ascorbic-acid and Testicular-Neoplasms

Metastasis-associated protein 1 (MTA1) is involved in tumor growth and metastasis of cancers. Being a component of nucleosome remodeling and histone deacetylase complex, the protein is also associated with DNA damage response pathway. Since the protein is involved in cancer pathology, we first investigated the effects of bleomycin, etoposide, and cisplatin (BEP) on MTA1 signaling in the testis. Second, since the antioxidants (AOs) have protective effects, we further investigated whether or not an AO cocktail modulates the effects of the drugs. Adult male Sprague Dawley rats (N = 4) were treated either with saline, or AO (α-tocopherol, l-ascorbic acid, zinc, and selenium), or therapeutic dose levels of etoposide (15 mg/kg) and cisplatin (3 mg/kg) from day 1-4 of the week and B (1.5 mg/kg) on the second day of the week, or BEP + AO. The real-time polymerase chain reaction showed that MTA1 and MTA1s (short form) gene expression was downregulated in AO (100% and 100%), BEP (86% and 71%), and BEP + AO (97% and 93%) groups. Western blotting and immunohistochemistry results showed that unnormalized MTA1 protein expression was upregulated in AO (38%) and BEP + AO (34%) groups; however, the MTA1/β-actin ratio was upregulated in all treated groups (21, 19, and 15%, respectively). In conclusion, the results indicate that both BEP and AO suppress MTA1 and MTA1s transcription, which may render the germ cells to be more prone to apoptosis. However, upregulation of MTA1 protein expression may be related to induced DNA damage. Modulation of MTA1 signaling is a novel mechanism of action of BEP and AO, which may be useful in developing newer anticancer drugs.

Topics: Actins; alpha-Tocopherol; Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Bleomycin; Cisplatin; Disease Models, Animal; DNA Damage; Dose-Response Relationship, Drug; Etoposide; Histone Deacetylases; Male; Proteins; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Selenium; Signal Transduction; Testicular Neoplasms; Testis; Up-Regulation

Desorption electrospray ionization mass spectrometry (DESI-MS) has been successfully used to discriminate between normal and cancerous human tissue from different anatomical sites. On the basis of this, DESI-MS imaging was used to characterize human seminoma and adjacent normal tissue. Seminoma and adjacent normal paired human tissue sections (40 tissues) from 15 patients undergoing radical orchiectomy were flash frozen in liquid nitrogen and sectioned to 15 μm thickness and thaw mounted to glass slides. The entire sample was two-dimensionally analyzed by the charged solvent spray to form a molecular image of the biological tissue. DESI-MS images were compared with formalin-fixed, hematoxylin and eosin (H&E) stained slides of the same material. Increased signal intensity was detected for two seminolipids [seminolipid (16:0/16:0) and seminolipid (30:0)] in the normal tubule testis tissue; these compounds were undetectable in seminoma tissue, as well as from the surrounding fat, muscle, and blood vessels. A glycerophosphoinositol [PI(18:0/20:4)] was also found at increased intensity in the normal testes tubule tissue when compared with seminoma tissue. Ascorbic acid (i.e., vitamin C) was found at increased amounts in seminoma tissue when compared with normal tissue. DESI-MS analysis was successfully used to visualize the location of several types of molecules across human seminoma and normal tissues. Discrimination between seminoma and adjacent normal testes tubules was achieved on the basis of the spatial distributions and varying intensities of particular lipid species as well as ascorbic acid. The increased presence of ascorbic acid within seminoma compared with normal seminiferous tubules was previously unknown.

Topics: Ascorbic Acid; Biomarkers, Tumor; Case-Control Studies; Glycerophospholipids; Humans; Male; Molecular Imaging; Seminoma; Spectrometry, Mass, Electrospray Ionization; Testicular Neoplasms

Current treatment of testicular cancer is associated with secondary malignancy, infertility, and cytotoxicity. Based on reported antimetastatic potential, we investigated the effect of a nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract on human testis cancer cell line NT 2/DT by measuring cell proliferation/cytotoxicity, modulation of MMP-2 and MMP-9 secretion, and cancer cell invasive potential. Human testis cancer cells NT 2/DT (ATCC) were grown in DME medium. At near confluence, the cells were treated with NM dissolved in media and tested at 0,10, 50, and 100 microg/mL in triplicate at each dose. Cells were also treated with PMA 200 ng/mL to study enhanced secretion of MMP-9. Cell proliferation/cytotoxicity was evaluated by MTT assay, MMP activity by gelatinase zymography, and invasion through Matrigel. The nutrient mixture showed no significant effect on testis cancer cell growth. Zymography demonstrated secretion of MMP-2 by untreated human testis cancer cells and MMP-9 with PMA induction. NM inhibited secretion of both MMPs in a dose-dependent fashion with virtual total inhibition of MMP-9 at 100 microg/mL. Invasion of human testis cancer cells through Matrigel was reduced by 84% at 50 microg/mL and at 100 microg/mL (p = 0.004). NM significantly inhibited MMP secretion and matrix invasion in testicular cancer cells without toxic effect, indicating potential as an anticancer agent.

Topics: Amino Acids; Antineoplastic Agents; Antioxidants; Arginine; Ascorbic Acid; Camellia sinensis; Cell Line, Tumor; Cell Proliferation; Collagen; Drug Combinations; Humans; Laminin; Lysine; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Neoplasm Invasiveness; Plant Extracts; Proline; Proteoglycans; Testicular Neoplasms

The nutritional status of 14 patients with metastatic testicular teratomas was measured longitudinally through four courses of treatment with vinblastine and bleomycin, or vinblastine, bleomycin and cis platinum regimens. On each regimen patients lost weight during each course and did not entirely regain it between courses. The nutritional status with respect to retinol and vitamins E, B1 and B6 also fell during each course. The fall in plasma retinol levels was correlated with a fall in the plasma level of retinol-binding protein (RBP). In patients treated with the vinblastine and bleomycin regimen, plasma retinol levels were higher at the beginning of the fourth course than at the start of the treatment, possibly due to improved synthesis of RBP. In contrast, there was no overall improvement in B1 status.

Topics: Adult; Ascorbic Acid; Avitaminosis; Bleomycin; Cisplatin; Drug Therapy, Combination; Humans; Longitudinal Studies; Male; Middle Aged; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Teratoma; Testicular Neoplasms; Vinblastine; Vitamin A; Vitamin E; Vitamins