Polyamine pathway as a player in breast cancer cell proliferation in diabetic conditions

Abstract

Diabetes/hyperglycemia has been known to increase cancer cell proliferation, leading to metastasis and even mortality. High blood sugar is also known to reduce the effects of cancer therapeutics. Polyamines (spermine, spermidine, and putrescine) which are involved in several cellular processes such as cell growth, replication, and transcription, have been shown to be elevated in certain cancers including colon cancer and skin cancer. We hypothesized that polyamines are involved with proliferation of breast cancer cells in diabetic conditions. Cell lines used in this study included MCF‐7 (early stage breast cancer), MDA‐MB‐231 (late stage breast cancer), and MCF‐10A (normal breast epithelial cells). Cells were treated with normal glucose (NG, 5mM) or high glucose (HG, 25 mM) in the presence/absence of polyamine pathway inhibitors. Both MDA‐MB‐231 and MCF‐10A cells showed significant proliferation with HG treatment after 72 hr, which was not observed in MCF‐7 cells. Simultaneous treatment with an ornithine decarboxylase (polyamine synthesis enzyme) inhibitor, difluoromethylornithine (DFMO) could prevent this effect. Interestingly, while spermine levels were not altered with HG treatment in breast cancer cells (MCF‐7 and MDA‐MB‐231), they were significantly increased in MCF‐10A cells. This is possibly due to the fact that cancer cells have endogenously high levels of polyamines, such that further increase is prevented to avoid toxicity from polyamines. Nevertheless, DFMO was able to decrease spermine and spermidine levels induced with glucose treatments, suggesting a role of polyamine pathway in regulating growth. Putrescine levels were undetectable in all samples. In conclusion, polyamine pathway is involved with HG mediated normal breast epithelial cell and breast cancer cell proliferation. Future studies will involve further analysis of the mediators which regulate polyamine production.Support or Funding InformationUNK Faculty Start‐up Funds (SC); Undergraduate Research Fellowship Grant (CC and JO)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.