Cytotoxic and Antitumor Effects of Curzerene from Curcuma longa.
Curzerene is a sesquiterpene and component used in oriental medicine. It was originally isolated from the traditional Chinese herbal medicineCurcumarhizomes. In this study, anticancer activity of curzerene was examined in bothin vitroandin vivomodels. The result of the MTT assay showed that curzerene exhibited antiproliferative effects in SPC-A1 human lung adenocarcinoma cells in a time-dependent and dose-dependent manner. The anticancer IC50s were 403.8, 154.8, and 47.0 µM for 24, 48, and 72 hours, respectively. The flow cytometry analysis indicated curzerene arrested the cells in the G2/M cell cycle and promoted or induced apoptosis of SPC-A1 cells. The percentage of cells arrested in the G2/M phase increased from 9.26 % in the control group cells to 17.57 % in the cells treated with the highest dose (100 µM) of curzerene. Western blot and RT-PCR analysis demonstrated that curzerene induced the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Tumor growth was significantly inhibited in SPC-A1 cell-bearing nude mice by using curzerene (135 mg/kg daily), meanwhile, curzerene did not significantly affect body mass and the organs of the mice, which may indicate that curzerene has limited toxicity and side effectsin vivo. In conclusion, curzerene could inhibit the proliferation of SPC-A1 human lung adenocarcinoma cells line in bothin vitroandin vivomodels. Focusing on its relationship with GSTA1, curzerene could induce the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Curzerene might be used as an anti-lung adenocarcinoma drug candidate compound for further development.
College of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
Youdi
Y
Wang
College of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
Jiahong
J
Li
Guangdong General Hospital, Guangzhou, China.
Jiquan
J
Guo
The Third Affiliated Hospital of Sun-Yat Shan University, Guangzhou, China.
Qiyou
Q
Wang
Guangdong General Hospital, Guangzhou, China.
Shuguang
S
Zhu
Novel Drug Screening Center, Department of Pharmacology, Guangdong Pharmaceutical University, Guangzhou, China.
Siyuan
S
Gao
College of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
Chen
C
Yang
College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Min
M
Wei
Novel Drug Screening Center, Department of Pharmacology, Guangdong Pharmaceutical University, Guangzhou, China.
Xuediao
X
Pan
Dshare Pharmaceutical Science & Technology Co., Ltd., Jiangsu, China.
Wei
W
Zhu
Guangdong Food and Drug Vocational College, Guangzhou, China.
Dongmei
D
Ding
The First Affiliated Hospital, Pharmaceutical University, Guangzhou, China.
Ruiping
R
Gao
The First Affiliated Hospital, Pharmaceutical University, Guangzhou, China.
Wei
W
Zhang
State Key laboratory of Oncology in Southern China, Sun-Yat Shan University Cancer Center, Guangzhou, China.
Junye
J
Wang
Novel Drug Screening Center, Department of Pharmacology, Guangdong Pharmaceutical University, Guangzhou, China.
Linquan
L
Zang
D000230:Adenocarcinoma / Q000188:drug therapy*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D030024:Curcuma / Q000737:chemistry*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010936:Plant Extracts / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D010936:Plant Extracts; D012717:Sesquiterpenes; C000609675:curzerene; C012596:turmeric extract; C484555:GSTA1 protein, human; D005982:Glutathione Transferase