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

Oncotarget
Bhaskar SahaSubrata Chattopadhyay

Abstract

In view of the inadequacy of neuroblastoma treatment, five hydroxystilbenes and resveratrol (Resv) were screened for their cytotoxic property against human neuroblastoma cell lines. The mechanism of cytotoxic action of the most potent compound, trans-4,4'-dihydroxystilbene (DHS) was investigated in vitro using human neuroblastoma cell lines. DHS was also tested in a mouse xenograft model of human neuroblastoma tumor. The MTT, sub-G1, annexin V and clonogenic assays as well as microscopy established higher cytotoxicity of DHS than Resv to the IMR32 cell line. DHS (20 μM) induced mitochondrial membrane permeabilization (MMP) in the cells, as revealed from JC-1 staining, cytochrome c and ApaF1 release and caspases-9/3 activation. DHS also induced lysosomal membrane permeabilization (LMP) to release cathepsins B, L and D, and the cathepsins inhibitors partially reduced MMP/caspase-3 activation. The ROS, produced by DHS activated the p38 and JNK MAPKs to augment the BAX activity and BID-cleavage, and induce LMP and MMP in the cells. DHS (100 mg/kg) also inhibited human neuroblastoma tumor growth in SCID mice by 51%. Hence, DHS may be a potential chemotherapeutic option against neuroblastoma. The involvement of an independent LMP as ...Continue Reading

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Citations

Nov 8, 2017·Nutrients·Waqas NawazXiaohong Shu
Mar 16, 2019·Beilstein Journal of Organic Chemistry·Seema V KanojiaDibakar Goswami
Sep 14, 2020·Reviews in the Neurosciences·Kamil LeisPrzemysław Gałązka
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Feb 3, 2021·Journal of Medicinal Chemistry·Saikat ChakrabortyBirija Sankar Patro
Jan 1, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Verica PaunovicLjubica Harhaji-Trajkovic
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Bhaskar SahaSubrata Chattopadhyay

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Methods Mentioned

BETA
xenograft
flow cytometry
fluorescence microscopy
transfection
xenografts

Software Mentioned

Kodak Gel - doc
FlowJo

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