Sulforaphane Decrease of SERTAD1 Expression Triggers G1/S Arrest in Breast Cancer Cells.

Studies have identified the potential of chemopreventive effects of sulforaphane (SFN); however, the underlying mechanisms of its effect on breast cancer require further elucidation. This study investigated the anticancer effects of SFN that specifically induces G1/S arrest in breast ductal carcinoma (ZR-75-1) cells. The proliferation of the cancer cells after treatment with SFN was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DNA content and cell cycle status were analyzed through flow cytometry. Our results demonstrated the inhibition of growth in ZR-75-1 cells upon SFN exposure. In addition, SERTAD1 (SEI-1) caused the accumulation of SFN-treated G1/S-phase cells. The downregulation of SEI-1, cyclin D2, and histone deacetylase 3 suggested that in addition to the identified effects of SFN against breast cancer prevention, it may also exert antitumor activities in established breast cancer cells. In conclusion, SFN can inhibit growth of and induce cell cycle arrest in cancer cells, suggesting its potential role as an anticancer agent.

Induction of Mitotic Delay in Pharyngeal and Nasopharyngeal Carcinoma Cells Using an Aqueous Extract of Ajuga bracteosa.

Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, for which radiotherapy and/or chemotherapy are the primary treatment methods. Many herbs are known to have potential uses in chemotherapy; however, the mechanisms underlying the observed antitumor activity of Ajuga bracteosa (AB) against NPC remain unclear. We explored the antitumor effects of AB, which was shown specifically to induce mitotic delay in pharyngeal (Detroit 562) and nasopharyngeal (Hone-1) cancer cells. Proliferation of cancer cells after exposure to aqueous extract of A. bracteosa (AEAB) was assessed using the MTT assay. DNA content and cell cycle arrest induction were analyzed using flow cytometry. The expression of checkpoint kinase 2 (CHK2), cell division control protein 2 (CDC2), and cyclin B1 was investigated using qRT-PCR and Western blot analysis. Results indicated the inhibition of cancer cell growth following exposure to AEAB. In addition, AEAB induced the accumulation of G2/M-phase cells in cancer cell through the disassociation of CDC2/cyclin B1 complex. Our findings suggested that, in addition to the known effects of AEAB in NPC prevention, it may have antitumor activities against NPC cells. In conclusion, AEAB inhibits the growth of and induces mitotic delay in cancer cells, supporting its use as an anticancer agent.

Induction of Apoptosis in Endometrial Cancer (Ishikawa) Cells by Pogostemon cablin Aqueous Extract (PCAE).

Pogostemon cablin (PC) is a traditional herbal medicine used in the treatment of the common cold, nausea, diarrhea, and even for headaches and fever. However, the mechanisms underlying the anti-proliferative activity of PC in endometrial cancer (EC) cells have yet to be fully elucidated. This study investigated the anticancer effects of an aqueous extract of Pogostemon cablin (PCAE), specifically induced apoptosis in EC (Ishikawa) cells. Proliferation of EC cells following exposure to PCAE was assessed by an MTT assay. DNA content and the induction of cell cycle apoptosis were analyzed by flow cytometry (FACS Calibur). Protein caspase-3 and, -9 as well as AIF were investigated using Western blot. Our results demonstrate growth inhibition of Ishikawa cells by PCAE. Furthermore, caspase-3 activity caused PCAE-treated cell lines to accumulate in apoptosis. Gene expression profiling (GEP) results further suggest that, in addition to its known effects with regard to EC prevention, PCAE may also exert antitumor activity on established EC cells. Many previous studies have identified the chemo-preventive effects of natural plant materials and the potential role of these materials in chemotherapy. This current study used human EC Ishikawa cells to investigate the anti-tumor effects of PCAE in EC cells. Our results demonstrate that PCAE inhibits the growth of cancer cells and induces apoptosis, which suggests the potential applicability of PCAE as an antitumor agent.

The effect of postoperative hyperbaric oxygen treatment on intra-abdominal adhesions in rats.

Abdominal adhesions, whether caused by peritoneal trauma, radiation, infection, or a congenital condition, are associated with a wide range of complications. These complications include chronic abdominal or pelvic pain, infertility, and adhesive small bowel obstruction. Such adhesions render re-operation difficult, with attendant risks of inadvertent enterostomy and increased operation time. The purpose of this study was to investigate the potential of hyperbaric oxygen (HBO) therapy in the prevention of abdominal adhesions in an experimental animal study. A laparotomy was performed on Wistar rats to induce the formation of adhesions on the cecum and the intra-abdominal area (1 ´ 2 cm). A superficial layer of the underlying muscle from the right abdominal wall was also shaved and prepared for aseptic surgery. The rats were divided into four groups according to the duration of HBO therapy; five additional groups were designated according to the conditions of HBO therapy. When the rats were evaluated according to adhesion area and grade, a statistically significant difference was observed between the control and HBO treatment groups (p < 0.005). Results from this study suggest that HBO treatment could reduce adhesion formation; and further suggest that HBO therapy may have therapeutic potential in the treatment of postoperative peritoneal adhesion.

Demethoxycurcumin Retards Cell Growth and Induces Apoptosis in Human Brain Malignant Glioma GBM 8401 Cells.

Demethoxycurcumin (DMC; a curcumin-related demethoxy compound) has been recently shown to display antioxidant and antitumor activities. It has also produced a potent chemopreventive action against cancer. In the present study, the antiproliferation (using the MTT assay, DMC was found to have cytotoxic activities against GBM 8401 cell with IC(50) values at 22.71 µM) and induced apoptosis effects of DMC have been investigated in human brain malignant glioma GBM 8401 cells. We have studied the mitochondrial membrane potential (MMP), DNA fragmentation, caspase activation, and NF-κB transcriptional factor activity. By these approaches, our results indicated that DMC has produced an inhibition of cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects were observed to increase in proportion with the dosage of DMC treatment, and the apoptosis was induced by DMC in human brain malignant glioma GBM 8401 cells via mitochondria- and caspase-dependent pathways.

In vitro biocompatibility of thermally gelling liquid mucoadhesive loaded curcuminoids in colorectal cancer chemoprevention.

PURPOSE: Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan; it ranks top three in the cancer mortality rate. Curcuminoids are derived from the rhizome of Curcuma longa. It has shown anti-cancer activity and apoptosis induction in a variety of cancer cell lines. This aims to study the potential of Poloxamer 407 as the thermogelling and mucoadhesive polymer for development of a site-targeting delivery system to enhance the localized delivery of curcuminoids to the colorectal cells for CRC chemotherapy. METHODS: The mucoadhesive strength and rheological properties were measured as a function of poloxamer loaded with curcuminoids. RESULTS: The gelation temperature of Poloxamer 407 was found to vary with its concentration and start gelling at 37°C at the concentration of 15.5% (w/v). To ensure gelation at physiological temperature after intra-rectal application, gelation temperature was determined by rheological measurement as well as by its physical appearance. The results indicated that its mucoadhesive strength also shows a dependency on temperature, which appears to be related to the increment in the maximum strength and average strength of the polymer. CONCLUSION: The results have suggested that Poloxamer 407 could be a potential thermogelling and mucoadhesive polymer for the development of a site-targeting colorectal drug delivery system for curcuminoids in colorectal cancer therapy.

Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by Sulforaphane.

We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 µM) and subG1 (SFN 12.5 and 25 µM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential (ΔΨm). Incubations at higher SFN doses (12.5 and 25 µM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer.

Suppression of TGF-ß1/SMAD pathway and extracellular matrix production in primary keloid fibroblasts by curcuminoids: its potential therapeutic use in the chemoprevention of keloid.

Keloid is a fibrotic disease characterized by abnormal accumulation of extracellular matrix (ECM) in the dermis. It is a late spreading skin overgrowth and may be considered a plastic surgeon's nightmare. In nature, curcuminoid is composed of curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (bDMC). Curcuminoids have been found to inhibit fibrosis. However, their role in the synthesis of ECM in the keloid fibroblasts (KFs) has remained unclear. In this series of studies, a total of seven primary KFs cultures were used as the KFs model for investigating the inhibitory effect of curcuminoids on the expression of ECM and TGF-ß1. A sensitive and reproducible HPLC method was developed to provide a quantitative analysis on the cellular uptake of curcuminoids onto the KF cells. The level of ECM in the primary KFs was elevated. The elevation of ECM and TGF-ß1/p-SMAD-2 level was substantially blocked by the cellular uptake of curcumin in a dose-dependent manner in all the seven primary KFs. The results have led to the conclusion that the excessive production of ECM in the KF cells could be blocked and/or rapidly decreased by curcumin.