Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate

Metabolic Profiling of Epithelial Ovarian Cancer Cell Lines: Evaluation of Harvesting Protocols for Profiling Using Nmr Spectroscopy

“…However, it can already be stated here that they are in agreement with the SKOV-3-R cells showing several features of tumor-initiating cells (TICs) [23]. As the term implies, this subtype of tumor cells can particularly efficiently form new tumors (metastases) and are extremely resistant to chemotherapy; TICs are thus believed to be the cause of post-treatment relapses into metastatic and treatment-resistant disease [33,34].…”

“…A multitude of protocols have been reported in the literature, thoroughly reviewed by Leon et al [19], several of which recommend either harvesting with cold organic solvent (often MeOH) or by addition of water combined with rapid liquid nitrogen freezing. Therefore, these two inherently different approaches for harvesting were tested and evaluated based on reproducibility and ability to classify metabolite differences between a parental ovarian cancer cell line (SKOV-3) and a multiresistant sub-line (SKOV-3-R) [23]. Moreover, the objective was also to explore the development of chemoresistance in EOC by identifying significant differences in the polar metabolome between these cell lines.…”

“…Cell culture SKOV-3 cells and a resistant sub-line, SKOV-3-R (previously described in [23]) were cultured as adherent cells in cell culture plates (Sarstedt, Helsingborg, Sweden) at 37°C, in 5% CO 2 in RPMI-1640 medium containing 2 mM l-glutamine, supplemented with 5% fetal bovine serum and 1% penicillin-streptomycin (all from Nordic Biolabs AB, Täby, Sweden). SKOV-3 identity was validated using short tandem repeat analysis AmpFlSTR Identifiler™ kit (Applied Biosystems/Life Technologies, Stockholm, Sweden) and cultures were routinely tested for mycoplasma contamination.…”

“…In this study we develop a tailored and reliable protocol for NMR-based metabolomics of intracellular metabolites in tumor cells, here represented by the metastatic EOC cell line SKOV-3. This protocol was applied for metabolic profiling of the polar metabolome of the parental SKOV-3 cell line and a multiresistant sub-line (SKOV-3-R) established after long-term repeated cisplatin treatment [23]. Therefore, the objective was also to examine resistance-specific metabolic changes through a metabolomics approach by comparing the two cell lines in terms of the polar intracellular metabolome.…”

Novel Tumor Antigen-Specific Monoclonal Antibody-Based Immunotherapy to Eradicate Both Differentiated Cancer Cells and Cancer-Initiating Cells in Solid Tumors

“…Chemotherapeutic agents such as carboplatin, cisplatin, and 5-fluorouracil have been reported recently to induce hepatocellular, 67 colon, 68 and ovarian CIC states. 69 In addition, radiotherapy has been shown to reprogram differentiated cancer cells into induced breast or liver cancer CICs by reexpression of a set of stemness genes (OCT4, Sox2, Nanog, and Klf4 in breast and Sox2 and Oct3/4 in liver). 70,71 In line with the data available in the literature, our results ( Figure 4) demonstrate in vitro an increased ability of breast cancer cells treated with ionizing radiation to form spheres under hypoxic conditions.…”