trans-4,4’-Dihydroxystilbene (DHS) inhibits human neuroblastoma tumor growth and induces mitochondrial and lysosomal damages in neuroblastoma cell lines

SH-SY5Y MTT assay Clonogenic assay
DOI: 10.18632/oncotarget.17879 Publication Date: 2017-05-16T10:25:17Z
ABSTRACT
// Bhaskar Saha 1, 2, * , Birija Sankar Patro 3, 4, Mrunesh Koli 3 Ganesh Pai Jharna Ray 2 Sandip K. Bandyopadhyay 1 and Subrata Chattopadhyay 4 Vijaygarh Jyotish College, Jadavpur, Kolkata 700 032, India S. N. Pradhan Centre for Neuroscience, Ballygunge Science University of Calcutta, 019, Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400085, Homi National Institute, Training School Complex, Anushakti Nagar, 400094, These authors have contributed equally to this work Correspondence to: Chattopadhyay, email: schatt@barc.gov.in Keywords: apoptosis, trans -4,4'-dihydroxystilbene, neuroblastoma, lysosomal membrane permeabilization, mitochondrial permeabilization Received: September 09, 2016 Accepted: March 24, 2017 Published: May 16, ABSTRACT In view the inadequacy neuroblastoma treatment, five hydroxystilbenes resveratrol (Resv) were screened their cytotoxic property against human cell lines. The mechanism action most potent compound, -4,4'-dihydroxystilbene (DHS) was investigated in vitro using DHS also tested a mouse xenograft model tumor. MTT, sub-G1, annexin V clonogenic assays as well microscopy established higher cytotoxicity than Resv IMR32 line. (20 μM) induced (MMP) cells, revealed from JC-1 staining, cytochrome c ApaF1 release caspases-9/3 activation. (LMP) cathepsins B, L D, inhibitors partially reduced MMP/caspase-3 ROS, produced by activated p38 JNK MAPKs augment BAX activity BID-cleavage, induce LMP MMP cells. (100 mg/kg) inhibited tumor growth SCID mice 51%. Hence, may be potential chemotherapeutic option neuroblastoma. involvement an independent LMP-dependent is attractive it provides options target both mitochondria lysosome.
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