Article

Antiproliferative and proapoptotic effect of ascorbyl stearate in human pancreatic cancer cells: association with decreased expression of insulin-like growth factor 1 receptor

Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore 570013, India.
Digestive Diseases and Sciences (Impact Factor: 2.61). 02/2003; 48(1):230-7. DOI: 10.1023/A:1021779624971
Source: PubMed

ABSTRACT

Pancreatic cancer is an aggressive tumor with short median survival and high mortality rate. Alternative therapeutic modalities are currently being evaluated for pancreatic cancer. Here we studied the effects of ascorbyl stearate (Asc-S), a nontoxic, lipophilic derivative of ascorbic acid, on pancreatic cancer. Treatment of human pancreatic carcinoma cells with Asc-S (50-200 microM) resulted in a dose-dependent inhibition of their proliferation. Asc-S slowed down the cell cycle, accumulating, PANC-1 cells in late G2-M phase. Furthermore, Asc-S treatment (150 microM) markedly inhibited growth in soft agar and facilitated apoptosis of PANC-1 cells but not of Capan-2 cells. These effects were accompanied by a significant reduction in insulin-like growth factor 1 receptor (IGF1-R) expression, as compared to untreated controls. Interestingly, Capan-2 cells, the least responsive to Asc-S treatment, did not overexpress the IGF1-R. The results demonstrate the efficacy of Asc-S in inhibing growth of pancreatic cancer cells and warrant additional studies to explore the potential utility of this compound as an alternative and/or adjuvant therapeutic modality for pancreatic cancer.

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Available from: Akhilender Naidu, Jan 06, 2015
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    • "N-acetyl cysteine and selenium have demonstrated inhibition of tumor cell MMP-9 and invasive activities, as well as migration of endothelial cells through ECM [40] [41] [42]. Ascorbic acid demonstrates cytotoxic and antimetastatic actions on malignant cell lines [43] [44] [45] [46] [47] and cancer patients have been found to have low levels of ascorbic acid [48] [49]. Low levels of arginine, a precursor of nitric oxide (NO), can limit the production of NO, which has been shown to predominantly act as an inducer of apoptosis [50]. "
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    ABSTRACT: Chondrosarcoma (CS), a malignancy of cartilaginous origin, is an aggressive cancer with poor prognosis, due to both its aggressive metastatic spread and the lack of efficacy in current treatment modalities to prevent or counteract tumor progression. Chondrosarcomas are characterized by high levels of proteases, which are involved in the degradation of ECM and the basement membrane, thus allowing cancer cells to invade and metastasize to distal organs. Numerous clinical and experimental studies have demonstrated that high levels of uPA and MMPs are associated with tumor growth, progression, metastasis and shortened survival rates in patients. We have developed natural strategies to inhibit cancer by increasing the stability and integrity of connective tissue through the synergistic effects of selected nutrients, such as lysine, proline, ascorbic acid and green tea extract (NM). This micronutrient mixture has exhibited anticancer activity in vivo and in vitro in a large variety of cancer cell lines by simultaneously affecting several key mechanisms involved in cancer. We investigated the effect of NM in chondrosarcoma cell line SW-1353 in vitro focusing on the invasive/ metastatic parameters such as activities of uPA, MMPs and their tissue inhibitors (TIMPs), as well as the effects of various cytokines, mitogens, inducers and inhibitors on MMPs secretion. We also evaluated the effects of NM on cell invasion and migration. Cells were cultured in DEM and treated at confluence with NM at 0, 50, 100, 250, 500 and 1000 µg/ml. Analysis of uPA activity was carried out by fibrin zymography, MMPs by gelatinase zymography, TIMPs by reverse zymography, invasion through Matrigel and migration by scratch test. Chondrosarcoma expressed two bands corresponding to uPA subunits 1 and 2 at 55 and 33 kD, which were inhibited by NM in a dose-dependent manner with total block at The license for this PDF is unlimited except that no part of this digital document may be reproduced, stored in a retrieval system or transmitted commercially in any form or by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in rendering legal, medical or any other professional services.
    Full-text · Article · Jan 2015
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    • "N-acetyl cysteine and selenium have demonstrated inhibition of tumor cell MMP-9 and invasive activities, as well as migration of endothelial cells through ECM (40–42). Ascorbic acid demonstrates cytotoxic and antimetastatic actions on malignant cell lines (43–47) and cancer patients have been found to have low levels of ascorbic acid (48,49). Low levels of arginine, a precursor of nitric oxide (NO), can limit the production of NO, which has been shown to predominantly act as an inducer of apoptosis (50). "
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    Full-text · Article · Jun 2013 · International Journal of Oncology
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    • "N-acetyl cysteine and selenium have demonstrated inhibition of tumor cell MMP-9 and invasive activities, as well as migration of endothelial cells through ECM (37–39). Ascorbic acid demonstrates cytotoxic and antimeta-static actions on malignant cell lines (40–44) and cancer patients have been found to have low levels of ascorbic acid (45,46). Low levels of arginine, a precursor of nitric oxide (NO), can limit the production of NO, which has been shown to predominantly act as an inducer of apoptosis (47). "
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