International Journal of Hematology and Oncology 2021, Vol 31, Num 1 Page(s): 043-053
Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells

Mehdi GHASEMI1, Mufide OKAY2, Umit Yavuz MALKAN3, Seyhan TURK4, Javaid JABBAR5, Helin HOCAOGLU6, Ibrahim Celalettin HAZNEDAROGLU2

1Lokman Hekim University, Faculty of Medicine, Department of Medical Microbiology, Ankara, TURKEY
2Hacettepe University, School of Medicine, Department of Hematology, Ankara, TURKEY
3University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Department of Hematology, Ankara, TURKEY
4Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, Ankara, TURKEY
5Bilkent University, Department of Molecular Biology and Genetics, Ankara, TURKEY
6UTSouthwestern University, Department of Physiology, Texas, USA

Keywords: Ankaferd hemostat, Etoposide, Oxidative phosphorylation, Melanoma, Drug sensitivity
The development of resistance towards chemotherapeutic drugs has become an obstacle in treatment of cancer. Ankaferd Hemostat [ABS] has shown to suppress the proliferation of melanoma cells, but little is known about its’ mechanism. In this study, we demonstrate that ABS can make some melanoma cell lines such as A2058 more sensitive towards etoposide by altering the genes involved in oxidative phosphorylation [OXPHOS] pathway. ABS treatment has shown to increase the sensitivity of A2058 towards etoposide and showed no effect for SK-MEL-5. Previously known to be more resistant to etoposide, SK-MEL-30 showed least amount of sensitivity to ABS. We found mitochondrion cluster to be the most relevant to genes altered by ABS. To validate our claim, we compared two sets of melanoma cell lines; A375 with A2058 and A375 with SK-MEL-2. The clusters that we obtained from A375 and A2058 comparison did contain mitochondrial related clusters, their corresponding p value was not significant. Whereas, the clusters from A375 and SK-MEL-2 comparison contain 72 genes in ‘oxidoreductase’ cluster with enrichment score of 2.52. To get insight of the oxidoreductase cluster, we put the genes in that cluster to Enrichr. We found that majority of the genes among oxidoreductase cluster participate in oxidative phosphorylation and electron transport chain. Our study suggests that the use of ABS prior to etoposide treatment can increase the response of melanoma cell lines because of the alteration of OXPHOS genes.