Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells

Jabbar, Javaid; TÜRK, Seyhan; Ghasemi, Mehdi; Malkan, Umit Yavuz; okay, mufide; Haznedaroglu, Ibrahim C.; Hocaoglu, Helin

doi:10.4999/uhod.203965

Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells

Mehdi GHASEMI, (Lokman Hekim Üniversitesi, Tıp Fakültesi, Tıbbi Mikrobiyoloji Anabilim Dalı, Ankara, Türkiye)

Müfide OKAY, (Hacettepe Üniversitesi, Tıp Fakültesi, Hematoloji Anabilim Dalı, Ankara, Türkiye)

Ümit Yavuz MALKAN, (Sağlık Bilimleri Üniversitesi, Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Hematoloji Anabilim Dalı, Ankara, Türkiye)

Seyhan TÜRK, (Hacettepe Üniversitesi, Eczacılık Fakültesi, Biyokimya Anabilim Dalı, Ankara, Türkiye)

Javaid JABBAR, (Bilkent Üniversitesi, Moleküler Biyoloji ve Genetik Bölümü, Ankara, Türkiye)

Helin HOCAOGLU, (UTSouthwestern Üniversitesi, Fizyoloji Bölümü, Teksas, ABD)

İbrahim HAZNEDAROĞLU (Hacettepe Üniversitesi, Tıp Fakültesi, Hematoloji Anabilim Dalı, Ankara, Türkiye)

Uluslararası Hematoloji-Onkoloji Dergisi

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Yıl: 2020 Cilt: 30 Sayı: 1 Sayfa Aralığı: 43 - 53 Metin Dili: İngilizce DOI: 10.4999/uhod.203965 İndeks Tarihi: 06-11-2020

Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells

Öz:

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 involvedin oxidative phosphorylation [OXPHOS] pathway. ABS treatment has shown to increase the sensitivity of A2058 towards etoposideand 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 comparedtwo sets of melanoma cell lines; A375 with A2058 and A375 with SK-MEL-2. The clusters that we obtained from A375 and A2058comparison did contain mitochondrial related clusters, their corresponding p value was not significant. Whereas, the clusters fromA375 and SK-MEL-2 comparison contain 72 genes in ‘oxidoreductase’ cluster with enrichment score of 2.52. To get insight of theoxidoreductase cluster, we put the genes in that cluster to Enrichr. We found that majority of the genes among oxidoreductase clusterparticipate 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.

Anahtar Kelime:

Ankaferd Hemostat’ın Malign Melanom Hücrelerinde Etoposit Direncine Etkisi

Öz:

Kemoterapötik ilaçlara karşı direnç gelişimi, kanser tedavisinde bir engel haline gelmiştir. Ankaferd Hemostat’ın (ABS), melanom hücrelerinin proliferasyonunu baskıladığı gösterilmiştir; ancak mekanizması hakkında çok az şey bilinmektedir. Bu çalışmada, ABS’nin oksidatif fosforilasyon (OXPHOS) yolağında yer alan genleri değiştirerek, A2058 gibi bazı melanom hücre dizilerini etoposide karşı daha duyarlı hale getirilebileceğini gösterdik. Bu çalışmada, ABS tedavisinin A2058’in etoposide duyarlılığını arttırdığı gösterildi, ancak SKMEL-5 için herhangi bir etki gösterilemedi. Daha önce etoposide daha dirençli olduğu bilinen SK-MEL-30, bizim çalışmamızda ABS’ye karşı en az hassasiyet gösterdi. Analizimiz sonucunda, mitokondri kümelerinin ABS tarafından değiştirilen genlerle ilişkili olduğunu gördük. İddiamızı doğrulamak için iki set melanom hücre çizgisini (A375’i A2058 ile ve A375’i SK-MEL-2 ile) karşılaştırdık. A375 ve A2058 karşılaştırmasından elde ettiğimiz kümeler mitokondriyal ilişkili kümeler içermekteydi, ancak p değerleri anlamlı değildi. Öte yandan, A375 ve SK-MEL-2 karşılaştırmasından elde edilen kümeler, 2.52 zenginleştirme skoruna sahip ‘oksidoredüktaz’ kümesinde 72 gen içermekteydi. Oksidoredüktaz kümesini analiz etmek için, bu kümedeki genleri Enrichr’e koyduk. Oksidoredüktaz kümesi içindeki genlerin çoğunun oksidatif fosforilasyona ve elektron taşıma zincirine katıldığını bulduk. Sonuç olarak bu çalışma, etoposit tedavisinden önce ABS kullanımının, OXPHOS genlerinin değişmesi nedeniyle melanom hücre çizgilerinin tepkisini artırabileceğini öne sürmektedir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	Ghasemi M, okay m, Malkan U, TÜRK S, Jabbar J, Hocaoglu H, Haznedaroglu I (2020). Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. , 43 - 53. 10.4999/uhod.203965
Chicago	Ghasemi Mehdi,okay mufide,Malkan Umit Yavuz,TÜRK Seyhan,Jabbar Javaid,Hocaoglu Helin,Haznedaroglu Ibrahim C. Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. (2020): 43 - 53. 10.4999/uhod.203965
MLA	Ghasemi Mehdi,okay mufide,Malkan Umit Yavuz,TÜRK Seyhan,Jabbar Javaid,Hocaoglu Helin,Haznedaroglu Ibrahim C. Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. , 2020, ss.43 - 53. 10.4999/uhod.203965
AMA	Ghasemi M,okay m,Malkan U,TÜRK S,Jabbar J,Hocaoglu H,Haznedaroglu I Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. . 2020; 43 - 53. 10.4999/uhod.203965
Vancouver	Ghasemi M,okay m,Malkan U,TÜRK S,Jabbar J,Hocaoglu H,Haznedaroglu I Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. . 2020; 43 - 53. 10.4999/uhod.203965
IEEE	Ghasemi M,okay m,Malkan U,TÜRK S,Jabbar J,Hocaoglu H,Haznedaroglu I "Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells." , ss.43 - 53, 2020. 10.4999/uhod.203965
ISNAD	Ghasemi, Mehdi vd. "Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells". (2020), 43-53. https://doi.org/10.4999/uhod.203965

APA	Ghasemi M, okay m, Malkan U, TÜRK S, Jabbar J, Hocaoglu H, Haznedaroglu I (2020). Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. Uluslararası Hematoloji-Onkoloji Dergisi, 30(1), 43 - 53. 10.4999/uhod.203965
Chicago	Ghasemi Mehdi,okay mufide,Malkan Umit Yavuz,TÜRK Seyhan,Jabbar Javaid,Hocaoglu Helin,Haznedaroglu Ibrahim C. Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. Uluslararası Hematoloji-Onkoloji Dergisi 30, no.1 (2020): 43 - 53. 10.4999/uhod.203965
MLA	Ghasemi Mehdi,okay mufide,Malkan Umit Yavuz,TÜRK Seyhan,Jabbar Javaid,Hocaoglu Helin,Haznedaroglu Ibrahim C. Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. Uluslararası Hematoloji-Onkoloji Dergisi, vol.30, no.1, 2020, ss.43 - 53. 10.4999/uhod.203965
AMA	Ghasemi M,okay m,Malkan U,TÜRK S,Jabbar J,Hocaoglu H,Haznedaroglu I Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. Uluslararası Hematoloji-Onkoloji Dergisi. 2020; 30(1): 43 - 53. 10.4999/uhod.203965
Vancouver	Ghasemi M,okay m,Malkan U,TÜRK S,Jabbar J,Hocaoglu H,Haznedaroglu I Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells. Uluslararası Hematoloji-Onkoloji Dergisi. 2020; 30(1): 43 - 53. 10.4999/uhod.203965
IEEE	Ghasemi M,okay m,Malkan U,TÜRK S,Jabbar J,Hocaoglu H,Haznedaroglu I "Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells." Uluslararası Hematoloji-Onkoloji Dergisi, 30, ss.43 - 53, 2020. 10.4999/uhod.203965
ISNAD	Ghasemi, Mehdi vd. "Ankaferd Hemostat Affects Etoposide Resistance of the Malignant Melanoma Cells". Uluslararası Hematoloji-Onkoloji Dergisi 30/1 (2020), 43-53. https://doi.org/10.4999/uhod.203965