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Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design

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  • Joan J. Soldevila-Barreda

    (University of Warwick)

  • Isolda Romero-Canelón

    (University of Warwick)

  • Abraha Habtemariam

    (University of Warwick)

  • Peter J. Sadler

    (University of Warwick)

Abstract

Organometallic complexes are effective hydrogenation catalysts for organic reactions. For example, Noyori-type ruthenium complexes catalyse reduction of ketones by transfer of hydride from formate. Here we show that such catalytic reactions can be achieved in cancer cells, offering a new strategy for the design of safe metal-based anticancer drugs. The activity of ruthenium(II) sulfonamido ethyleneamine complexes towards human ovarian cancer cells is enhanced by up to 50 × in the presence of low non-toxic doses of formate. The extent of conversion of coenzyme NAD+ to NADH in cells is dependent on formate concentration. This novel reductive stress mechanism of cell death does not involve apoptosis or perturbation of mitochondrial membrane potentials. In contrast, iridium cyclopentadienyl catalysts cause cancer cell death by oxidative stress. Organometallic complexes therefore have an extraordinary ability to modulate the redox status of cancer cells.

Suggested Citation

  • Joan J. Soldevila-Barreda & Isolda Romero-Canelón & Abraha Habtemariam & Peter J. Sadler, 2015. "Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design," Nature Communications, Nature, vol. 6(1), pages 1-9, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7582
    DOI: 10.1038/ncomms7582
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    Cited by:

    1. Feng Gao & Guangyu Liu & Aobo Chen & Yangguang Hu & Huihui Wang & Jiangyuan Pan & Jinglei Feng & Hongwei Zhang & Yujie Wang & Yuanzeng Min & Chao Gao & Yujie Xiong, 2023. "Artificial photosynthetic cells with biotic–abiotic hybrid energy modules for customized CO2 conversion," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Hanchen Zhang & Nicolás Montesdeoca & Dongsheng Tang & Ganghao Liang & Minhui Cui & Chun Xu & Lisa-Marie Servos & Tiejun Bing & Zisis Papadopoulos & Meifang Shen & Haihua Xiao & Yingjie Yu & Johannes , 2024. "Tumor-targeted glutathione oxidation catalysis with ruthenium nanoreactors against hypoxic osteosarcoma," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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