Novel ent-Kaurane Diterpenoid from Rubus corchorifolius L. f. Inhibits Human Colon Cancer Cell Growth via Inducing Cell Cycle Arrest and Apoptosis.
The tender leaves of Rubus corchorifolius L. f. have been consumed as tea for drinking in China since ancient times. In this study, a novel ent-kaurane diterpenoid was isolated and identified from R. corchorifolius L. f. leaves as ent-kaur-2-one-16β,17-dihydroxy-acetone-ketal (DEK). DEK suppressed the growth of HCT116 human colon cancer cells with an IC50value of 40 ± 0.21 μM, while it did not cause significant growth inhibition on CCD-18Co human colonic myofibroblasts at up to100 μM. Moreover, DEK induced extensive apoptosis and S phase cell cycle arrest in the colon cancer cells. Accordingly, DEK caused profound effects on multiple signaling proteins associated with cell proliferation, cell death, and inflammation. DEK significantly upregulated the expression levels of pro-apoptotic proteins such as cleaved caspase-3, cleaved caspase-9, cleaved PARP, p53, Bax, and tumor suppressor p21Cip1/Waf1, downregulated the levels of cell cycle regulating proteins such as cyclinD1, CDK2, and CDK4 and carcinogenic proteins such as EGFR and COX-2, and suppressed the activation of Akt. Overall, our results provide a basis for using DEK as a potential chemopreventive agent against colon carcinogenesis.
College of Food Science, South China Agricultural University , Guangzhou 510642, People's Republic of China.|Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.|College of Public Health, Guangzhou Medical University , Guangzhou 511436, People's Republic of China.
Xuexiang
X
Chen
Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
Xian
X
Wu
Pharmacy College, Hunan University of Traditional Chinese Medicine , Changsha 410007, People's Republic of China.
Wen
W
Ouyang
Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
Min
M
Gu
Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
Zili
Z
Gao
Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
Mingyue
M
Song
College of Food Science, South China Agricultural University , Guangzhou 510642, People's Republic of China.|Guangdong Province Engineering Research Center for Bioactive Natural Products , Guangzhou 510642, People's Republic of China.
Yunjiao
Y
Chen
College of Food Science, South China Agricultural University , Guangzhou 510642, People's Republic of China.|Guangdong Province Engineering Research Center for Bioactive Natural Products , Guangzhou 510642, People's Republic of China.
Yanyin
Y
Lin
College of Food Science, South China Agricultural University , Guangzhou 510642, People's Republic of China.|Guangdong Province Engineering Research Center for Bioactive Natural Products , Guangzhou 510642, People's Republic of China.
Yong
Y
Cao
Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
Hang
http://orcid.org/0000-0001-6194-2796
H
Xiao
D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003106:Colon / Q000166:cytology* / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D065856:Rubus / Q000737:chemistry*
D045786:Diterpenes, Kaurane; D010936:Plant Extracts
Rubus corchorifolius L.f.; apoptosis; cell cycle; colon cancer; ent-kaur-2-one-16β,17-dihydroxy-acetone-ketal