Nikhil Hebbar

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Tumor suppressor PAR-4 acts in part by modulating sensitivity to apoptosis, but the basis for its activity is not fully understood. In this study, we describe a novel mechanism of antiapoptosis by NF-κB, revealing that it can block PAR-4-mediated apoptosis by downregulating trafficking of the PAR-4 receptor GRP78 from the endoplasmic reticulum to the cell(More)
The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This(More)
The tumor suppressor protein prostate apoptosis response-4 (Par-4), which is secreted by normal cells, selectively induces apoptosis in cancer cells. We identified a 3-arylquinoline derivative, designated Arylquin 1, as a potent Par-4 secretagogue in cell cultures and mice. Mechanistically, Arylquin 1 binds vimentin, displaces Par-4 from vimentin for(More)
Par-4 is a pro-apoptotic, tumor suppressor protein that induces apoptosis selectively in cancer cells. Endoplasmic reticulum-stress and higher levels of protein kinase A in tumor cells confer the coveted feature of cancer selective response to extracellular and intracellular Par-4, respectively. Recent studies have shown that systemic Par-4 confers(More)
Tumor suppressor genes play an important role in preventing neoplastic transformation and maintaining normal tissue homeostasis. Par-4 is one such tumor suppressor which is unique in its ability to selectively induce apoptosis in cancer cells while leaving the normal cells unaffected. The cancer cell specific activity of Par-4 is elicited through(More)
Therapy resistance and disease recurrence are two of the most challenging aspects in breast cancer treatment. A recent article in Cancer Cell makes a significant contribution toward a better understanding of this therapeutic problem by establishing downregulation of the tumor suppressor Par-4 as the primary determinant of breast cancer recurrence. This(More)
Tripti Shrestha-Bhattarai,1,5 Nikhil Hebbar,1,5 and Vivek M. Rangnekar1,2,3,4,* 1Graduate Center for Toxicology 2Department of Radiation Medicine 3Department of Microbiology, Immunology and Molecular Genetics 4L.P. Markey Cancer Center University of Kentucky, Lexington, KY 40508, USA 5These authors contributed equally to this work *Correspondence:(More)
Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a prostate apoptosis response-4 (Par-4) amino-terminal fragment (PAF)(More)