Mechanistic Targets of Diallyl Trisulfide in Human Breast Cancer Cells Identified by RNA-seq Analysis

Diallyl trisulfide (DATS), a metabolic by-product of processed garlic, is highly effective in inhibiting growth of human breast cancer cells in vitro and in vivo, but the underlying mechanisms are still not fully understood. In this study, we performed RNA-seq analyses using luminal-type (MCF-7) and basal-like (MDA-MB-231) human breast cancer cells to identify mechanistic targets of DATS. The Reactome Pathway Analysis revealed upregulation of genes associated with SLIT/ROBO tumor suppressor signaling following DATS treatment in both MCF-7 and MDA-MB-231 cells. However, the expression of SLIT2 and ROBO1 proteins or their downstream target C-X-C motif chemokine receptor 4 was not affected by DATS treatment in both cell lines. The Reactome as well as the Gene Ontology Pathways Analyses of the RNA-seq data from DATS-treated cells indicated downregulation of genes associated with G2 /M phase cell cycle arrest in comparison with vehicle-treated control cells. Consistent with the RNA-seq data, DATS treatment caused a significant increase in the fraction of the G2 /M population in both cell lines when compared to corresponding control cells. In addition, Ser10 phosphorylation of histone H3, a mitotic marker, was also increased significantly following DATS treatment in MCF-7 and MDA-MB-231 cells. These results indicate that while SLIT/ROBO signaling is not affected by DATS treatment, cell cycle arrest likely contributes to the antitumor effect of this phytochemical.

Mechanistic Targets of Diallyl Trisulfide in Human Breast Cancer Cells Identified by RNA-seq Analysis

Diallyl trisulfide (DATS), a metabolic by-product of processed garlic, is highly effective in inhibiting growth of human breast cancer cells in vitro and in vivo, but the underlying mechanisms are still not fully understood. In this study, we performed RNA-seq analyses using luminal-type (MCF-7) and basal-like (MDA-MB-231) human breast cancer cells to identify mechanistic targets of DATS. The Reactome Pathway Analysis revealed upregulation of genes associated with SLIT/ROBO tumor suppressor signaling following DATS treatment in both MCF-7 and MDA-MB-231 cells. However, the expression of SLIT2 and ROBO1 proteins or their downstream target C-X-C motif chemokine receptor 4 was not affected by DATS treatment in both cell lines. The Reactome as well as the Gene Ontology Pathways Analyses of the RNA-seq data from DATS-treated cells indicated downregulation of genes associated with G2 /M phase cell cycle arrest in comparison with vehicle-treated control cells. Consistent with the RNA-seq data, DATS treatment caused a significant increase in the fraction of the G2 /M population in both cell lines when compared to corresponding control cells. In addition, Ser10 phosphorylation of histone H3, a mitotic marker, was also increased significantly following DATS treatment in MCF-7 and MDA-MB-231 cells. These results indicate that while SLIT/ROBO signaling is not affected by DATS treatment, cell cycle arrest likely contributes to the antitumor effect of this phytochemical.

Diallyl Trisulfide Inhibits Leptin-induced OncogenicSignaling in Human Breast Cancer Cells but Fails toPrevent Chemically-induced Luminal-type Cancer in Rats

Previous studies have demonstrated inhibitory effect of garlic component diallyl trisulfide (DATS) on growth of breast cancer cellsin vitro and in vivo. This study investigated the effect of DATS on oncogenic signaling regulated by leptin, which plays an importantrole in breast carcinogenesis. Leptin-induced phosphorylation and nuclear translocation of STAT3 was inhibited significantly in thepresence of DATS in MCF-7 (a luminal-type human breast cancer cell line) and MDA-MB-231 (a basal-like human breast cancer cellline). Leptin-stimulated cell proliferation, clonogenic cell survival, and migration and/or invasion ability in MCF-7 and/or MDA-MB-231cells were also suppressed by DATS treatment. DATS exposure resulted in inhibition of leptin-stimulated expression of protein and/or mRNA levels of Bcl-2, Bcl-xL, Cyclin D1, vascular endothelial growth factor, and matrix metalloproteinase-2. Western blotting revealeda decrease in protein levels of phosphorylated STAT3 in breast cancer xenografts from DATS-treated mice when comparedto controls in vivo. However, the incidence of N-methyl-N-nitrosourea-induced luminal-type breast cancer development in rats wasnot affected by oral administration of 5 mg/kg or 25 mg/kg DATS. The present study reveals that oncogenic signaling induced byleptin is inhibited in the presence of DATS but higher doses of this phytochemical may be required to achieve chemopreventive activity.

Prevention of Prostate Cancer in Transgenic Adenocarcinoma of the Mouse Prostate Mice by Yellow Passion Fruit Extract and Antiproliferative Effects of Its Bioactive Compound Piceatannol

Piceatannol (PIC), a polyphenol presents in many vegetables and fruits including yellow passion fruit extract (PFE; Passiflora edulis), has anti-cancer activity, but its molecular targets are still poorly understood. The aims of this study were to investigate the molecular mechanistic actions of PIC in prostate cancer cell lines and to test if the extract from PFE rich in PIC can affect the growth of prostate cancer cells in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. The PC-3, 22Rv1, LNCaP, and VCaP prostate cancer cells were exposed to PIC (10-40 μM), and cell viability, lactate measurement, Western blot, and flow cytometric analyses were performed. For an in vivo experiments, eight-week-old TRAMP mice (n = 10 per group each) received an aqueous extract of PFE containing 20 mg of PIC/kg or water (control group) by gavage for 4 or 10 weeks for further analyses. PIC treatment concentration- and time-dependently reduced viability of all cell lines tested. 22Rv1 and LNCaP cells treated with PIC did not exhibit any significant alteration in the intracellular accumulation of lactate. PIC treatment caused G0/G1 phase cell cycle arrest and induction of apoptosis in both LNCaP and 22Rv1 cells. PIC-treated cells exhibited altered protein levels of p53, p21, cyclin D1, and cyclin-dependent kinase 4 (cdk4). The short and long-term PFE treatments also affected p21, cyclin D1 and cdk4 and delayed disease progression in TRAMP, with a decreased incidence of preneoplastic lesions. In conclusion, PIC apparently does not alter glucose metabolism in prostate cancer cells, while cell cycle arrest and p53 modulation are likely important in anti-cancer effects of PIC alone or as a food matrix byproduct in prostate cancer cells, especially those with an androgen-dependent phenotype.

Primary Intramedullary Spinal Sarcoma : A Case Report and Review of the Current Literatures

Primary central nervous system (CNS) sarcomas are exceedingly rare, and, to the best of our knowledge, there has not yet been a report of intramedullary sarcoma. Here, we report a primary intradural intramedullary sarcoma of the spinal cord in a four-year-old boy who presented with low back pain and a radiculopathy involving both lower extremities. The tumor showed significant enhancement on magnetic resonance (MR) images due to its extreme vascularity. Gross total tumor removal was performed with microelectrical pulse recording, and the patient also received adjuvant radiotherapy and chemotherapy. After the operation, the patient's sensory deficits were improved. Because CNS dissemination is common, entire neuraxis evaluation is essential, although there was no evidence of dissemination in this case. The prognosis of primary CNS sarcoma is poor due to infiltrative nature and early CNS dissemination is common, and the treatment of choice is radical surgical resection. Adjuvant therapy is also beneficial with radiotherapy and chemotherapy.