Multifaceted cytoprotection by synthetic polyacetylenes inspired by the ginseng-derived natural product, panaxytriol Journal Article
| Authors: | Chou, T. C.; Dong, H.; Zhang, X.; Lei, X.; Hartung, J.; Zhang, Y.; Lee, J. H.; Wilson, R. M.; Danishefsky, S. J. |
| Article Title: | Multifaceted cytoprotection by synthetic polyacetylenes inspired by the ginseng-derived natural product, panaxytriol |
| Abstract: | We describe herein the discovery of a series of panaxytriol (PXT)-derived polyacetylene small molecules with promising cytoprotective activity. In mouse xenograft models, we have demonstrated the capacity of our synthetic analogs to mitigate a range of cancer therapeutic agent-induced toxicities, including body weight loss, lethality, neurotoxicity, and hematotoxicity. Our PXT analogs have also been found to reduce radiation-induced body weight loss and lethality in mouse models. Moreover, several PXT analogs appear to exhibit moderate in vivo antiinflammatory activity as well as in vitro immunoenhancing capabilities. These compounds appear to derive their activity through induction of cancer preventive phase 2 enzymes. The studies described herein suggest that coadministration of a PXT-derived agent with cancer chemotherapeutics or radiation therapy may serve to mitigate a range of therapy-associated toxicities. |
| Keywords: | cancer chemotherapy; controlled study; unclassified drug; human cell; fluorouracil; nonhuman; paclitaxel; cancer radiotherapy; neurotoxicity; antineoplastic agent; mouse; animals; mice; cell death; cancer prevention; blood toxicity; animal experiment; animal model; weight loss; weight reduction; cyclophosphamide; vincristine; in vivo study; cytotoxicity; in vitro study; tumor xenograft; xenograft model antitumor assays; radiation exposure; cancer inhibition; cancer regression; mice, nude; longevity; antiinflammatory activity; cell protection; isofludelone; biological products; lethality; epothilone derivative; cytoprotection; x-rays; chemoprotective; neutraceutical; panaxytriol; panaxytriol acetonide; polyacetylene derivative; ginseng; isomerism; panax ginseng; enediynes; fatty alcohols; panax; polyacetylenes |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 108 |
| Issue: | 34 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2011-08-23 |
| Start Page: | 14336 |
| End Page: | 14341 |
| Language: | English |
| DOI: | 10.1073/pnas.1111332108 |
| PROVIDER: | scopus |
| PMCID: | PMC3161558 |
| PUBMED: | 21844359 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 October 2011" - "CODEN: PNASA" - "Source: Scopus" |
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