Impact of Taurine on the proliferation and apoptosis of human cervical carcinoma cells and its mechanism.

BACKGROUND: Cervical cancer has the fourth highest incidence and mortality rate of all cancers in women worldwide; it seriously harms their physical and mental health. The aim of this study was to observe the roles and preliminary mechanism of Taurine (Tau)-induced apoptosis in cervical cancer cells. METHODS: Cells from the human cervical cancer cell line SiHa were transfected with the recombinant plasmid pEGFP-N1-MST1 (mammalian sterile 20-like kinase 1); then, the cell proliferation activity was analyzed by the MTT assay, cell apoptosis by flow cytometry, and the related protein levels by Western blotting. RESULTS: Tau inhibited the proliferation of SiHa cells and induced apoptosis in these cells (the apoptotic rate was 21.95% in the Tau 160 mmol/L group and 30% in the Tau 320 mmol/L group), upregulated the expression of the MST1 (control, 0.53; Tau 40-320 mmol/L groups, 0.84-1.45) and Bax (control, 0.45; Tau 40-320 mmol/L groups, 0.64-1.51) proteins (P < 0.01), and downregulated the expression of Bcl-2 (control, 1.28, Tau 40-320 mmol/L groups, 0.93-0.47) (P < 0.01). The overexpression of MST1 promoted the apoptosis of SiHa cells, enhanced the apoptosis-inductive effects of Tau (P < 0.01), upregulated the expression of the proapoptotic proteins p73, p53, PUMA (p53 upregulated modulator of apoptosis), and caspase-3, and promoted the phosphorylation of YAP (Yes-associated protein). CONCLUSIONS: Tau inhibited the proliferation and induced the apoptosis of cervical cancer SiHa cells. The MST1 protein plays an important role in the Tau-induced apoptosis of cervical cancer cells.

High expression of IGFBP7 in fibroblasts induced by colorectal cancer cells is co-regulated by TGF-ß and Wnt signaling in a Smad2/3-Dvl2/3-dependent manner.

Fibroblasts in the tumor microenvironment are a key determinant in cancer progression and may be a promising target for cancer therapy. Insulin-like growth factor binding protein 7 (IGFBP7) is known as a tumor suppressor in colorectal cancer (CRC). The present study investigated the inductive mechanism of IGFBP7 expression in fibroblasts by supernatant from the CRC cell line, SW620. The results showed that the expression of IGFBP7 was up-regulated in the fibroblasts when treated with SW620 supernatant and exogenous TGF-ß1. The IGFBP7 induced by SW620 supernatant or TGF-ß1 was partially inhibited by the TGF-ß1 specific antibody AF and TGF-ß1 receptor antagonist SB431542. The Wnt signaling-targeted genes, c-Myc, CCND1 and the proteins Dvl2/3, were all up-regulated in fibroblasts expressing high levels of IGFBP7, and the up-regulation could be inhibited both by the Wnt signaling antagonist Dickkopf-1 (DKK1) and by the TGF-ß1 receptor antagonist SB431542. In conclusion, CRC cells promote the high expression of IGFBP7 in fibroblasts, most likely through the co-regulation of TGF-ß and Wnt signaling in a Smad2/3-Dvl2/3 dependent manner. Taken together, these data suggest that the fibroblasts could be a novel therapeutic target in tumor therapy.

Nkx2-1: a novel tumor biomarker of lung cancer.

Nkx2-1 (Nkx homeobox-1 gene), also known as TTF-1 (thyroid transcription factor-1), is a tissue-specific transcription factor of the thyroid, lung, and ventral forebrain. While it has been shown to play a critical role in lung development and lung cancer differentiation and morphogenesis, molecular mechanisms mediating Nkx2-1 cell- and tissue-specific expression in normal and cancerous lungs have yet to be fully elucidated. The recent identification of prognostic biomarkers in lung cancer, particularly in lung adenocarcinoma (ADC), and the different reactivity of patients to chemotherapeutic drugs have opened new avenues for evaluating patient survival and the development of novel effective therapeutic strategies. The function of Nkx2-1 as a proto-oncogene was recently characterized and the gene is implicated as a contributory factor in lung cancer development. In this review, we summarize the role of this transcription factor in the development, diagnosis, and prognosis of lung cancer in the hope of providing insights into the utility of Nkx2-1 as a novel biomarker of lung cancer.

Anticancer effects of Chinese herbal medicine, science or myth?

Currently there is considerable interest among oncologists to find anticancer drugs in Chinese herbal medicine (CHM). In the past, clinical data showed that some herbs possessed anticancer properties, but western scientists have doubted the scientific validity of CHM due to the lack of scientific evidence from their perspective. Recently there have been encouraging results, from a western perspective, in the cancer research field regarding the anticancer effects of CHM. Experiments showed that CHM played its anticancer role by inducing apoptosis and differentiation, enhancing the immune system, inhibiting angiogenesis, reversing multidrug resistance (MDR), etc. Clinical trials demonstrated that CHM could improve survival, increase tumor response, improve quality of life, or reduce chemotherapy toxicity, although much remained to be determined regarding the objective effects of CHM in human in the context of clinical trials. Interestingly, both laboratory experiments and clinical trials have demonstrated that when combined with chemotherapy, CHM could raise the efficacy level and lower toxic reactions. These facts raised the feasibility of the combination of herbal medicines and chemotherapy, although much remained to be investigated in this area.

IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis with its expression associated with DNA hypomethylation of exon 1.

Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.

[VNTR polymorphism of C6orf37 in Chinese population].

OBJECTIVE: To identify a novel VNTR in C6orf37 and to detect the C6orf37 VNTR polymorphism distribution in Chinese population. METHODS: RT-PCR and sequencing were conducted to identify VNTR alleles in the variable region of C6orf37.SSLP and DHPLC were applied in detecting the VNTR genotypes in 166 Chinese individuals. RESULT: A novel VNTR sequence was found in the second exon of C6orf37, which was composed of 15 base pairs encoding 5-amino-acid (G-G-D-F-G). The repeat times ranged from 3 to 5. There were three common alleles containing three repeats (a), four repeats (b) and five repeats (c), respectively, which produced three homozygotes (a/a, b/b and c/c) and three heterozygotes (a/b, a/c and b/c). The frequency of a, b, c alleles were 0.145, 0.304, 0.551, respectively in Chinese population. Heterozygosity (H) was 0.583. Polymorphism information content (PIC) was 0.510. The screened result of DHPLC was consistent with that of SSLP. CONCLUSION: A novel highly polymorphic VNTR in C6orf37 exists in Chinese population. DHPLC is the most efficient technique for screening VNTR polymorphism.

Identification of a novel VNTR polymorphism in C6orf37 and its association with colorectal cancer risk in Chinese population.

BACKGROUND: C6orf37 was a gene up-regulated in colorectal adenoma in our previous study. A variable region of C6orf37 sequence was found when we blasted its full sequence with NCBI nucleotide database. METHODS: RT-PCR and sequencing were conducted to identify the variable region of C6orf37 as VNTR. DHPLC was applied to detect the VNTR genotypes in 122 colorectal carcinoma patients and 166 healthy controls. RESULTS: A novel VNTR sequence found in C6orf37 second exon was composed of 15 base pair consensus sequence encoding 5-amino-acid (G-G-D-F-G). The repeat timePOST alleles contain three repeats (a), 4 repeats (b) and 5 repeats (c), respectively, which produced 3 homozygotes (a/a, b/b and c/c) and 3 heterozygotes (a/b, a/c and b/c). a, b, c allele frequencies were 0.145, 0.304, 0.551, respectively in Chinese population. Heterozygosity (H) was 0.583. Polymorphism information content (PIC) was 0.510. The distribution of genotypes and allele frequencies of the VNTR reached no significant difference between patients and healthy controls and there was no correlation between VNTR polymorphism and colorectal cancer clincopathological features. CONCLUSION: A novel VNTR polymorphism in C6orf37 exists in Chinese population and is not associated with colorectal cancer risk.

Autocrine stimulation in colorectal carcinoma (CRC): positive autocrine loops in human colorectal carcinoma and applicable significance of blocking the loops.

Many tumors co-express growth factors and their receptors; thus, the concept of autocrine secretion was proposed to explain the unrestrained growth of the malignant cells. Autocrine stimulation refers to positive autocrine secretion, which functions to stimulate cell growth. Many of the positive autocrine loops have been demonstrated in human colorectal carcinoma (CRC), which are considered to play an important role in the initiation and progression of the cancer. These autocrine loops provide information for prognostic markers and targets for biological therapies of CRC. Interruption of the autocrine loops could potentially inhibit malignant cell growth. The field is encouraging but further research is needed.