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.

Abstract

CONTEXT:

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.

AIMS:

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.

SETTING AND DESIGN:

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×).

MATERIALS AND METHODS:

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

STATISTICAL ANALYSIS:

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.

• Authors: Po-Li Wei, Shih-Hsin Tu, Hsiu-Man Lien, Li-Ching Chen, Ching-Shyang Chen, Chih-Hsiung Wu, Ching-Shui Huang, Hui-Wen Chang, Chien-Hsi Chang, How Tseng, Yuan-Soon Ho
• Journal: Journal of cancer research and therapeutics (J Cancer Res Ther) 2012 Oct-Dec Vol. 8 Issue 4 Pg. 532-6 ISSN: 1998-4138 [Electronic] India
• PMID: 23361270 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Benzodioxoles
• Cell Cycle Proteins
• Dioxoles
• apiole

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, chemistry, pharmacology)
• Antrodia (chemistry)
• Benzodioxoles (administration & dosage, chemistry, pharmacology)
• Body Weight (drug effects)
• Cell Cycle (drug effects)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, genetics, metabolism)
• Dioxoles (administration & dosage, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Female
• Fruiting Bodies, Fungal (chemistry)
• Humans
• Mice
• Xenograft Model Antitumor Assays