Lutein inhibits tumor progression through the ATR/Chk1/p53 signaling pathway in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related death. In particular, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Due to tumor resistance and the toxicity of chemotherapeutic agents, it is increasingly critical to discover novel, potent antitumorigenic drugs for treating NSCLC. Lutein, a carotenoid, has been reported to exert toxic effects on cells in several tumor types. However, the detailed functions and underlying mechanisms of lutein in NSCLC remain elusive. The present study showed that lutein significantly and dose-dependently inhibited cell proliferation, arrested the cell cycle at the G0/G1 phase, and induced apoptosis in NSCLC cells. RNA-sequencing analysis revealed that the p53 signaling pathway was the most significantly upregulated in lutein-treated A549 cells. Mechanistically, lutein exerted antitumorigenic effects by inducing DNA damage and subsequently activating the ATR/Chk1/p53 signaling pathway in A549 cells. In vivo, lutein impeded tumor growth in mice and prolonged their survival. In conclusion, our findings demonstrate the antitumorigenic potential of lutein and reveal its molecular mechanism of action, suggesting that lutein is a promising candidate for clinical NSCLC treatment.

Androgen receptors expressed by prostatic stromal cells obtained from younger versus older males exhibit opposite roles in prostate cancer progression.

Aging is a major risk factor for prostate cancer (PCa), and prostatic stromal cells may also promote PCa progression. Accordingly, stromal cells do not equally promote PCa in older males and younger males. Therefore, it is also possible that the expression of androgen receptors (ARs) by prostatic stromal cells in older versus younger males plays different roles in PCa progression. Using a gene knockdown technique and coculture system, we found that the knockdown of the AR in prostatic stromal cells obtained from younger males could promote the invasiveness and metastasis of cocultured PC3/LNCaP cells in vitro. By contrast, the invasiveness and metastasis of LNCaP cells was inhibited when cocultured with prostatic stromal cells from older males that when AR expression was knocked down. Moreover, after targeting AR expression with small hairpin RNA (shRNA), matrix metalloproteinase (MMP) expression in stromal cells was observed to increase in the younger group, but decreased or remained unchanged in the older group. One exception, however, was observed with MMP9. In vivo, after knocking down AR expression in prostatic stromal cells, the incidence of metastatic lymph nodes was observed to increase in the younger age group, but decreased in the older age group. Together, these data suggest that the AR in prostatic stromal cells played opposite roles in PCa metastasis for older versus younger males. Therefore, collectively, the function of the AR in prostatic stromal cells appears to change with age, and this may account for the increased incidence of PCa in older males.

The characteristics of bone marrow-derived endothelial progenitor cells and their effect on glioma.

BACKGROUND: EPCs were isolated primarily in 1997 by Asahara et al. and recent studies indicated that bone-marrow-derived EPCs contributed little to the endothelium of tumor vessels. Tumors of the CNS system demonstrate various features of angiogenesis. METHODS: EPCs derived from rat bone marrow were isolated and cultured in M199 medium without any induced factors. EPCs were studied using immunohistochemical staining, Flow cytometry and culture under three-dimensional condition to determine EPCs' characteristics in vitro. We also established an animal model by injecting EPCs marked with Hoechst 33342 into the back of BALB/c nude mice and performed hematoxylin-eosin (HE) and immunofluorescent staining to study EPCs' features in vivo. To research effect of EPCs on glioma, animals bearing tumors model with C6 glioma were established. About 27 day after injection, we performed immunohistochemical staining and Immunofluorescence staining. RESULTS: Our results showed that EPCs derived from rat bone marrow appeared typical morphological characteristics and were positive of CD34, CD133, KDR and CD31 antigens at different time in vitro under the special M199 medium without any induced factors. The percentage of cells that expressed CD133 decreased gradually. In brief, the present study showed that EPCs derived from rat bone marrow differentiated into ECs in medium the without any induced factors and formed tubular structures in three-dimensional circumstances. Animal experiments suggested that EPCs differentiated into ECs and other else non-endothelial cells, and that EPCs contributed M199 of glioma. DISCUSSION: These findings provides some novel results about biological characteristics of EPCs in vivo and ex vivo, and an update on the effect of EPCs on glioma and which would be helpful for the overall understanding of EPCs and make EPCs to be implied on the clinical therapy.

Inhibition of fatty-acid synthase suppresses P-AKT and induces apoptosis in bladder cancer.

OBJECTIVE: To investigate the role of fatty acid synthase (FASN) in bladder transitional cell carcinoma (BTCC). METHODS: FASN expression was investigated in non-muscle-invasive BTCC tissue specimens by immunohistochemistry and BTCC cell lines by Western blot. After treatment with FASN-siRNA or FASN inhibitor cerulenin (Cer), the proliferation and apoptosis of BTCC cell lines 5637 and 253 J were determined by cell counting Kit-8 (CCK8) assay and flow cytometry respectively. The expression of p-AKT, cyclin D1 (CCND1), and apoptosis-related proteins were detected by Western blot. RESULTS: High levels of FASN expression were observed in 59% (32/54) of non-muscle-invasive BTCC tissue specimens, and FASN expression was associated with histologic grade (P < .05) and recurrence (P < .05). FASN expression was high in 6 BTCC cell lines. FASN inhibitor Cer and FASN-siRNA produced the increased apoptosis and decreased proliferation of bladder cancer cells, and caused inactivity of AKT and downregulation of CCND1. Furthermore, treatment of BTCC cell lines with Cer resulted in apoptosis via the caspase-dependent pathway involving inactivation of antiapoptotic bcl-2 protein. CONCLUSION: Our data suggest that FASN plays an important role in BTCC development. Targeting FASN may be a new therapeutic strategy for BTCC.

[Effects of K237 on the proliferation of PC-3M cells and mRNA expressions of bax and bcl-2].

OBJECTIVE: To investigate the inhibitory effect of polypeptide K237 on the proliferation of human hormone refractory prostate cancer cell line PC-3M and its possible mechanism. METHODS: PC-3M cells were divided into three experimental groups and a control, treated with polypeptide K237 at the concentration of 50, 100, 200 and 0 micromol/L, respectively, for 48 hours. The effects of K237 on the proliferation of different groups of the PC-3M cells were analyzed by MTF, and the mRNA expression levels of bax and bcl-2 were detected by RT-PCR. RESULTS: After polypeptide K237 treatment, the PC-3M cells became round, small and less transparent in cytoplasm, and some shed and suspended in the culture medium. The growth inhibition rates of the PC-3M cells were (12.6 +/- 0.95)%, (17.8 +/- 0.99)% and (27.2 +/- 1.12)% in the 50, 100 and 200 micromol/L concentration groups. RT-PCR analysis showed that the bax/beta-actin values of the 50, 100, 200 and 0 micromol/L groups were 0.919 +/- 0.071, 0.971 +/- 0.083, 0.992 +/- 0.102 and 0.889 +/- 0.067, and the bcl-2/beta-actin values of the four groups were 0.896 +/- 0.085, 0.791 +/- 0.084, 0.764 +/- 0.702 and 0.922 +/- 0.097, respectively, both with significant differences between the experimental and the control groups (P < 0.01). The mRNA expression of bax was upregulated and that of bcl-2 downregulated in a dose-dependent manner. CONCLUSION: Polypeptide K237 may induce apoptosis of PC-3M cells by affecting the expressions of bax and bcl-2, and thus suppress the proliferation of prostate cancer cells.