In:
Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 5, No. 11_Supplement ( 2012-11-01), p. A75-A75
Abstract:
It is now well accepted that natural compounds provide the opportunity to interfere in early stages of cancer or prevent its development altogether. However, these types of compounds do have their limitations, such as short half-life and fast metabolism once ingested. Often, presence of the compound can only be assessed by quantification of metabolites, suggesting that these metabolites circulate in the body for a certain amount of time and potentially interact with biological processes. In the present study, we investigated the biotransformation of [6]-shogaol, a bioactive component in ginger (Zingiber officinale Rosc.), in cancer cells, mice and humans. Our results indicated that [6] -shogaol is extensively metabolized in cancer cells and in vivo. To further investigate whether these metabolites retain bioactivity, we synthesized the major metabolites of [6]-shogaol and evaluate their anti-cancer activities. Twelve metabolites of [6] -shogaol (M1, M2, and M4-M13) were successfully synthesized using simple and easily accessible chemical methods. Growth inhibition assays showed most metabolites of [6]-shogaol had measurable activities against human cancer cells HCT-116 and H-1299. In particular, metabolite M2 greatly retained the biological activities of [6] -shogaol. The toxicity evaluation of the synthetic metabolites (M1, M2, and M4-M13) against human normal fibroblast colon cells CCD-18Co and human normal lung cells IMR-90 demonstrated a detoxifying metabolic biotransformation of [6]-shogaol. The most active metabolite M2 had almost no toxicity to CCD-18Co and IMR-90 normal cells. TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay indicated apoptosis was triggered by metabolites M2, M13, and its two diastereomers M13-1 and M13-2. There was no significant difference between the apoptotic effect of [6] -shogaol and those of M2 and M13 at 6 hour time point treatment. (This project is supported by NIH grants CA138277 and CA138277-S1 to S. Sang). Citation Format: Huadong Chen, Yingdong Zhu, Dominique Soroka, Renaud Warin, Shengmin Sang. Metabolites of ginger component [6]-shogaol remain bioactive in cancer cells and have low toxicity in normal cells: Biotransformation, chemical synthesis, and biological evaluation. [abstract] . In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A75.
Type of Medium:
Online Resource
ISSN:
1940-6207
,
1940-6215
DOI:
10.1158/1940-6207.PREV-12-A75
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2422346-3
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