Effect of Sulforaphane on Growth Inhibition in Human Brain Malignant Glioma GBM 8401 Cells by Means of Mitochondrial- and MEK/ERK-Mediated Apoptosis Pathway
- 615 Downloads
In recent studies, sulforaphane (SFN) has been seen to demonstrate antioxidant and anti-tumor activities as well as potent chemopreventive action against cancer. The present study investigates the anti-proliferation (using MTT assay, SFN demonstrated cytotoxic activity against GBM 8401 cell with IC50 values at 35.52 μM) and induced apoptosis of SFN 24-h treatment in the cells of human brain malignant glioma GBM 8401 cells. We studied the MMP, caspase, MEK/ERK activation, and NF-κB transcription factor activity. Our results indicate that SFN inhibits cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects increased in proportion to the dosage of SFN, and apoptosis was induced via mitochondria- and caspase-dependent pathways. Daily s.c. injections of SFN for 3 weeks in severe combined immunodeficient mice (SCID) with GBM8401 s.c. tumors resulted in a decrease in mean tumor weight of 69–75 % compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, SFN may provide antitumor activity in established malignant glioma.
KeywordsSulforaphane Malignant glioma Mitochondrial MEK/ERK pathway Apoptosis
The authors gratefully acknowledge the financial support from Tainan Sin-Lau Hospital (99-01 and 100-01).
- 1.Mukherjee, S., Bhattacharya, R. K., & Roy, M. (2009). Targeting protein kinase C (PKC) and telomerase by phenethyl isothiocyanate (PEITC) sensitizes PC-3 cells towards chemotherapeutic drug-induced apoptosis. Journal of Environmental Pathology, Toxicology and Oncology, 28(4), 269–282.PubMedGoogle Scholar
- 3.Stan, S. D., Singh, S. V., & Brand, R. E. (2010). Chemoprevention strategies for pancreatic cancer. Nature Reviews Gastroenterology & Hepatology, 7(6), 347–356.Google Scholar
- 35.Kunnumakkara, A. B., Guha, S., Krishnan, S., et al. (2007). Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Research, 67(8), 3853–3861.PubMedCrossRefGoogle Scholar
- 39.Roy, S. K., Srivastava, R. K., & Shankar, S. (2010). Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer. Journal of Molecular Biology, 5, 10.Google Scholar