Antitumor Activity of NMS-P937 Specific Small-Molecule Polo-Like Kinase 1 Inhibitor, in PC3 Human Prostate Cancer, Hela Cervical Cancer, and SKOV-3 Ovarian Cancer Cell Lines

Abstract

Purpose: We aimed to investigate the antitumor activity of NMS-P937, a specific small-molecule polo-like kinase 1 (PLK1) inhibitor, in PC3 human prostate cancer, HeLa cervical cancer, and SKOV-3 ovarian cancer cell lines. Materials and methods: PC3, HeLa, and SKOV-3 cells were treated with NMS-P937 for 48 h. The viability was analyzed by XTT colorimetric assay. Since PC3 was found to be the most sensitive cell line, total oxidant status (TOS) values were evaluated in NMS-P937-treated and non-treated PC3 cells via TOS assay. Results: The proliferation of cancer cell lines was moderately inhibited by NMS-P937 in conjunction with the increase in concentration. The IC50 values of NMS-P937 in PC3, HeLa, and SKOV-3 cells were recorded as 27.3, 69.7, and 79.3 μM, respectively, for 48 h. TOS was measured in control and NMS-P937-treated PC3 cells and calculated as 3.15±0.36 and 4.49±0.64 μmol H2O2 Equiv./L, respectively, indicating the increased oxidative stress under the influence of the study compound (p=0.035). Conclusion: The PLK1 inhibitor NMS-P937 reduces the activity of cancer cell lines consisting of PC3 human prostate cancer, HeLa cervical cancer, and SKOV-3 ovarian cancer in a dose-dependent manner. This compound increases oxidative stress, which may play a pivotal role in the cytotoxic activity of the compound in PC3 cells. However, there is still a need to carry out both in vitro and in vivo studies, including different cancer cell lines and tumor models, and to reveal the adverse effects that may develop.

Keywords

• cancer cell lines
• cytotoxicity
• NMS-P937
• PLK1 inhibition
• oxidative stress

PC3 Insan Prostat Kanseri, Hela Servikal Kanser ve SKOV-3 Over Kanseri Hücre Hatlarında, Spesifik Küçük Moleküllü Polo Benzeri Kinaz 1 Inhibitörü NMS-P937'nin Antitümör Aktivitesi

Abstract

Amaç: Spesifik küçük molekül polo benzeri kinaz 1 (PLK1) inhibitörü olan NMS-P937'nin PC3 insan prostat kanseri, HeLa servikal kanser ve SKOV-3 over kanseri hücre hatlarında antitümör aktivitesini araştırmayı amaçladık. Araçlar ve Yöntem: PC3, HeLa ve SKOV-3 hücreleri, 48 saat boyunca NMS-P937 ile muamele edildi. Canlılık, XTT kolorimetrik tahlil ile analiz edildi ve PC3'ün en hassas hücre dizisi olduğu bulunduğundan, toplam oksidan status (TOS) değerleri, NMS-P937 ile tedavi edilmiş ve edilmemiş PC3 hücrelerinde TOS tahlili ile değerlendirildi. Bulgular: Kanser hücre hatlarının proliferasyonu, konsantrasyondaki artışla bağlantılı olarak NMS-P937 tarafından orta derecede inhibe edildi. NMS-P937'nin PC3, HeLa ve SKOV-3 hücrelerindeki 48s IC50 değerleri 27.3, 69.7 ve 79.3 μM olarak kaydedildi. TOS, kontrol ve NMS-P937 ile muamele edilmiş PC3 hücrelerinde ölçüldü ve sırasıyla 3.15±0.36 ve 4.49±0.64 μmol H2O2 Equiv./L olarak hesaplandı, bu da çalışma bileşiğinin etkisi altında artan oksidatif stresi gösterdi (p=0.035). Sonuç: PLK1 inhibitörü NMS-P937, PC3 insan prostat kanseri, HeLa servikal kanser ve SKOV-3 over kanserinden oluşan kanser hücre hatlarının aktivitesini doza bağlı bir şekilde azaltır. Bu bileşik oksidatif stresi arttırır ve bu da bileşiğin PC3 hücrelerinde sitotoksik aktivitesinde çok önemli bir rol oynayabilir. Ancak yine de farklı kanser hücre dizileri ve tümör modellerini içeren hem in vitro hem de in vivo çalışmaların yapılmasına ve gelişebilecek olumsuz etkilerin ortaya çıkarılmasına ihtiyaç vardır.

Keywords

• PLK1 inhibisyonu
• NMS-P937
• kanser hücre hatları
• sitotoksisite
• oksidatif stres

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