A MALDI-MS-based quantitative analytical method for endogenous estrone in human breast cancer cells

• Published in: Scientific reports 2016-04, Vol.6 (1), p.24489-24489, Article 24489
• Main Authors: Kim, Kyoung-Jin, Kim, Hee-Jin, Park, Han-Gyu, Hwang, Cheol-Hwan, Sung, Changmin, Jang, Kyoung-Soon, Park, Sung-Hee, Kim, Byung-Gee, Lee, Yoo-Kyung, Yang, Yung-Hun, Jeong, Jae Hyun, Kim, Yun-Gon
• Format: Article
• Language: English
• Subjects: 101/47; 14/10; 631/67/1857; 631/92/555; Aromatase; Aromatase Inhibitors - administration & dosage; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Estrogens; Estrogens - isolation & purification; Estrogens - metabolism; Estrone; Estrone - isolation & purification; Estrone - metabolism; Female; Humanities and Social Sciences; Humans; Mass spectroscopy; MCF-7 Cells; Metabolites; Metabolomics; multidisciplinary; Quantitation; Science; Science (multidisciplinary); Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep24489

The level of endogenous estrone, one of the three major naturally occurring estrogens, has a significant correlation with the incidence of post-menopausal breast cancer. However, it is challenging to quantitatively monitor it owing to its low abundance. Here, we develop a robust and highly sensitive mass-assisted laser desorption/ionization mass spectrometry (MALDI-MS)-based quantitative platform to identify the absolute quantities of endogenous estrones in a variety of clinical specimens. The one-step modification of endogenous estrone provided good linearity (R 2  > 0.99) and significantly increased the sensitivity of the platform (limit of quantitation: 11 fmol). In addition, we could identify the absolute amount of endogenous estrones in cells of the breast cancer cell line MCF-7 (34 fmol/10 6 cells) by using a deuterated estrone as an internal standard. Finally, by applying the MALDI-MS-based quantitative method to endogenous estrones, we successfully monitored changes in the metabolic expression level of estrones (17.7 fmol/10 6 letrozole-treated cells) in MCF-7 cells resulting from treatment with an aromatase inhibitor. Taken together, these results suggest that this MALDI-MS-based quantitative approach may be a general method for the targeted metabolomics of ketone-containing metabolites, which can reflect clinical conditions and pathogenic mechanisms.