Detection of polyol accumulation in a new ovarian carcinoma cell line, CABA I: a1H NMR study

Abstract

Ovarian carcinomas represent a major form of gynaecological malignancies, whose treatment consists mainly of surgery and chemotherapy. Besides the difficulty of prognosis, therapy of ovarian carcinomas has reached scarce improvement, as a consequence of lack of efficacy and development of drug-resistance. The need of different biochemical and functional parameters has grown, in order to obtain a larger view on processes of biological and clinical significance. In this paper we report novel metabolic features detected in a series of different human ovary carcinoma lines, by 1 H NMR spectroscopy of intact cells and their extracts. Most importantly, a new ovarian adenocarcinoma line CABA I, showed strong signals in the spectral region between 3.5 and 4.0 p.p.m., assigned for the first time to the polyol sorbitol (39+11 nmol/10 6 cells). 13 C NMR analyses of these cells incubated with [1-13 C]-D-glucose demonstrated labelled-sorbitol formation. The other ovarian carcinoma cell lines (OVCAR-3, IGROV 1, SK-OV-3 and OVCA432), showed, in the same spectral region, intense resonances from other metabolites: glutathione (up to 30 nmol/10 6 cells) and myo-inositol (up to 50 nmol/10 6 cells). Biochemical and biological functions are suggested for these compounds in human ovarian carcinoma cells, especially in relation to their possible role in cell detoxification mechanisms during tumour progression.

Abnormal Choline Phospholipid Metabolism in Breast and Ovary Cancer:Molecular Bases for Noninvasive Imaging Approaches

“…Recent analyses by Yoshimoto et al [62] showed 1.5-to 4.0-fold increases in the average [ 14 C]-Cho uptake by a wide variety of cancer cells as compared to non-tumoral fibroblasts, with a radiolabel distribution mainly confined (within 45 min) to water-soluble choline metabolites. In fact, 14 C-PC reached, in this time window, levels lower than 5% of the total pool of 14 C-labeled compounds. Moreover, [ 14 C]-Cho uptake correlated with Chok activity and with [ 3 H]-thymidine incorporation (a well known index of cell proliferation).…”

“…In particular, an increase in the 1 H-MRS resonance at 3.2 parts per million (ppm), arising from the trimethylammonium headgroups of the total pool of water-soluble choline-containing metabolites (tCho), has been reported as the most common feature in a large variety of cancers such as breast [6][7][8], prostate [9,10] and colon carcinomas [11], bone and soft tissue malignant lesions [12] and high-grade neuroepithelial tumors [13]. More recently, we also focused attention on alterations of the tCho spectral profile in human epithelial ovarian cancer (EOC) cells [14,15], an aspect which received only scarce attention in the past. Our studies showed that EOC cells represent a particularly suitable model to investigate the molecular bases of aberrant choline phospholipid metabolism associated with progression of tumors of epithelial origin [15].…”

Carbohydrate Chelation in Neutral Aqueous Solution: The threo‐Tetritolato‐Pd4 Butterfly Motif

“…On the one hand, polyols exist in the environment of administered platinumbased drugs: the hexitol sorbitol, for example, has been detected in tumour tissue at an increased level. [19] On the other hand, oligonuclear m-hydroxido-platinum cations need a substantially longer period of time for their formation than their Pd II counterparts due to the greater inertness of Pt II centres, possibly too long a period to be physiologically relevant. Experiments to clarify the basics of this chemistry are in progress.…”

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

“…Increased activity of the polyol pathway was also reported in other liver diseases such as Wilson's disease that is characterized by copper accumulation in the liver and other organs [81]. Activation of the polyol pathway was also reported in ovarian and cervical cancer cell lines [82,83], lung tumors [75], and colon [75,84], breast, ovary, cervix, and rectum cancers [85]. Recently, the sugar alcohol maltitol was studied as imaging contrast agent in brain tumors [86].…”