Garlic compounds induced calpain and intrinsic caspase cascade for apoptosis in human malignant neuroblastoma SH-SY5Y cells

Abstract

Malignant (N-type) neuroblastoma continues to defy current chemotherapeutic regimens. We tested the garlic compounds diallyl sulfide (DAS) and diallyl disulfide (DADS) for induction of apoptosis in human malignant neuroblastoma SH-SY5Y cells. Viability of human primary neurons was unaffected after 24 h treatment with 50 and 100 microM DAS and 50 microM DADS but slightly affected with 100 microM DADS. Treatment with 50 and 100 microM DAS or DADS significantly decreased viability in SH-SY5Y cells. Wright staining showed morphological features of apoptosis in SH-SY5Y cells treated with 50 and 100 microM DAS or DADS for 24 h. ApopTag assay demonstrated DNA fragmentation in apoptotic cells. Apoptosis was associated with an increase in [Ca(2+)](i), increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, increase in cytosolic Smac/Diablo, and down regulation of inhibitor-of-apoptosis proteins and nuclear factor kappa B (NFkappaB). Activation of caspase-9 and caspase-3 indicated involvement of intrinsic pathway of apoptosis. Calpain and caspase-3 activities produced 145 kD spectrin break down product (SBDP) and 120 kD SBDP, respectively. Also, caspase-3 activity cleaved inhibitor of caspase-activated DNase (ICAD). Results strongly suggested that the garlic compounds DAS and DADS suppressed anti-apoptotic factors and activated calpain and intrinsic caspase cascade for apoptosis in SH-SY5Y cells.

Biological properties of garlic and garlic‐derived organosulfur compounds

“…Moreover, they observed that elevated Ca 21 level caused calpain activation in SH-SY5Y cells [Karmakar et al, 2007]. Calpain is a Ca 21 -dependent noncaspase cysteine protease that can contribute to cell death by inducing the mitochondrial apoptosis pathway independently of caspases.…”

Terpinen-4-ol Induces Autophagic and Apoptotic Cell Death in Human Leukemic HL-60 Cells

“…Ratana Banjerdpongchai*, Patompong Khaw-on chromatin condensation, and membrane blebbing (Karmakar et al, 2007).…”

Potential Health Benefits of Garlic (Allium Sativum): A Narrative Review

“…Numerous epidemiological, clinical and laboratory studies have demonstrated the role of garlic in cancer prevention (Milner 2001, Flieischauer et al 2001, Galeone et al 2006, Setiawan et al 2005 especially in relation to digestive tract cancers, including esophageal and stomach cancers (Gao et al 1999, Berspalov et al 2004. There is also promising research evaluating the use of garlic in leukemic (Hassan), melanoma (Taylor et al 2006) and neuroblastoma (Karmakar et al 2007) cell lines.…”