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Withanolide A Extends the Lifespan in Human EGFR-driven Cancerous Caenorhabditis Elegans

Withanolide A Extends the Lifespan in Human EGFR-driven Cancerous Caenorhabditis Elegans

Bashir Akhlaq Akhoon, Laxmi Rathor, Rakesh Pandey

Exp Gerontol. 2018 Apr;104:113-117.

PMID: 29427754

Abstract:

The conserved EGFR pathway is linked with multiple cancers in humans including breast, ovarian, and lung carcinoma. Withanolide A, one of the major withanolidal active compounds isolated from the Withania somnifera, extends lifespan and ameliorates stress resistance in wild-type C. elegans by targeting the Insulin/IGF-1 signaling pathway. Up-regulation of IGF1 can transactivate EGFR which inturn reduces longevity and promotes tumor development in an organism. We examined the effects of Withanolide A on the lifespan of a human EGFR-driven C. elegans transgenic model exhibiting the multivulva (Muv) phenotype. The results showed that WA extends the lifespan of both wild human EGFR-driven C. elegans model (human wild-type tyrosine kinase) as well as models bearing single (L858R), and double mutations (T790M-L858R). The lifespan extension observed in these transgenic strains was 20.35, 24.21 and 21.27%, respectively. Moreover, the reduced fat levels were noticed in both wild-type N2 worms and transgenic strains. These observations support the heathspan promoting effect of WA as lipid-rich diet has been reported to promote tumor development. In view of the fact that most of the well known FDA approved drugs such as gefitinib fail to inhibit the EGFR-associated cancers because of these mutations, the present findings show the potential of Withanolide A as a foreseen future nutraceutical to improve the average survival of cancer patients.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP32911629	Withanolide A		32911-62-9	Price
IAR42413242	EGFR (L858R) Active human			Price

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