A synergic approach to enhance long-term culture and manipulation of MiaPaCa-2 pancreatic cancer spheroids

Tumour spheroids have the potential to be used as preclinical chemo-sensitivity assays. However, the production of three-dimensional (3D) tumour spheroids remains challenging as not all tumour cell lines form spheroids with regular morphologies and spheroid transfer often induces disaggregation. In the field of pancreatic cancer, the MiaPaCa-2 cell line is an interesting model for research but it is known for its difficulty to form stable spheroids; also, when formed, spheroids from this cell line are weak and arduous to manage and to harvest for further analyses such as multiple staining and imaging. In this work, we compared different methods (i.e. hanging drop, round-bottom wells and Matrigel embedding, each of them with or without methylcellulose in the media) to evaluate which one allowed to better overpass these limitations. Morphometric analysis indicated that hanging drop in presence of methylcellulose leaded to well-organized spheroids; interestingly, quantitative PCR (qPCR) analysis reflected the morphometric characterization, indicating that same spheroids expressed the highest values of CD44, VIMENTIN, TGF-β1 and Ki-67. In addition, we investigated the generation of MiaPaCa-2 spheroids when cultured on substrates of different hydrophobicity, in order to minimize the area in contact with the culture media and to further improve spheroid formation

The Anticancer Effects of S-Adenosylmethionine on Breast Cancer Cells

S-Adenosyl-L-methionine (AdoMet) is a naturally-occurring sulfonium compound found in almost every tissue and fluid in the body that plays a central role in cellular metabolism. AdoMet, indeed, is the link to three key metabolic pathways: polyamine synthesis, transmethylation and transsulfuration. Literature and clinical studies regarding the AdoMet physiologic and physio-pathological roles underline its therapeutic potential to treat alcoholic liver disease, depression and joint pain. In recent years, several new metabolic functions have been assigned to this important and widely occurring sulfonium compound that exerts pleiotropic effects on signal transduction in many and different cell-types. In the last decade a lot of in vitro and in vivo studies highlighted the anti-proliferative, anti-metastatic and pro-apoptotic effects of AdoMet in cancer cells. In this review we summarize the most recent studies focusing on the anticancer effect of AdoMet in breast cancer cells and provide information on the broad spectrum of mechanistic actions underlying the antitumor effect of this physiological sulfonium compound. Our data on the synergistic effects of AdoMet with conventional therapeutic drugs appear to be clinically relevant and disclose a new scenario of intervention in which this natural and safe molecule, alone or in combination with other chemotherapy drugs could be utilized for the development of novel promising therapeutic strategies for the treatment of breast cancer