Secretory prostate apoptosis response (Par)-4 sensitizes multicellular spheroids (MCS) of glioblastoma multiforme cells to tamoxifen-induced cell death

Publication date: Available online 21 November 2014 Source:FEBS Open Bio Author(s): Jayashree C. Jagtap , Parveen D , Reecha D. Shah , Aarti Desai , Dipali Bhosale , Ashish Chugh , Deepak Ranade , Swapnil Karnik , Bhushan Khedkar , Aaishwarya Mathur , Kumar Natesh , Goparaju Chandrika , Padma Shastry Glioblastoma multiforme (GBM) is the most malignant form of brain tumor and is associated with resistance to conventional therapy and poor patient survival. Prostate apoptosis response (Par)-4, a tumor suppressor, is expressed as both an intracellular and secretory/extracellular protein. Though secretory Par-4 induces apoptosis in cancer cells, its potential in drug-resistant tumors remains to be fully explored. Multicellular spheroids (MCS) of cancer cells often acquire multi-drug resistance and serve as ideal experimental models. We investigated the role of Par-4 in Tamoxifen (TAM)-induced cell death in MCS of human cell lines and primary cultures of GBM tumors. TCGA and REMBRANT data analysis revealed that low levels of Par-4 correlated with low survival period (21.85±19.30 days) in GBM but not in astrocytomas (59.13±47.26 days) and oligodendrogliomas (58.04± 59.80 days) suggesting low PAWR expression as a predictive risk factor in GBM. Consistently, MCS of human cell lines and primary cultures displayed low Par-4 expression, high level of chemo-resistance genes and were resistant to TAM-induced cytotoxicity. In monolayer cells, TAM-induced cytotoxicity was...
Source: FEBS Open Bio - Category: Molecular Biology Source Type: research