Differential Pharmacological Activities of Oxygen Numbers on the Sulfoxide Moiety of Wasabi Compound 6-(Methylsulfinyl) Hexyl Isothiocyanate in Human Oral Cancer Cells.

6-(methylsulfinyl) hexyl isothiocyanate (6-MITC) is a naturally occurring compound isolated from Wasabia japonica (wasabi). The synthetic derivatives, 6-(methylsulfenyl) hexyl isothiocyanate (I7447) and 6-(methylsulfonyl) hexyl isothiocyanate (I7557), were derived from 6-MITC with the deletion and addition of oxygen, respectively. We aimed to evaluate the effect of these synthetic compounds on human oral cancer cells, SAS and OECM-1. All three compounds (I7447, 6-MITC, and I7557) inhibited the viability of SAS and OECM-1 cells using MTT assay. Morphological observations showed various proportions of mitotic arrest and apoptosis in cells treated with these compounds. Cell cycle analysis revealed relatively abundant G2/M arrest in 6-MITC and I7557-treated cells, whereas sub-G1 accumulation was found in I7447-treated cells. In using phosphorylated histone H3 as a marker for mitosis, the addition of 6-MITC and I7557 (excluding I7447) could be shown to arrest cells during mitosis. In contrast, I7447 induced more prominent apoptosis than the 6-MITC or I7557 compounds. The down-regulated expression of the phosphorylated form of CHK1 and Cdc25c was noted in 6-MITC and I7557-treated cells. I7557 could sensitize SAS cells to death by radiation. The wasabi compound, 6-MITC, and its chemical derivatives with different numbers of oxygen may have differential pharmacological effects on human oral cancer cells.

Traditional Chinese medicine Danggui Buxue Tang inhibits colorectal cancer growth through induction of autophagic cell death.

PURPOSE: The induction of autophagic cell death is an important process in the development of anticancer therapeutics. We aimed to evaluate the activity of the ancient Chinese decoction Danggui Buxue Tang (DBT) against colorectal cancer (CRC) and the associated autophagy-related mechanism. MATERIALS AND METHODS: CT26 CRC cells were implanted into syngeneic BALB/c mice for the tumor growth assay. DBT extracts and DBT-PD (polysaccharide-depleted) fractions were orally administered. The toxicity profiles of the extracts were analyzed using measurements of body weight, hemogram, and biochemical parameters. The morphology of tissue sections was observed using light and transmission electron microscopy. Western blotting and small interference RNA assays were used to determine the mechanism. RESULTS: DBT-PD and DBT, which contained an equal amount of DBT-PD, inhibited CT26 syngeneic tumor growth. In the tumor specimen, the expression of microtubule-associated proteins 1A/1B light chain 3B (LC3B) was upregulated by DBT-PD and DBT. The development of autophagosomes was observed via transmission electron microscopy in tumors treated with DBT-PD and DBT. In vitro experiments for mechanism clarification demonstrated that DBT-PD could induce autophagic death in CT26 cells accompanied by LC3B lipidation, downregulation of phospho-p70s6k, and upregulation of Atg7. RNA interference of Atg7, but not Atg5, partially reversed the effect of DBT-PD on LC3B lipidation and expression of phospho-p70s6k and Atg7. The changes in ultrastructural morphology and LC3B expression induced by DBT-PD were also partially blocked by the knockdown of Atg7 mRNA. CONCLUSION: DBT induced autophagic death of colorectal cancer cells through the upregulation of Atg7 and modulation of the mTOR/p70s6k signaling pathway.

The Traditional Chinese Medicine DangguiBuxue Tang Sensitizes Colorectal Cancer Cells to Chemoradiotherapy.

Chemotherapy is an important treatment modality for colon cancer, and concurrent chemoradiation therapy (CCRT) is the preferred treatment route for patients with stage II and III rectal cancer. We examined whether DangguiBuxue Tang (DBT), a traditional Chinese herbal extract, sensitizes colorectal cancer cells to anticancer treatments. The polysaccharide-depleted fraction of DBT (DBT-PD) contains greater amounts of astragaloside IV (312.626 µg/g) and ferulic acid (1.404 µg/g) than does the original formula. Treatment of the murine colon carcinoma cell line (CT26) with DBT-PD inhibits growth, whereas treatment with comparable amounts of purified astragaloside IV and ferulic acid showed no significant effect. Concurrent treatment with DBT-PD increases the growth inhibitory effect of 5-fluorouracil up to 4.39-fold. DBT-PD enhances the effect of radiation therapy (RT) with a sensitizer enhancement ratio (SER) of up to 1.3. It also increases the therapeutic effect of CCRT on CT26 cells. Cells treated with DBP-PD showed ultrastructural changes characteristic of autophagy, including multiple cytoplasmic vacuoles with double-layered membranes, vacuoles containing remnants of degraded organelles, marked swelling and vacuolization of mitochondria, and autolysosome-like vacuoles. We conclude that DBT-PD induces autophagy-associated cell death in CT26 cells, and may have potential as a chemotherapy or radiotherapy sensitizer in colorectal cancer treatment.

Armillaridin, a Honey Medicinal Mushroom, Armillaria mellea (Higher Basidiomycetes) Component, Inhibits Differentiation and Activation of Human Macrophages.

Armillaridin (AM) is an aromatic ester compound isolated from honey medicinal mushroom, Armillaria mellea, which has anti-cancer potential. This study was designed to examine the effects of AM on differentiation and activation macrophages, the major ontogeny of innate immunity. Macrophages were derived from CD14+ monocytes which were sorted from human peripheral blood mononuclear cells. Cell viability was assessed by trypan blue exclusion test. Cells were stained with Liu's dye for observation of morphology. Expression of surface antigens was examined by flow cytometric analysis. Phagocytosis and generation of reactive oxygen species (ROS), as functional assays, were evaluated by counting engulfed yeasts and DCFH-DA reaction. The viability of macrophages was not significantly reduced by AM. AM at nontoxic concentrations markedly increased cytoplasmic vacuoles. The expression of surface CD14, CD16, CD36, and HLA-DR was suppressed. The phagocytosis function, but not ROS production, of macrophages was inhibited by AM. Armillaridin could inhibit the differentiation and activation of human macrophages. It may have potential to be developed as a biological response modifier for inflammatory diseases.