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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.

Curcumin encapsulated in mesoporous silica nanoparticles 5 showed improved solubility, in vitro release profile and significantly enhanced cell cytotoxicity compared to the pure drug. Curcumin, a diferuloylmethane obtained from the rhizomes of the plant Curcuma longa, 1 is commonly used as a spice, dye and 10 traditional medicine in Indian and Chinese culture (see Scheme 1A for its structure). Curcumin possesses a range of pharmacological activities such as antiseptic, anti-inflammatory, antioxidant, antiarthritic, and anticancer functions. 2 It has been found that curcumin inhibits the viability and proliferation in a 15 variety of human cancer cell lines including gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, lung cancer, melanoma, and sarcoma. 3, 4 Despite of its advantages, the clinical application of curcumin is stalled due to its poor aqueous solubility leading to poor bioavailability. 5 20 65

BACKGROUND. Glioblastoma, which is the most malignant brain tumor, remains incurable and almost always causes death. As a new treatment strategy, the combination of all‐trans retinoic acid (ATRA) and paclitaxel was explored for controlling the growth of glioblastoma U87MG xenografts. METHODS. Human glioblastoma U87MG xenografts were developed in athymic nude mice for treatments with ATRA, paclitaxel, and ATRA plus paclitaxel. The efficacy of treatments in controlling tumor growth was assessed by histologic examination, Western blot analysis, and immunofluorescent labelings. RESULTS. Astrocytic differentiation in U87MG xenografts was associated with increased GFAP expression and decreased telomerase expression. The combination of ATRA and paclitaxel was found to cause more apoptosis than paclitaxel alone. Apoptosis occurred with down‐regulation of MEK‐2 and overexpression of p‐ERK, p‐JNK, and p‐p38 MAPK. Down‐regulation of both Akt and p‐Akt also favored the apoptotic process. Combination therapy activated the receptor‐mediated pathway of apoptosis with induction of TNF‐α, activation of caspase‐8, and cleavage of Bid to tBid. Combination therapy also induced the mitochondria‐mediated pathway of apoptosis with an increase in the Bax:Bcl‐2 ratio and mitochondrial release of cytochrome c and Smac/Diablo into the cytosol. In addition, combination therapy promoted phosphorylation of Bcl‐2 for its inactivation and down‐regulated NF‐κB and BIRC proteins, indicating suppression of several cell survival factors. Western blot analysis demonstrated that activation of cysteine proteases such as calpain, caspase‐12, caspase‐9, and caspase‐3 contributed to apoptosis. Immunofluorescent labelings confirmed overexpression of cysteine proteases in apoptosis. CONCLUSIONS. Treatment of U87MG xenografts with a combination of ATRA and paclitaxel induced differentiation and also multiple molecular mechanisms for apoptosis. Cancer 2008. © 2007 American Cancer Society.