Corrigendum to "Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/ß-Catenin Signaling and Apoptosis Induction".

[This corrects the article DOI: 10.1155/2013/146136.].

Honokiol inhibits sphere formation and xenograft growth of oral cancer side population cells accompanied with JAK/STAT signaling pathway suppression and apoptosis induction.

BACKGROUND: Eliminating cancer stem cells (CSCs) has been suggested for prevention of tumor recurrence and metastasis. Honokiol, an active compound of Magnolia officinalis, had been proposed to be a potential candidate drug for cancer treatment. We explored its effects on the elimination of oral CSCs both in vitro and in vivo. METHODS: By using the Hoechst side population (SP) technique, CSCs-like SP cells were isolated from human oral squamous cell carcinoma (OSCC) cell lines, SAS and OECM-1. Effects of honokiol on the apoptosis and signaling pathways of SP-derived spheres were examined by Annexin V/Propidium iodide staining and Western blotting, respectively. The in vivo effectiveness was examined by xenograft mouse model and immunohistochemical tissue staining. RESULTS: The SP cells possessed higher stemness marker expression (ABCG2, Ep-CAM, Oct-4 and Nestin), clonogenicity, sphere formation capacity as well as tumorigenicity when compared to the parental cells. Treatment of these SP-derived spheres with honokiol resulted in apoptosis induction via Bax/Bcl-2 and caspase-3-dependent pathway. This apoptosis induction was associated with marked suppression of JAK2/STAT3, Akt and Erk signaling pathways in honokiol-treated SAS spheres. Consistent with its effect on JAK2/STAT3 suppression, honokiol also markedly inhibited IL-6-mediated migration of SAS cells. Accordingly, honokiol dose-dependently inhibited the growth of SAS SP xenograft and markedly reduced the immunohistochemical staining of PCNA and endothelial marker CD31 in the xenograft tumor. CONCLUSIONS: Honokiol suppressed the sphere formation and xenograft growth of oral CSC-like cells in association with apoptosis induction and inhibition of survival/proliferation signaling pathways as well as angiogenesis. These results suggest its potential as an integrative medicine for combating oral cancer through targeting on CSCs.

Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/ ß -Catenin Signaling and Apoptosis Induction.

Honokiol, an active compound of Magnolia officinalis, exerted many anticancer effects on various types of cancer cells. We explored its effects on the elimination of cancer stem-like side population (SP) cells in human oral squamous cell carcinoma SAS cells. The sorted SP cells possessed much higher expression of stemness genes, such as ABCG2, ABCC5, EpCAM, OCT-4, CD133, CD44, and ß -catenin, and more clonogenicity as compared with the Non-SP cells. After 48 h of treatment, honokiol dose dependently reduced the proportion of SP from 2.53% to 0.09%. Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2. Mechanistically, honokiol inhibited the CD44 and Wnt/ ß -catenin signaling of SP cells. The Wnt signaling transducers such as ß -catenin and TCF-4 were decreased in honokiol-treated SP cells, while the ß -catenin degradation promoting kinase GSK-3 α / ß was increased. Consistently, the protein levels of ß -catenin downstream targets such as c-Myc and Cyclin D1 were also downregulated. Furthermore, the ß -catenin-related EMT markers such as Slug and Snail were markedly suppressed by honokiol. Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/ ß -catenin signaling, and inhibition of EMT.

Elimination of cancer stem-like "side population" cells in hepatoma cell lines by chinese herbal mixture "tien-hsien liquid".

There are increasing pieces of evidence suggesting that the recurrence of cancer may result from a small subpopulation of cancer stem cells, which are resistant to the conventional chemotherapy and radiotherapy. We investigated the effects of Chinese herbal mixture Tien-Hsien Liquid (THL) on the cancer stem-like side population (SP) cells isolated from human hepatoma cells. After sorting and subsequent culture, the SP cells from Huh7 hepatoma cells appear to have higher clonogenicity and mRNA expressions of stemness genes such as SMO, ABCG2, CD133, ß-catenin, and Oct-4 than those of non-SP cells. At dose of 2 mg/mL, THL reduced the proportion of SP cells in HepG2, Hep3B, and Huh7 cells from 1.33% to 0.49%, 1.55% to 0.43%, and 1.69% to 0.27%, respectively. The viability and colony formation of Huh7 SP cells were effectively suppressed by THL dose-dependently, accompanied with the inhibition of stemness genes, e.g., ABCG2, CD133, and SMO. The tumorigenicity of THL-treated Huh7 SP cells in NOD/SCID mice was also diminished. Moreover, combination with THL could synergize the effect of doxorubicin against Huh7 SP cells. Our data indicate that THL may act as a cancer stem cell targeting therapeutics and be regarded as complementary and integrative medicine in the treatment of hepatoma.

Effect of diallyl trisulfide-rich garlic oil on blood coagulation and plasma activity of anticoagulation factors in rats.

Diallyl trisulfide (DAT)-rich garlic oil was fed to Sprague-Dawley rats and the effects of this DAT-rich garlic oil on bleeding time, clotting time and anticoagulation factors were examined. Garlic oil supplement at 5 or 50mg garlic oil/kg bodyweight significantly prolonged bleeding time and thrombin time, and enhanced anticoagulation factor activity, such as antithrombin III and protein C (P<0.05). These results suggested that the anticoagulant action of DAT-rich garlic oil was due to inhibition and/or inactivation of thrombin. In addition, DAT-rich garlic oil benefits blood anticoagulation factors, which might further prevent the development of thrombus formation. However, the intake of garlic oil at high dose significantly increased plasma fibrinogen concentration (P<0.05), and affected the levels of several hematological parameters such as erythrocyte count, hemoglobin and platelets (P<0.05). The adverse effect of high doses of garlic oil might further influence the hemostatic balance. Therefore, the concentration of DAT-rich garlic oil should be carefully considered in its application. Supplementation of garlic oil at 5mg/kg bodyweight has anticoagulation effect in this animal study.