Part I. Molecular and cellular characterization of high nitric oxide-adapted human breast adenocarcinoma cell lines

B. J. Vesper, A. Onul, G. K. Haines, G. Tarjan, J. Xue, K. M. Elseth, B. Aydogan, M. B. Altman, J. C. Roeske, W. A. Paradise, H. De Vitto, J. A. Radosevich

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


There is a lack of understanding of the casual mechanisms behind the observation that some breast adenocarcinomas have identical morphology and comparatively different cellular growth behavior. This is exemplified by a differential response to radiation, chemotherapy, and other biological intervention therapies. Elevated concentrations of the free radical nitric oxide (NO), coupled with the up-regulated enzyme nitric oxide synthase (NOS) which produces NO, are activities which impact tumor growth. Previously, we adapted four human breast cancer cell lines: BT-20, Hs578T, T-47D, and MCF-7 to elevated concentrations of nitric oxide (or high NO [HNO]). This was accomplished by exposing the cell lines to increasing levels of an NO donor over time. Significantly, the HNO cell lines grew faster than did each respective ("PARENT") cell line even in the absence of NO donor-supplemented media. This was evident despite each "parent" being morphologically equivalent to the HNO adapted cell line. Herein, we characterize the HNO cells and their biological attributes against those of the parent cells. Pairs of HNO/parent cell lines were then analyzed using a number of key cellular activity criteria including: cell cycle distribution, DNA ploidy, response to DNA damage, UV radiation response, X-ray radiation response, and the expression of significant cellular enzymes. Other key enzyme activities studied were NOS, p53, and glutathione S-transferase-pi (GST-pi) expression. HNO cells were typified by a far more aggressive pattern of growth and resistance to various treatments than the corresponding parent cells. This was evidenced by a higher S-phase percentage, variable radioresistance, and up-regulated GST-pi and p53. Taken collectively, this data provides evidence that cancer cells subjected to HNO concentrations become resistant to free radicals such as NO via up-regulated cellular defense mechanisms, including p53 and GST-pi. The adaptation to NO may explain how tumor cells acquire a more aggressive tumor phenotype.

Original languageEnglish
Pages (from-to)203-214
Number of pages12
JournalTumor Biology
Issue number1
StatePublished - Feb 2013
Externally publishedYes


  • Adenocarcinoma
  • Breast cancer
  • Nitric oxide (NO)
  • Nitric oxide synthase (NOS)
  • Reactive Nitrogen Species (RNS)
  • Reactive Oxygen Species (ROS)


Dive into the research topics of 'Part I. Molecular and cellular characterization of high nitric oxide-adapted human breast adenocarcinoma cell lines'. Together they form a unique fingerprint.

Cite this