Lipid-peroxidation-resistant cell line for studying ferroptosis

This technology describes a cell line that overexpresses glutathione peroxidase 4, making it resistant to lipid peroxidation and consequently ferroptosis.

Unmet Need: In vitro model of ferroptosis for research and drug development

Ferroptosis is a unique form of programmed cellular death which is dependent on cellular iron and the accumulation of lipid-based reactive oxygen species, particularly lipid hydroperoxides, making the process peroxidation-dependent. This process has been implicated in a diverse array of cancers and degenerative diseases, emphasizing its utility as a potential drug target for treatment of various diseases. However, the mechanism behind tumor sensitivity to ferroptosis is not well understood, and there is currently no high-throughput, robust method for screening potential therapeutics targeting this pathway.

The Technology: Cell model of ferroptosis resistance

This technology is an engineered cell line which is resistant to lipid peroxidation, and subsequently ferroptosis. Glutathione peroxidase 4 (GPX4) is a lipid repair enzyme that prevents ferroptosis by preventing lipid peroxidation. Therefore, overexpression of this protein results in cells that are resistant to lipid peroxidation, which consequently are resistant to ferroptosis. As such, this cell line can be used for studying the effects of compounds and factors that drive ferroptosis. By pairing this cell line with its parental version, it is possible to determine which compounds, genes and other factors act in a lipid-peroxidation-dependent manner.

Applications:

• In vitro model for studying ferroptosis
• Drug screening to identify ferroptosis-inducing agents
• Genetic screening to identify ferroptosis-inducing genes
• Facilitate the development of animal models for studying ferroptosis

Advantages:

• High-throughput screening
• Compatible with various imaging modalities
• Applicable to various cancers
• Cost-effective

Lead Inventor:

Brent Stockwell, Ph.D.

Related Publications:

• Gaschler MM, Andia AA, Liu H, Csuka JM, Hurlocker B, Vaiana CA, Heindel DW, Zuckerman DS, Bos PH, Reznik E, Ye LF, Tyurina YY, Lin AJ, Shchepinov MS, Chan AY, Peguero-Pereira E, Fomich MA, Daniels JD, Bekish AV, Shmanai VV, Kagan VE, Mahal LK, Woerpel KA, Stockwell BR. “FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation” Nat Chem Biol. 2018 May; 14(5): 507-515.

• Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB, Brown LM, Girotti AW, Cornish VW, Schreiber SL, Stockwell BR. “Regulation of ferroptotic cancer cell death by GPX4” Cell. 2014 Jan 16; 156(1-2): 317-331.

• Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR. “Ferroptosis: an iron-dependent form of nonapoptotic cell death” Cell. 2012 May 25; 149(5): 1060-72.

Tech Ventures Reference:

• IR CU20193

• Licensing Contact: Beth Kauderer