An Investigation into the Cytotoxic Effects of 13-Acetoxysarcocrassolide from the Soft Coral Sarcophyton crassocaule on Bladder Cancer Cells

Active compounds from natural products have been widely studied. The anti-tumor effects of 13-acetoxysarcocrassolide isolated from Formosan soft coral Sarcophyton crassocaule on bladder cancer cells were examined in this study. An MTT assay showed that 13-acetoxysarcocrassolide was cytotoxic to bladder female transitional cancer (BFTC) cells. We determined that the BFTC cells underwent cell death through apoptosis by flow cytometry. Due to the highly-migratory nature of the BFTC cells, the ability of 13-acetoxysarcocrassolide to stop their migration was assessed by a wound healing assay. To determine which proteins were affected in the BFTC cells upon treatment, a comparative proteomic analysis was performed. By LC-MS/MS analysis, we identified that 19 proteins were up-regulated and eight were down-regulated. Seven of the proteins were confirmed by western blotting analysis. This study reveals clues to the potential mechanism of the cytotoxic effects of 13-acetoxysarcocrassolide on BFTC cells. Moreover, it suggests that PPT1 and hnRNP F could be new biomarkers for bladder cancer. The results of this study are also helpful for the diagnosis, progression monitoring and therapeutic strategies of transitional cell tumors

Matrix metalloproteinase-1 polymorphism (-1607G) and disease severity in non-cystic fibrosis bronchiectasis in Taiwan.

OBJECTIVES: Bronchiectasis is characterized by an irreversible dilatation of bronchi and is associated with lung fibrosis. MMP-1 polymorphism may alter its transcriptional activity, and differentially modulate bronchial destruction and lung fibrosis. DESIGN: To investigate the association of MMP-1 polymorphisms with disease severity in non-cystic fibrosis (CF) bronchiectasis patients, 51 normal subjects and 113 patients with bronchiectasis were studied. The associations between MMP-1 polymorphisms, lung function, and disease severity evaluated by high resolution computed tomography (HRCT) were analyzed. RESULTS: The frequency of MMP-1(-1607G) allele was significantly higher in patients with bronchiectasis than normal subjects (70.8% vs 45.1%, p<0.01). Forced expiratory volume in 1 second (FEV1) was decreased in bronchiectasis patients with 1G/1G (1.2±0.1 L, n = 14) and 1G/2G (1.3±0.1 L, n = 66) genotypes compared to the 2G/2G genotype (1.7±0.1 L, n = 33, p<0.01). Six minute walking distance was decreased in bronchiectasis patients with 1G/1G and 1G/2G compared to that of 2G/2G genotype. Disease severity evaluated by HRCT score significantly increased in bronchiectasis patients with 1G/1G and 1G/2G genotypes compared to that of 2G/2G genotype. Bronchiectasis patients with at least one MMP-1 (-1607G) allele showed increased tendency for hospitalization. Serum levels of pro-MMP-1, active MMP-1 and TGF-β1 were significantly increased in patients with bronchiectasis with 1G/1G and 1G/2G genotype compared with 2G/2G genotype or normal subjects. Under IL-1β stimulation, peripheral blood monocytes from subjects with 1G/2G or 1G/1G genotype secreted higher levels of TGF-β1compared to subjects with 2G/2G genotype. CONCLUSION: This is the first report to address the influence of MMP-1 polymorphisms on lung function and airway destruction in non-CF bronchiectasis patients. Bronchiectasis patients with MMP-1(-1607G) polymorphism may be more vulnerable to permanent lung fibrosis or airway destruction due to the enhanced MMP-1 and TGF-β1 activity. Upregulated MMP-1 activity results in proteolytic destruction of matrix, and leads to subsequent fibrosis

Association of <i>MMP-1</i> (-1067GG) polymorphisms and number of involved lobe in bronchiectasis.

<p>Association of <i>MMP-1</i> (-1067GG) polymorphisms and number of involved lobe in bronchiectasis.</p

The serum level of TGF-β1 in normal subjects and patients with bronchiectasis.

<p>The serum level of TGF-β1 in patients with bronchiectasis having at least one -1607G of <i>MMP-1</i> was measured and compared to different clinical setting. Individual difference was marked as p-values among different settings.</p

HRCT grading system for patients with bronchiectasis.

<p>Each lobe of both lungs is graded for bronchiectatic changes on a scale of 0 to 3 (lingula was scored as a separate lobe), giving a maximum of 18 points. (A) Represents score 0: no bronchiectasis. (B) Represents score 1 in one lobe: one bronchopulmonary segment involved (C) Represents score 2 in one lobe: more than one bronchopulmonary segment involved. Total Score was 8 in this figure due to four lobes involved. (D) Represents score 3 in one lobe: grossly cystic bronchiectasis. Total Score was 12 in this figure due to three lobes involved.</p

Association of <i>MMP-1</i> (-1607G) polymorphisms with lung function, walking distance, CT score and hospitalization.

<p>Abbreviations: FVC: forced vital capacity; L: liter; % pred.: percentage of predicted value; FEV1: forced expiratory volume in the first second; CT: computed tomography.</p