Korean J Physiol Pharmacol.  2012 Oct;16(5):321-326. 10.4196/kjpp.2012.16.5.321.

Antiproliferative and Cytotoxic Effects of Resveratrol in Mitochondria-Mediated Apoptosis in Rat B103 Neuroblastoma Cells

• Rahman MA
• Kim NH
• Kim SH
• Oh SM
• Huh SO

• KMID: 1493964
• DOI: http://doi.org/10.4196/kjpp.2012.16.5.321

Abstract

Resveratrol, a natural compound, has been shown to possess anti-cancer, anti-aging, anti-inflammatory, anti-microbial, and neuroprotective activities. In this study, we examined the antiproliferative and cytotoxicity properties of resveratrol in Rat B103 neuroblastoma cells; although it's molecular mechanisms for the biological effects are not fully defined. Here, we examined the cellular cytotoxicity of resveratrol by cell viability assay, antiproliferation by BrdU assay, DNA fragmentation by DNA ladder assay, activation of caspases and Bcl-2 family proteins were detected by western blot analyses. The results of our investigation suggest that resveratrol increased cellular cytotoxicity of Rat B103 neuroblastoma cells in a dose-and time-dependent manner with IC50 of 17.86 microM at 48 h. On the other hand, incubation of neuroblastoma cells with resveratrol resulted in S-phase cell cycle arrests which dose-dependently and significantly reduced BrdU positive cells through the downregulation of cyclin D1 protein. In addition, resveratrol dose-dependently and significantly downregulated the expression of anti-apoptotic protein includes Bcl-2, Bcl-xL and Mcl-1 and also activates cleavage caspase-9 and-3 via the downregulation of procaspase-9 and -3 in a dose-dependent manner which indicates that involvement of intrinsic mitochondria-mediated apoptotic pathway. In conclusion, resveratrol increases cellular cytotoxicity and inhibits the proliferation of B103 neuroblastoma cells by inducing mitochondria-mediated intrinsic caspase dependent pathway which suggests this natural compound could be used as therapeutic purposes for neuroblastoma malignancies.

Keyword

Apoptosis; Bcl-2 family; Cyclin D1; Neuroblastoma; Resveratrol

MeSH Terms

Animals
Apoptosis
Blotting, Western
Bromodeoxyuridine
Caspase 9
Caspases
Cell Cycle Checkpoints
Cell Survival
Cyclin D1
DNA
DNA Fragmentation
Down-Regulation
Hand
Humans
Inhibitory Concentration 50
Neuroblastoma
Proteins
Rats
Stilbenes
Bromodeoxyuridine
Caspase 9
Caspases
Cyclin D1
DNA
Proteins
Stilbenes

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