Open AccessClove Extract Inhibits Tumor Growth and Promotes Cell Cycle Arrest and Apoptosis
Author(s) -
Haizhou Liu,
John C. Schmitz,
Jianteng Wei,
Shousong Cao,
Jan H. Beumer,
Sandra Strychor,
Linyou Cheng,
Ming Liu,
Cuicui Wang,
Ning Wu,
Xiangzhong Zhao,
Yuyan Zhang,
Joshua D. Liao,
Edward Chu,
Xiukun Lin
Publication year - 2014
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504014x13946388748910
Subject(s) - cell cycle , cell cycle checkpoint , apoptosis , biology , cell growth , in vivo , cell culture , western blot , pharmacology , cancer research , traditional medicine , medicine , biochemistry , genetics , microbiology and biotechnology , gene
Cloves ( Syzygium aromaticum ) have been used as a traditional Chinese medicinal herb for thousands of years. Cloves possess antiseptic, antibacterial, antifungal, and antiviral properties, but their potential anticancer activity remains unknown. In this study, we investigated the in vitro and in vivo antitumor effects and biological mechanisms of ethyl acetate extract of cloves (EAEC) and the potential bioactive components responsible for its antitumor activity. The effects of EAEC on cell growth, cell cycle distribution, and apoptosis were investigated using human cancer cell lines. The molecular changes associated with the effects of EAEC were analyzed by Western blot and (qRT)-PCR analysis. The in vivo effect of EAEC and its bioactive component was investigated using the HT-29 tumor xenograft model. We identified oleanolic acid (OA) as one of the components of EAEC responsible for its antitumor activity. Both EAEC and OA display cytotoxicity against several human cancer cell lines. Interestingly, EAEC was superior to OA and the chemotherapeutic agent 5-fluorouracil at suppressing growth of colon tumor xenografts. EAEC promoted G 0 /G 1 cell cycle arrest and induced apoptosis in a dose-dependent manner. Treatment with EAEC and OA selectively increased protein expression of p21 WAF1/Cip1 and γ-H2AX and downregulated expression of cell cycle-regulated proteins. Moreover, many of these changes were at the mRNA level, suggesting transcriptional regulation by EAEC treatment. Our results demonstrate that clove extract may represent a novel therapeutic herb for the treatment of colorectal cancer, and OA appears to be one of the bioactive components.