Science of Ashwagandha: Preventive and Therapeutic Potentials by Sunil C. Kaul & Renu Wadhwa

Author:Sunil C. Kaul & Renu Wadhwa
Language: eng
Format: epub, pdf
Publisher: Springer International Publishing, Cham

12.6.5 Mortalin

Mortalin/GPR75/heat sock protein (HSP70)/cytosolic heat shock protein is a ubiquitous mitochondrial chaperone and plays an important role in human carcinogenesis by increasing cancer cell proliferation, protection of cancer cells against apoptosis (Saxena et al. 2013; Lu et al. 2011a; Wadhwa et al. 2006). It interacts with tumor suppressor protein p53 and inactivates its functions including transcriptional activation and control of centrosome duplication leading to uncontrolled proliferation, a hallmark of cancer cell (Wadhwa et al. 1998; Lu et al. 2011a, b). Most recently, it was shown to activate telomerase and hnRNP-K proteins and contribute to malignant phenotype of cancer cells (Gao et al. 2013). In agreement with these reports, knockdown of mortalin in cancer cells was shown to activate p53 function and cause their growth arrest or apoptosis (Nigam et al. 2015; Lu et al. 2011b). Some studies have shown correlation of mortalin expression level with metastatic potential and tumor recurrence in case of hepatocellular carcinoma, suggesting clinical application of mortalin as a chemotherapeutic drug target (Lu et al. 2011a). Chen et al also showed that the genetically isogenic cell lines with variable metastatic potentials possess tight correlation with the level of expression of mortalin, suggesting its role in metastatic hepatocellular carcinoma (HCC) (Chen et al. 2011). Furthermore, mortalin-compromised cells showed inhibition of EMT suggesting mortalin as a therapeutic target for HCC metastasis. Ashwagandha withanolide, Withanone was shown to binds with mortalin, like MKT-077 (mortalin inhibitor) at the Phe 272 and Asn 139 (lactone group in withanone) (Grover et al. 2012a). It resulted in abrogation of mortalin-p53 complexes and reactivation of p53 proteins leading to growth arrest of cancer cells (Wadhwa et al. 2016).

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