ESTRADIOL ENHANCES GOLD NANOPARTICLES INCORPORATION IN MCF-7 BREAST CANCER CELLS BY MODIFYING MEMBRANE ROUGHNESS

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 292-325-Breast & Prostate Cancer
Basic
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-309
Carlos Lara-Cruz*1, Javier E. Jiménez-Salazar1, Roberto C. Lazzarini-Lechuga1, Leticia González-Núñez1, Nikola Batina1, Eva Ramón-Gallegos2 and Pablo Damian-Matsumura1
1Universidad Autónoma Metropolitana (UAM), Mexico City, Mexico, 2National Polytechnic Institute (IPN) México, Mexico City, Mexico
Gold nanoparticles (AuNP) have been investigated in various contexts in relation to breast cancer diagnosis and treatment, including as a delivery vehicle for several chemotherapeutic agents. AuNP were recently investigated with regard to cytotoxicity and biocompatibility according to their interaction with cells, since variations in membrane roughness are possibly related for a successful therapy. In different cell models, it has been shown that estradiol (E2) can modulate significantly membrane fluidity; however, this subject has largely remained uninvestigated when incubated with AuNP. We detected changes in the morphology and physical properties of individual human breast cancer MCF-7 cells by atomic force microscopy (AFM) and visualized AuNP (20 nm) intracellular localization by confocal microscopy in the absence and presence of E2. MCF-7 cells were synchronized to the G0 stage of the cell cycle through serum deprivation techniques. AFM observations clearly showed changes in MCF-7 plasma membrane roughness, measured as RMSRq values, with  maximum effect observed after 12 hours of incubation with E2 (1 nM), which was precluded by the estrogen receptor (ER) blocker ICI 182780.  During the incubation with AuNP (20 nm; 80 μg/mL) in combination with E2, plasma membrane roughness RMSRq values increased significantly after 6 hours, compared to controls (P<0.005). Surprisingly, AuNP, in the presence of E2, were localized in the cytoplasm and very close to the nucleus even at 2 hours of incubation; meanwhile, in the absence of E2 this process took up to 12 hours. We confirmed that uptake and transport of the AuNP in breast cancer cells was mediated by lysosomes, since colocalization of AuNP and LysoTracker® Red was observed by confocal laser scanning microscopy, both in the absence and presence of E2. It is worth noting that AuNP exerted concentration-dependent MCF-7 cell cytotoxicity at 80 μg/mL and 72 hours of incubation, effect that was enhanced in the presence of E2. This newly revealed correlation between changes in plasma membrane roughness and increased AuNP uptake enhanced by the presence of E2 could provide new insight for combined nano-hormonotherapy in human breast cancer.

Nothing to Disclose: CL, JEJ, RCL, LG, NB, ER, PD

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Acknowledgments: This study was supported by DCBS/DCBI-UAM, the ICYTDF-UAM Nanotechnology project and CONACYT-MEXICO grant No: CB-2006-1-61242 (N. Batina). CL-C and JEJ-S are recipients of CONACYT's scholarships and are enrolled in the Experimental Biology Graduate Program, UAM, MEXICO. We are thankful for the technical support of the crew from the DCBS-UAM Laboratories of Confocal Microscopy (RC Lazzarini) and Molecular Biology (A. Serrato).