Effect of a New Sapogenol Derivative (AG-07) on Cell Death via Necrosis

Bildiriler > Tam Metin Bildiri · 2017

Yazarlar: YALÇIN ERZURUMLU, özgür tağ, Sinem YILMAZ, ERDAL BEDİR, Petek BALLAR KIRMIZIBAYRAK

Proceedings of the 2nd International Conference on Natural Products for Cancer Prevention and Therapy, Uluslararası, Sözlü Sunum, Tam Metin Bildiri, 2017-2017, cilt 1, ss 996-996

DOI: 10.3390/proceedings1100996

Özet

Saponins, plant secondary metabolites with high molecular weight, carry sugar groups on the triterpenic or steroidal skeleton. They exhibit biological activities such as anti-HIV, immunoadjuvant, analgesic and anticancer. Saponins have been reported to induce apoptosis, autophagy, stress responses and also inhibit cell cycle and invasion-migration in cancer cells. As saponins have partially weaker anti-cancer properties, they are often used as starting compounds for semi-synthesis of biologically more active molecules. With the same aim, we have focused on cycloartane-type saponins from Astragalus species to prepare potent compounds with cytotoxic activity. Cycloastragenol, a major sapogenol encountered only in Astragalus genus, was used to synthesize astragenol (AG) and then AG-07, a novel compound. Herein, we report the anticancer activities of AG and AG-07 against HCC1937 and HeLa cells by WST-1 assay. Additionally, levels of proteins associated with cell death are examined by immunoblotting. Cell death was also evaluated using flow cytometry and AO/EB staining. In comparison to AG, our results show that AG-07 is more cytotoxic. Furthermore, it induces formation of necrosis-associated protein fragments and necrosis-mediated cell death. In conclusion, AG-07, has a lethal effect on cancer cells through non-apoptotic cell death mechanism.

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