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Aromatic sulphur compounds from Allium species induce antioxidant signaling in human bladder cancer cells SL-31

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Trends in Natural Product Research – PSE Young Scientists’ Meeting Budapest, June 19th-21th, 2019

78

SL-31

doi: 10.14232/tnpr.2019.sl31

Aromatic sulphur compounds from Allium species induce antioxidant signaling in human bladder cancer cells

Emil Jivishov1,2*, Jörg Hänze3, Pietro Di Fazio4, Rainer Hofmann3, Shah Mahmoud Faqiri5 and Michael Keusgen1

1 Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, Philipps University of Marburg, Marburg, Germany

2 Department of Chemistry, Azerbaijani-French University (UFAZ-ASOIU), Baku, Azerbaijan

3 Department of Urology and Pediatric Urology, Philipps University of Marburg, Marburg, Germany

4 Department of Visceral, Thoracic and Vascular Surgery, Philipps University of Marburg, Marburg, Germany.

5 Department of Forestry, University of Balkh, Mazar-e Sharif, Afghanistan

*E-mail: emil.jivishov@ufaz.az

In this study, anticancer effect of ethyl acetate extracts from bulbs and flowers of 68 Allium species originated from Southwest Asia to the high mountains of Central Asia were analysed, with many of them being evaluated for the first time. The extracts were analysed dose dependently and compared to two pure known Allium compounds namely, 2,2′-dipyridyl disulphide and dipyrithione. Doxorubicin drug was used as a reference. Human bladder cancer cell lines T24 and UMUC3 were tested in comparison to non-cancer primary human foreskin fibroblasts (HFF). The most cytotoxic species were A. stipitatum (Afghanistan), and A. aflatunense with the LD50 values comparable to the doxorubicin’s LD50 value. Toxicity of the Allium extracts against human foreskin fibroblasts (HFF) cells was considerably higher than the toxicity of the doxorubicin. The extracts of A. stipitatum, A. aflatunense, and of other species were analysed for effects on cell death and cell cycle. The extracts caused a significant increase of the sub G1 events. Additionally, cyclin dependent kinase inhibitor (CDKN1A) was induced. Using bioassay guided fractionation, aromatic sulphur compounds from A. stipitatum and A. aflatunense extracts, were identified as active compounds acting as oxidative stress inducers. This suggestion was supported by the observation that the treated cells displayed enhanced antioxidant signaling pathway mediated by Nrf2 as indicated by enhanced HO-1 levels.

Acknowledgements

We thank Ekaterina Oplesch and Susanne Lingelbach for excellent technical assistance.

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