The Investigation of the Effects of Curcumin on SK-MEL-30 Human Melanoma Cell Line

Öz

The most aggressive form of skin cancer, melanoma, has a terrible prognosis its advanced stages due to treatments' limited efficacy and significant side effects. Curcumin has been shown to be effective against lesions in many cancer taypes such as colon, prostate, pancreas, liver and multiple myeloma. The aim of the study was to investigated the effects of curcumin on malign melanoma cells.In the present study we used SK-MEL – 30 human melanoma cell line. The cultured cells were incubated with different doses with te range of 2.5 μg, 6.75 μg, 12.5 μg, 15 μg and 25 μg curcumin for 24 and 48 hours. Annexin V/PI and caspase 3/7 kit analyzes were used to determine the cell survivial and apoptosis. Annexin V/PI analyzes was releaved that 25 μg dose of curcumin treatment decreased the melanoma cell survival approximately %50 for 48hours. Furthermore caspase3/7 experimental analyzes shown that the 25μg curcumin also induced the apoptosis for 48 hours. In conclusion in the present study we demonstrated antiproliferative and apoptotic effects of curcumin on melanoma cells. We can suggest that further research is required to determine the clinical effects of curcumin.

Anahtar Kelimeler

• annexin V/PI
• cancer
• caspase3/7
• curcumin
• SK-MEL – 30 human melanoma cell line

Kurkuminin SK-MEL-30 İnsan Melanoma Hücrelerine Etkisinin Araştırılması

Öz

Melanoma en agresif kanser türüdür ve tedavilerin yetersiz olmasından kaynaklı ileri aşamalarda kötü prognoz ile karakterizedir. Kurkuminin kolon, pankreas, prostat, karaciğer ve multipl miyelom dahil olmak üzere çeşitli kanserlerdeki lezyonlara karşı etkili olduğu kanıtlanmıştır. Bizde çalışmamızda kurkuminin malign melanoma hücrelerine etkisini araştırmayı amaçladık. Çalışmamızda SK-MEL – 30 insan melanoma hücre hattı kullanıldı. SK-MEL – 30 melanoma hücreleri kültüre edildikten sonra 2.5 μg, 6.75 μg, 12.5 μg, 15 ug ve 25 μg kurkumin ile 24 ve 48 saat süre ile inkübe edildi. Annexin V/PI ve Caspase 3/7 analizleri ile apoptoziz değerlendirildi. Annexin V/PI analizi sonucunda 25 μg kurkuminin 48 saat süre sonunda maling melanoma hücrelerinde yaklaşık %50 oranında canlılığı azalttığı tespit edildi.Bunlara ek olarak benzer şekilde Kaspase 3/7 analizi sonuçlarında da doz oranı arttıkça hücre ölümünün gerçekleştiği ve 25 μg kurkumin uygulamasının melanoma hücrelerinde apoptozu indükleyerek hücre ölümüne neden olduğu gösterildi. Sonuç olarak bu çalışma ile kurkuminin maling melanoma hücrelerine karşı antiproliferatif ve apoptozu indükleyici etkisi olduğu belirlendi. Kurkuminin klinik etkilerinin tespit edilebilmesi için daha kapsamlı çalışmaların yapılması gerektiğini önermekteyiz.

Anahtar Kelimeler

• annexin V/PI
• kanser
• kaspaz 3/7
• kurkumin
• SK-MEL–30 insan melanoma hücre hattı

Kaynakça

1. 1. Lellia D, Pedonea C, Sahebkarb A. Curcumin and treatment of melanoma: The potential role of microRNAs. Biomed Pharmacother 2017; 88: 832–834 88 (2017).
2. 2. Anand P, Kunnumakkara Ab, Newman Ra, Aggarwal Bb. Bioavailability of curcumin: problems and promises. Mol Pharm 2007; 4: 807-818.
3. 3. Shishodia S, Sethi G, Aggarwal BB. Curcumin: getting back to the roots. Ann N Y Acad Sci 2005;1056:206-17.
4. 4. Pari L, Tewas D, Eckel J. Role of curcumin in health and disease. Arch Physiol Biochem 2008;114(2):127-49
5. 5. Ushida J, Sugie S, Kawabata K et. al. Chemopreventive effect of curcumin on Nnitrosomethylbenzylamine- induced esophageal carcinogenesis in rats. Jpn J Cancer Res 2000; 91(9): 893-898.
6. 6. Cheng AL, Hsu CH, Lin JK. et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001; 21: 2895–2900.
7. 7. Sharma RA, McLelland HR, Hill KA. Et al.Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin. Cancer Res 2001; 7: 1894–1900
8. 8. Aggarwal BB, Shishodia S, Takada Y. Et al. Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice." Clin Cancer Res 2005; 11(20): 7490-7498.

9. 9. Aggarwal BB, Yuan W, Li S, Gupta SC. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric. Mol Nutr Food Res 2013; 57(9): 1529-1542.
10. 10. Kumar Mitra A, Krishna M. In vivo modulation of signaling factors involved in cell survival. J. Radiat. Res 2004; 45: 491–495.
11. 11. Depeille P, Cuq P, Passagne I, Evrard A, Vian L. Combined effects of GSTP1 and MRP1 in melanoma drug resistance. BJC 2005; 93, 216–223.
12. 12. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as Curecumin: fromkitchentoclinic, Biochem. Pharmacol 2008; 75(4), 787-809.
13. 13. Dilara D. Bitkisel Ve Antioksidan İçerikli Vital Pulpa Tedavi Ajanlarının Sitotoksisite Ve Alkalen Fosfataz Düzeylerinin Değerlendirilmesi (Doktora Tezi). İstanbul: İstanbul Üniversitesi; 2020.
14. 14. Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa M. Curcumin and Health. Molecules 2016; 21: 1–22.
15. 15. Bar-Sela G, EpelbaumR, Schaffer M, Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications.Curr. Med Chem 2010; 17: 190–197.
16. 16. Panahi Y, Saadat A, Beiraghdar F, SahebkarA. Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized double-blind placebo-controlled trial. Phytother Res 2014; 28: 1461–1467.
17. 17. Sahebkar A. Dual effect of curcumin in preventing atherosclerosis: the potential role of pro-oxidant-antioxidant mechanisms. Nat Prod Res 2015; 29: 491–492.
18. 18. Esmaily H, Sahebkar A, Iranshahi M, Ganjali S, Mohammadi A, Ferns G, Ghayour-Mobarhan M. An investigation of the effects of curcumin on anxiety and depression in obese individuals: A randomized controlled trial. Chin J Integr Med 2017;21: 332-338.
19. 19. Kunnumakkara AB, Bordoloi D, Harsha C, Banik K, Gupta SC, Aggarwal BB.Curcumin mediates anticancer effects by modulating multiple cell signaling pathways. Clin. Sci 2017; 131(15): 1781–1799.
20. 20. Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E.Chemopreventive and therapeutic effects of curcumin. Cancer Lett 2005; 223: 181-190.
21. 21. Aggarwal BB, Sundaram C, Malani N, Ichikawa H .Curcumin: The Indian solid gold. Adv Exp Med Biol 2007; 595:1–75.
22. 22. Manikandan PSM, Aishwarya S, Manohar BM, Lokanadam B, Puvanakrishnan R Curcumin modulates free radical quenching in myocardial ischaemia in rats. Int J Biochem Cell Biol 2004; 36:1967- 80.
23. 23. Beşir Er. Rasyona Katılan Kurkuminin İnsan Ovaryum Kanseri İçin Preklinik Bir Model Olan Yumurta Tavuklarında Bazı Apoptotik Markerlar Üzerine Etkileri. (Yüksek Lisans Tezi.) Fırat Üniversitesi Fen Bilimleri Enstitüsü; 2016.
24. 24. Prasad C P, Rath G, Mathur S, Bhatnagar D, Ralhan R. Potent growtsuppressive activity of curcumin in human breast cancer cells: Modulation of Wnt/β-catenin signaling. Chemico-biological interactions. 2009;181(2):263-71.
25. 25. Yu CX, Zhang XQ, Kang LD, Zhang PJ, Chen WW, Liu WW.Emodin induces apoptosis in human prostate cancer cell LNCaP. Asian J. Androl.2008;10(4):625-34.
26. 26. Tomatır AG. Apoptoz: Programlı Hücre Ölümü. Turk. Klin. J. Med. 2003;23(6):499-508.
27. 27. Eröz R, Alkoç OA, Baltacı D, Oktay M, Çolakoğlu S. Apoptozis Hakkında Bilinenler. Düzce Tıp Fak Derg 2012;14(2):87-101.
28. 28. Berta T, Qadri YJ, Chen G, Ji RR. Microglial Signaling in Chronic Pain with a Special Focus on Caspase 6, p38 MAP Kinase, and Sex Dependence, Journal of Dental Research 2016; 1–8.
29. 29. Cadena SG, Massieu L Caspases and their role in inflammation and ischemic neuronal death. Focus on caspase-12, Apoptosis 2016; 21,763–777.
30. 30. Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how manyways can curry kill tumor cells selectively? AAPS J. 2009;11(3):495-510.
31. 31. Zhu GH, Dai HP, Shen Q, et al. Curcumin induces apoptosis and suppresses invasion through MAPK and MMP signaling in human monocytic leukemia SHI- 1 cells. Pharm. Biol 2016; 54(8): 1303-1311
32. 32. Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 2003; 23(1A): 363-398.
33. 33. Yavuz Türel. Curcuma Longa (Zerdeçal) Bitkisinden Elde Edilen Kurkumin Etken Maddesinin Kolon Kanseri Hücre Hattı Üzerine Apoptotik Etkisinin Araştırılması. Doktora Tezi. Süleyman Demirel Üniversitesi Sağlık Bilimleri Enstitüsü Tıbbi Biyoloji Anabilim Dalı. Isparta – 2017