T
Miyazaki
Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan.
Shigemasa
S
Suzuki
Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan.
Norio
N
Kubo
Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Bandung, Indonesia.
Ade
A
Zuhrotun
Department of Molecular and Cellular Pharmacology, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan.
Takehiko
T
Yokobori
Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Bandung, Indonesia.
Rizky
R
Abdulah
Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan.
Shin
S
Yazawa
Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan.
Hiroyuki
H
Kuwano
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D030024:Curcuma; D004938:Esophageal Neoplasms / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010936:Plant Extracts / Q000494:pharmacology*; D027343:Rhizome; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts