The in vivo antitumor effects on human COLO 205 cancer cells of the 4,7-dimethoxy-5-(2-propen-1-yl)-1,3-benzodioxole (apiole) derivative of 5-substituted 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1) isolated from the fruiting body of Antrodia camphorate.
BACKGROUND
The compound 4,7-dimethoxy-5-(2-propen-1-yl)-1,3-benzodioxole (apiole) has been isolated from several different plant species, including Petroselinum sativum. Our recent study found that apiole is a chemical derivative of 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1), which has been isolated from dried Antrodia camphorata (AC ) fruiting bodies, a traditional Chinese medicine with antitumor properties.


OBJECTIVE
Our previous in vitro study demonstrated that apiole inhibits the growth of human colon (COLO 205) cancer cells through the arrest of the cell cycle in G0/G1 phase. The in vivo antitumor effects of apiole were evaluated in this study.


METHODS
Apiole was administered to mice at 1-30 mg/kg body weight through intraperitoneal (I.P.) injection three times per week (defined as a dosage of 1×-30×).


METHODS
The in vivo antitumor effects of apiole were evaluated in mice with xenografts of COLO 205 cells.


METHODS
All of the data are reported as the means ± S.E. Comparisons were performed with a one-way analysis of variance (ANOVA) followed by a Fisher's least significant difference test. Significance was defined as P < 0.05.


RESULTS
Apiole (> 1×) markedly decreased the growth of COLO 205 human colon cancer cell tumor xenografts in an athymic nude mouse model system through the up-regulation of cell cycle regulators, such as p53, p21/Cip1, and p27/Kip1. The apiole-induced increase in G0/G1 phase cell cycle regulators was also associated with a significant decrease in the expression of cyclins D1 and D3. Surprisingly, statistically significantly higher tumor volumes were observed in mice that received 5× apiole compared with 30× apiole-treated mice (P < 0.05). No gross signs of toxicity were observed (e.g., body weight changes, general appearance, or individual organ effects) in any group.


CONCLUSIONS
Our results show, for the first time, the promising antitumor effects of apiole against colon tumors in an in vivo xenograft model.
Department of Surgery, School of Medicine, Taipei Medical University, Taipei, Taiwan.
Po-Li
PL
Wei
Shih-Hsin
SH
Tu
Hsiu-Man
HM
Lien
Li-Ching
LC
Chen
Ching-Shyang
CS
Chen
Chih-Hsiung
CH
Wu
Ching-Shui
CS
Huang
Hui-Wen
HW
Chang
Chien-Hsi
CH
Chang
How
H
Tseng
Yuan-Soon
YS
Ho
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D055491:Antrodia / Q000737:chemistry*; D052117:Benzodioxoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D004149:Dioxoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D048690:Fruiting Bodies, Fungal / Q000737:chemistry*; D006801:Humans; D051379:Mice; D023041:Xenograft Model Antitumor Assays; D000081248:Allylbenzene Derivatives
D000972:Antineoplastic Agents, Phytogenic; D052117:Benzodioxoles; D018797:Cell Cycle Proteins; D004149:Dioxoles; C446539:apiole; D000081248:Allylbenzene Derivatives