Casual associations between blood metabolites and colon cancer.

BACKGROUND: Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer. AIM: To investigate causal associations between blood metabolites and colon cancer. METHODS: The study utilized a two-sample Mendelian randomization (MR) analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer. The primary method of analysis used was the inverse variance weighted model. To further validate the results several sensitivity analyses were performed, including Cochran's Q test, MR-Egger intercept test, and MR robust adjusted profile score. These additional analyses were conducted to ensure the reliability and robustness of the findings. RESULTS: After rigorous selection for genetic variation, 486 blood metabolites were included in the MR analysis. We found Mannose [odds ratio (OR) = 2.09 (1.10-3.97), P = 0.024], N-acetylglycine [OR = 3.14 (1.78-5.53), P = 7.54 × 10-8], X-11593-O-methylascorbate [OR = 1.68 (1.04-2.72), P = 0.034], 1-arachidonoylglycerophosphocholine [OR = 4.23 (2.51-7.12), P = 6.35 × 10-8] and 1-arachidonoylglycerophosphoethanolamine 4 [OR = 3.99 (1.17-13.54), P = 0.027] were positively causally associated with colorectal cancer, and we also found a negative causal relationship between Tyrosine [OR = 0.08 (0.01-0.63), P = 0.014], Urate [OR = 0.25 (0.10-0.62), P = 0.003], N-acetylglycine [0.73 (0.54-0.98), P = 0.033], X-12092 [OR = 0.89 (0.81-0.99), P = 0.028], Succinylcarnitine [OR = 0.48 (0.27-0.84), P = 0.09] with colorectal cancer. A series of sensitivity analyses were performed to confirm the rigidity of the results. CONCLUSION: This study showed a causal relationship between 10 blood metabolites and colorectal cancer, of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors. The other five blood metabolites are protective factors.

Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric adenocarcinoma AGS cells.

AIM: To investigate the effect of betulinic acid (BA) on the proliferation, apoptosis and cell cycle of gastric adenocarcinoma cell AGS in vitro and the underlying mechanism. METHODS: The effect of BA on the proliferation of AGS cells was measured by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. Apoptosis was analyzed by using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-labeled flow cytometry (FCM) and Hoechst 33258 staining. The influence of BA on cell cycle of AGS cells was tested by PI staining. Both FCM and reverse transcription-PCR (RT-PCR) technologies were applied to detect the expression of Hiwi and Cyclin B1. RESULTS: BA exhibited significant cell proliferation inhibition, as well as its potency of inducing apoptosis in AGS cells in vitro in a time- and dose-dependent manner. The IC(50) value for 24 h was 18.25 microg/mL (95% confidence interval: 15.16 to 27.31 microg/mL). Cells treated with BA showed increased cell population in G(2)/M phase, with decreased S phase population. The expression of Hiwi and Cyclin B1 was down-regulated in BA-treated AGS cells in a dose-dependent manner. CONCLUSION: BA exerted potent effect on growth inhibition, G(2)/M cell cycle arrest and induction of apoptosis in AGS cells in vitro, possibly associated with the down-regulation of Hiwi and its downstream target Cyclin B1 expression. The potent antitumor capacity of BA suggested that it could be a promising new experimental anticancer agent in human gastric adenocarcinoma treatment.

[Effect of betulinic acid on inducing apoptosis of human multiple myeloma cell line RPMI-8226].

The aim of this study was to investigate the effect of betulinic acid on inducing apoptosis of human multiple myeloma RPMI-8226 cell line. The inhibitory effect of betulinic acid on proliferation and its inducing apoptosis effect, influence on cell cycle and induced morphological changes of RPMI-8226 were evaluated by MTT, flow cytometry Annexin-V/PI double staining, flow cytometry with PI staining and fluorescence microscopy with Hoechst33258 staining, respectively. The transcription level changes of bcl-xl gene and caspase 3 which are two kinds of apoptosis related protein gene were determined by RT-PCR. The results showed that within a certain range of concentration (0, 5, 10, 15, 20 microg/ml), IC50 of betulinic acid to RPMI-8226 at 24 hours was 10.156+/-0.659 microg/ml, while the IC50 at 48 hours was 5.434+/-0.212 microg/ml, and its inhibiting effect on proliferation of RPMI-8226 showed both time-and dose-dependent manners. Flow cytometry with Annexin-V/PI double staining revealed that apoptotic rate of RPMI-8226 cells increased as betulinic acid concentration increased. Flow cytometry with PI staining showed that the ratio of cells in G0/G1 phase increased, while it in S phase decreased, and ratio of cells at G2/M phase did not present a significant change. Morphological differences were typical and obvious between cells in treated and control groups under fluorescence microscope using Hoechst33258 staining. RT-PCR detection of caspase 3 gene indicated that its transcription level showed an increasing trend as the concentration of betulinic acid increased, while the bcl-xl showed the opposite trend. It is concluded that the betulinic acid can induce apoptosis of RPMI-8226 within a certain range of concentration in a time- and dose-dependent manners. This phenomenon may be related to the transcriptional level increase of caspase 3 gene and decrease of bcl-xl. Betulinic acid also affects G1/S in cell cycle which arrests cells at phase G0/G1.