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Background Tumor cell metabolic reprogramming is crucial for the malignant behavior of cancer cells by promoting their proliferation. However, little is known on how transient receptor potential 7 (TRPM7) modulates metabolic reprogramming in ovarian cancer. Methods The effects of TRPM7 silencing on transcriptome profile, glucose uptake, lactic acid production, extracellular acidification rate (ECAR), oxygen consumption rate (OCR), intracellular ROS and ATP levels, and NAD+/NADH ratios in ovarian cancer cells were examined. The impacts of TRPM7 silencing on the levels of glycolysis-related HK2, PDK1 and oxidative phosphorylation (OXPHOS)-related IDH3B and UQCRC1, HIF-1α expression and AMPK phosphorylation were determined in ovarian cancer. The effect of AMPK activity on HIF-1α ubiquitination degradation was investigated in ovarian cancer cells. Results Compared with the control, TRPM7 silencing suppressed the proliferation of ovarian cancer cells by shifting preferable glycolysis to OXPHOS. In parallel, TRPM7 silencing decreased the glucose uptake of tumor-bearing mice and TRPM7 levels were negatively correlated with IDH3B and UQCRC1, but positively with HK2 and PDK1 expression in ovarian cancer tissues. Mechanistically, TRPM7 silencing significantly increased AMPK phosphorylation and decreased HIF-1α protein levels in ovarian cancer, particularly in HIF-1α silencing cells. The shifting from glycolysis to OXPHOS by TRPM7 silencing was abrogated by HIF-1α over-expression and impaired by inhibiting AMPK activity in ovarian cancer cells. Moreover, enhanced AMPK activation inhibited glycolysis, which was abrogated by HIF-1α over-expression in ovarian cancer cells. Moreover, the enhanced AMPK activation promoted HIF-1α ubiquitination degradation. Conclusions TRPM7 silencing enhanced AMPK activation to shift glycolysis to oxidative phosphorylation by promoting HIF-1α ubiquitination degradation in ovarian cancer. Hence, TRPM7 may be a therapeutic target for intervention of ovarian cancer.

Our previous study demonstrated that the melastatin-related transient receptor potential channel 7 (TRPM7) was highly expressed in ovarian carcinomas and its overexpression was significantly associated with poor prognosis in ovarian cancer patients. However, the function of TRPM7 in ovarian cancer is mostly unknown. In this study, we examined the roles of TRPM7 in ovarian cancer cell proliferation, migration and invasion. We found that short hairpin RNA interference-mediated silence of TRPM7 significantly inhibited cell proliferation, colony formation, migration and invasion in multiple ovarian cancer cell lines. Mechanistic investigation revealed that silence of TRPM7 decreased phosphorylation levels of Akt, Src and p38 and increased filamentous actin and focal adhesion number in ovarian cancer cells. Thus, our results suggest that TRPM7 is required for proliferation, migration and invasion of ovarian cancer cells through regulating multiple signaling transduction pathways and the formation of focal adhesions.

The aim of this study was to explore the molecular mechanisms of the diallyl disulfide (DADS)-mediated downregulation of LIM kinase-1 (LIMK1) and the consequent inhibition of the migration and invasion of human colorectal cancer cells. RNA interference technology was used to establish stable LIMK1-miRNA/SW480 cell lines. The effects of DADS and LIMK1 RNA interference on the migration and invasion of SW480 cells were observed by scratch wound healing assay and Transwell migration assay. The effects of DADS on signaling molecules of the Rac1-Rho kinase (ROCK)1/p21-activated kinase (PAK)1-LIM kinase (LIMK)1-actin depolymerizing factor (ADF)/cofilin pathway in SW480 cells were examined by RT-PCR and western blot analysis. The healing and migration rate of the SW480 cells was significantly reduced and the cell penetrating ability was significantly suppressed (P

To investigate the expression of miR-23a and metastasis suppressor 1 (MTSS1) and their clinical significance in colon carcinoma.A total of 92 cases of colon carcinomas were collected with both the tumor and paired normal tissue samples for the study. The miR-23a targeting MTSS1 was evaluated by luciferase reporter vector. Cell invasion potential was evaluated by trans-well invasion assay. In-situ hybridization and immunohistochemistry were used to detect miR-23a and MTSS1 expression.MiR-23a downregulated the expression of MTSS protein and enhanced the invasiveness of colon carcinoma. The expression rates of miR-23a and MTSS1 were 87.0% (80/92) and 17.4% (16/92) in colon carcinoma cases, respectively (P0.01). The up-regulation of miR-23a expression was associated with an advanced clinical stage (P = 0.029) and depth of invasion (P = 0.000). The expression of miR-23a was higher in the tumors with lymph node metastasis than those without (P = 0.041). Down-regulation of MTSS1 expression was associated with an advanced clinical stage (P = 0.027) and depth of invasion (P = 0.017). The expression of MTSS1 was lower in the tumors with lymph node metastasis than those without (P = 0.009). The expression of miR-23a had significantly negative correlation with that of MTSS1 (r = -0.594, P = 0.013).MiR-23a expression promotes colon carcinoma cell growth, invasion and metastasis through inhibition of MTSS gene. Both the low expression of MTSS1 and high expression of miR-23a may serve as important biological markers for the malignant phenotypes of colon cancer, such as invasion and metastasis.

Diabetic nephropathy (DN) is a long-term complication of diabetic mellitus. Numerous reports have suggested that oxidative stress is defined as the excessive production of reactive oxygen species (ROS) surpassing existing anti-oxidative defense mechanisms, and plays a critical role in the pathogenesis of diabetic nephropathy. Rosa laevigata Michx. (RLM) is the commonly used traditional Chinese medicine for the treatment of chronic urinary tract infections and anti-oxidative treatments, and has been shown to have a renal protective effect in diabetic rats. In the present study, we further investigate the effects of RLM on oxidative stress in the kidneys of streptozotocin-induced diabetic rats with DN. Our results suggest that RLM significantly ameliorates renal dysfunction in diabetic rats. The protection against the development of DN by RLM treatment involves increasing the activity of superoxide dismutase and total anti-oxidant capacity, decreasing the levels of malondialdehyde and ROS, and inhibiting the expression of nuclear factor-κB p65 and monocyte chemoattractant protein-1 at both the protein and mRNA levels with a concomitant increase in the expression of the IκBα protein. These results highlight the potential therapeutic application of RLM for the treatment of DN.

Our previous study revealed that diallyl disulfide (DADS) significantly inhibited cell proliferation and induced cell cycle arrest at G(2)/M phase of human colon cancer SW480 cells. However, the molecular mechanism of cell cycle arrest remains unclear. This study was to investigate the role and the molecular mechanism of DADS in the induction of cell cycle arrest of human colon cancer cell line SW480.Proliferation of SW480 cells after DADS treatment was measured by MTT assay and cell counting. Phase distribution of cell cycle was analyzed by flow cytometry. Expressions of PCNA, p53, p21(WAF1) and cyclin B1 were detected by immunohistochemistry and western blot.DADS (30-70 microg/mL) significantly inhibited proliferation and retarded the population doubling time of colonies in SW480 cells. Compared with the control group, SW480 cells were markedly accumulated at G(2)/M phase after the treatment with DADS (p0.05). Moreover, DADS remarkably decreased the protein contents of PCNA, p53 and cyclin B1, but increased the expression of p21(WAF1) in a time- and dose-dependent manner.DADS induces G(2)/M arrest in human colon cancer SW480 cells, probably through the downregulation of PCNA, p53 and cyclin B1 and upregulation of p21(WAF1).

To examine the differentiation induction and growth inhibition of HL-60 cells by diallyl disulfide (DADS), and its relationship with the alterations of histone acetylation and p21(WAF1) expression in vitro and in vivo.Differentiation was studied by nitroblue tetrazolium (NBT) reduction of HL-60 cell in vitro. HL-60 cells 5x10(6) were injected into the right side of the peritoneal cavity of severe combined immunodeficiency (SCID) mice. When the peritoneal neoplasms were detected, the SCID mice were randomly divided into 3 groups and received an ip injection of vehicle alone (NS), DADS or sodium butyrate (SB). The growth inhibition of peritoneal neoplasms induced by DADS was observed by a growth curve. The cycle distribution of HL-60 cells in SCID mice was monitored by flow cytometry. The expression of acetylated histone H3, H4 and p21(WAF1) were measured by Western blot.After treatment with DADS for 0-72 h, the NBT reduction ability of HL-60 cells increased in a time-dependent manner, compared with no treatment of HL-60 cells. In the HL-60 cells treated with DADS for 24 h, the expression of acetylated histone H3, H4, and p21(WAF1) increased obviously. After treatment with DADS, tumor growth was markedly suppressed. HL-60 cells from mice treated with DADS were blocked in the G1 phase, from 25.4% to 63.4%. The tumors from the mice treated with DADS showed an increase of acetylated histone H3, H4, and p21(WAF1).DADS could induce differentiation and inhibit the growth of HL-60 cells through increasing the expression of acetylated histone H3, H4, and p21(WAF1) in vitro and in vivo.

Diallyl disulfide (DADS) can inhibit growth of various cancer cell lines in vitro, but little is known about its in vivo antitumor effect. This study was designed to investigate effect of DADS on growth of human gastric carcinoma MGC803 cells xenograft in BALB/C nude mice.MGC803 cells, with or without 1-day treatment of DADS (30 mg/L), were subcutaneously transplanted into the right axial regions of nude mice. The xenograft tumor growth in mice was observed after in vitro treatment or intraperitoneal injection of DADS. Proliferating cell nuclear antigen (PCNA) expression was detected by Western blot.No xenograft tumor was observed in the nude mice inoculated with DADS-treated MGC803 cells. When injected with 50, 100, and 200 mg/kg of DADS, the inhibition rate of tumor growth in the nude mice inoculated with untreated MGC803 cells were 27.8%, 66.1%, and 73.0%; the expression of PCNA was inhibited.DADS could suppress incidence of human gastric carcinoma xenograft in BALB/C nude mice, and inhibit growth of transplanted tumor.