Cathepsins D, B and L in Breast Carcinoma and in Transformed Human Breast Epithelial Cells (HBEC)

Lah, Tamara T.; Calaf, Gloria M.; Kálmán, Endre; Shinde, B. G.; Russo, José; Jarosz, David; Zabrecky, James R.; Somers, Robert G.; Daskal, Ierachmiel

doi:10.1515/bchm3.1995.376.6.357

Cited by 33 publications

(14 citation statements)

References 15 publications

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“…Enzyme activity in the media could be activated by pepsin, resulting in a several fold increase in Cat B activity ( Table 1). The highest activation was observed in the medium of the D3-1Tras cell line, in agreement with our immunochemical data showing that Cat B was secreted mostly as a 46 kDa precursor [25,26]. Immunocytochemical analysis showed heterogeneity in intracellular Cat B staining: only 5-20% of cells in the control and carcinogen-treated lines seemed to express Cat B (Fig.…”

Section: Biochemical Changes Induced In the Carcinogen And C-ha-ras Osupporting

confidence: 90%

“…In general, secretion of the precursor form(s) results mostly from an inefficient interaction between the lysosomal enzyme precursors and the mannose-6-phosphate or other receptors in the trans Golgi network [28]. This may have occurred in both c-Ha-ras transformed cell lines, where markedly lowered intracellular concentrations of the precursors were found [26]. The synthesis and the secretion of a lysosomal enzyme are under different control mechanisms and may not be linked.…”

Section: Discussionmentioning

confidence: 99%

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Cathepsins D, B, and L in transformed human breast epithelial cells

Lah

Calaf

Kálmán

et al. 1996

Breast Cancer Res Tr

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To investigate the regulation of lysosomal enzymes during carcinogenesis, we measured cathepsins (Cats) D, B, and L in MCF-10F, which is a human breast epithelial cell line, and cells evolved after treatment with carcinogen and transfected with c-Ha-ras oncogene. The clones used in this study, MCF-10FTras, D3, D3-1, and D3-1Tras, expressed no estrogen receptors and gradually increased invasive potential, while oncogene-transfected lines were also tumorigenic in SCID mice [16, 19]. Cats D, B, and L were determined in the cells and in cell media using enzyme-linked immunosorbent assay (ELISA), specific enzyme activity measurements, and immunocytochemistry. The major intra- and extracellular lysosomal proteinase in these cells was Cat D (30-180 pm/mg), followed by Cat B (2-10 pm/mg) and Cat L (1-5 pm/mg). An inverse relationship between intracellular Cat D levels and invasive potential of carcinogen-treated and c-Ha-ras oncogene-transfected cell lines was observed. No significant changes in extracellular concentration of Cat D precursor in this series of cell lines was observed. Intracellular levels of Cats B and L were unchanged or slightly lower in carcinogen-treated D3 and D3-1 cells, as well as in MCF-10FTras. On the other hand, in D3-1Tras cell line, evolving from c-Ha-ras transfected D3-1 line, 3.5 fold and 4.4 fold increases in Cat B and Cat L, respectively, but a 2 fold decrease in Cat D, were observed compared to the parental cell line. Immunocytochemical staining showed a granular, polarized perinuclear and cytoplasmic staining of cathepsins in all cell lines. Cysteine proteinases stained more frequently and more intensely in D3-1Tras compared to other lines, confirming the immunochemical assays. We hypothesize that several molecular events, caused by a carcinogen and an oncogene such as c-Ha-ras, are needed to increase Cat B and Cat L, but not Cat D, expression. Therefore, the cysteine and aspartic lysosomal proteinases are differentially expressed in the breast cell lines with more invasive phenotype.

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Section: Biochemical Changes Induced In the Carcinogen And C-ha-ras Osupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Cathepsins D, B, and L in transformed human breast epithelial cells

Lah

Calaf

Kálmán

et al. 1996

Breast Cancer Res Tr

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“…49) An increased expression of cathepsin-D in malignant breast tissue when compared to normal breast tissue observed in our investigation is in line with previous reports. 50) Reversion of their levels in drug treated animals may be due to the stabilizing property of the drug on lysosomal membrane which could have been imparted by the flavonoids, as it is well established that flavonoids have inhibiting property on lysosomal membranes. The drug may modify the lysosomal membrane in such a way that it is capable of fusing with the plasma membrane and thereby preventing the discharge of acid hydrolases or by inhibiting the release of lysosomal enzymes.…”

Section: Discussionmentioning

confidence: 99%

Anticancer Effect of Kalpaamruthaa on Mammary Carcinoma in Rats with Reference to Glycoprotein Components, Lysosomal and Marker Enzymes

Veena

Shanthi

Sachdanandam

2006

Biological & Pharmaceutical Bulletin

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Cancer accounts for high morbidity and high mortality rate throughout the world. Cancer of breast is common in women in developed countries and more than 40% of all breast cancer cases are found in developing countries.1) Cancer is based on genetic and epigenetic alterations that affect the regulation and function of genes. These pathologic changes are selected during progression to yield cells that multiply aggressively beyond the limits normally set by their intrinsic proliferative capacity, neighboring cells, limited mitogens, and blood supply. It is expected that the cataloging of specific changes in gene expression will provide diagnostic markers for any given type. Furthermore, proteins encoded by specific genes could potentially serve as targets for therapeutic intervention. 2)In addition to the therapeutic strategies already known, some recent reports indicate new areas for the development of target selective drugs for the treatment of metastatic breast cancer.3) The earliest adjuvant chemotherapy, with singleagent alkylating and anti-metabolic drugs, was soon replaced by combination therapy, as it was demonstrated that simultaneous combination of two or more agents provided better results. 4,5) Kalpaamruthaa is a Siddha formulation, which has been formulated in our laboratory. They contain Semecarpus anacardium LINN. (SA), Emblica officinalis and honey with different ratio. Kalpaamruthaa (KA) is a Siddha preparation which has been formulated in our laboratory, the components studies of this drug reveals the presence of flavonoids, ascorbic acid, polyphenols, tannins, sugars and sterols. Flavonoids are seemingly more widely dispersed in the food supply and are of more varied composition than are isoflavones. For these reason, their absorption and metabolism have been less completely characterized. Cameron and Pauling 6) believed that ascorbic acid combats cancer by promoting collagen synthesis and thus prevents tumors from invading other tissues. Flavonoids are polyphenols widely distributed and known to possess biological and pharmacological activities, including anti-inflammatory action against free radicals. 7)Isoflavonoids are members of the broad class of plant polyphenols that have been shown in vivo to have benefit in the treatment of a wide variety of chronic diseases, including cancer. Another important consideration in vivo is the localized metabolism of isoflavones that may occur in the vicinity of tumor cells. Many experiments to verify the association between isoflavone intake and disease prevention have been reported. 8)The biochemical evaluation of glycoprotein components, marker enzymes and lysosomal enzymes of liver, kidney and blood of control and experimental rats was carried out to study the therapeutic efficacy of KA on 7,12-dimethylbenz-(a)anthracene (DMBA) induced mammary carcinoma bearing rats (Sprague-Dawley strain). This study was undertaken to arrive at the effective dose of KA in mammary carcinoma condition in rats. MATERIALS AND METHODS MaterialsMammary carcinoma was induced ...

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“…Numerous studies have reported increased expression, activity and/or altered cellular localization of individual cathepsins, in particular cysteine cathepsins, in human cancers. Increased levels of cathepsins B and H have been found in tumors of breast cancer patients, and cathepsin B tumor expression levels correlated positively with a poor prognosis (5)(6)(7)(8)(9)(10)(11). Cathepsin X has been studied far less in cancer, with only 2 studies reporting on its expression in tumors.…”

Section: Introductionmentioning

confidence: 99%

Cathepsin B, Cathepsin H, Cathepsin X and Cystatin C in Sera of Patients with Early-Stage and Inflammatory Breast Cancer

et al. 2008

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Numerous studies have linked cathepsins and their inhibitor cystatin C to tumor invasion and metastasis. We examined whether cathepsin B, cathepsin H, cathepsin X and cystatin C could be detected in sera from women with earlystage or inflammatory breast cancer and whether they correlated with clinicopathological characteristics. Preoperative serum was obtained from 176 patients with early-stage breast cancer (tumor size ≤5 cm, negative lymph nodes) and 31 patients with inflammatory breast cancer. Cathepsin and cystatin C levels were measured by ELISA. The patient and tumor characteristics under study were age at diagnosis, menopausal status, tumor size, tumor grade, and steroid hormone receptor status. Serum cathepsin B levels were significantly lower in patients with poorly differentiated tumors. High cystatin C levels were associated with tumor size, postmenopausal status and patient age. Interestingly, significantly lower levels of cathepsin X and H were found in patients with inflammatory breast cancer, a trend also observed for cathepsin B and cystatin C.

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Cathepsins D, B and L in Breast Carcinoma and in Transformed Human Breast Epithelial Cells (HBEC)

Cited by 33 publications

References 15 publications

Cathepsins D, B, and L in transformed human breast epithelial cells

Cathepsins D, B, and L in transformed human breast epithelial cells

Anticancer Effect of Kalpaamruthaa on Mammary Carcinoma in Rats with Reference to Glycoprotein Components, Lysosomal and Marker Enzymes

Cathepsin B, Cathepsin H, Cathepsin X and Cystatin C in Sera of Patients with Early-Stage and Inflammatory Breast Cancer

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