Investigation of the potential anticancer effects of napelline and talatisamine dirterpenes on experimental brain tumor

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ORIGINAL ARTICLE

Investigation of the potential anticancer effects of napelline and talatisamine dirterpenes on experimental brain tumor models Merve Demirbag˘ Karaali . Elanur Aydın Karatas¸

Received: 3 January 2019 / Accepted: 31 May 2020 Ó Springer Nature B.V. 2020

Abstract Brain cancers are one of the most aggressive tumours in humans. Especially, gliomas are among the deadliest of human cancers and show highresistance to chemotherapeutic agents. On the other hand, discovery of biologically effective nonsynthetic biomaterials in treatments of different diseases, especially cancer, has continued to be one of the most popular research topics today. Therefore, we aimed to investigate biochemical, cytological and molecular genetic effects of napelline and talatisamine diterpenes in human U-87 MG glioma cells by using total antioxidant status and total oxidative status, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxphenyl)-2-(4-sulfophenyl)-2H-tetrozolium, inner salt and lactate dehydrogenase release assay and RT2 Prolifer PCR Arrays. Our results revealed that napelline and talatisamine exhibited cytotoxic effects at high doses. Napelline and talatisamine diterpenes increased apoptosis compared to control in U-87 MG cells. While napelline induced up-regulation of 50 and down-regulation of 13 genes, talatisamine induced upregulation of 32 and down-regulation of 18 genes in U-87 MG cells. Napelline was shown to have a higher anticancer activity than talatisamine. We think that,

M. Demirbag˘ Karaali (&)  E. Aydın Karatas¸ Faculty of Science, Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum, Turkey e-mail: [email protected]; [email protected]

napelline and talatisamine might be evaluated as potential chemotherapeutic agents for treatment of glioblastoma. Keywords Glioblastoma multiforme  Diterpenes  Anticancer activity  Cytotoxicity  Apoptosiz

Introduction Cancer is one of most common deadly diseases in today’s World (Peer et al. 2007). Deadly cancer types differ depending on age, gender and race (Anassi and Ndefo 2011). Brain cancers (gliomas, neuroblastoma, medullablastoma) are among devastating solid neoplasms that occur in mainly childhood and adults (Lawrence et al. 2014). Brain tumors are classified as primary or secondary brain tumors. Primary malignant brain tumors affect about 200,000 people annually worldwide and their incidence is rapidly increasing (Lee et al. 2010; Kheirollahi et al. 2015). Glioblastoma multiforme (GBM) is one of the most deadly and common brain tumors in adulthood (Idbaih et al. 2015). GBM is the most lethal form of gliomas, has a highly variable histopathology, as can be understood from the term ‘‘multiforme’’ (Stupp et al. 2005). GBM, generally occur in adults older than 40 years of age and the incidence in men is higher than women (JhanwarUniyal et al. 2015). It gives symptoms within an average of 6 months (Markett et al. 2005). The primary

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Cytotechnology

approach used