Melatonin receptors increase Momordica’s anticancer effects against PC-3 and HT-29

Öz

Aim: The aim of our study is to the evaluation of melatonin (MLT) and Momordica charantia (MC) combination on PC-3 and HT-29 cancer lines and to address the question of where or not MLT increases MC antitumor effect in the PC-3 and HT-29 cancer lines. Material and Method: The PC-3 and HT-29 cell lines were grown in a manufacturer-specified culture medium. Cisplatin, MLT, increasing concentrations of MC, 40 μg/ml MLT + increasing concentrations MC were applied to PC-3 and HT-29 cell lines for 72 hours. 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) cell viability, Total Antioxidant Capacity (TAC), Total Oxidant Status (TOS), Cellular Migration (Wound Healing test), and Lactate Dehydrogenase (LDH) tests were done 72 hours after drug administration. Results: The combination of MLT 40 μg/ml + MC 100 µg/ml reduced cell viability in both PC-3 and HT-29 cells. Besides, TAC and TOS levels showed a correlation with LDH and MTT assays and were found to be statistically significant (P<0.05). Also, it was observed in the migration test that the wound line widened in our combination groups from the 24th hours. However, it was observed that it only prevented migration at 72nd hours in pure groups. Conclusion: The combination of 40 μg/ml MLT with MC increased the antitumor effect compared to MC alone and reduced the viability of cancer cells more effectively than MC alone. So, MLT + MC treatment combination can be a new resource of therapeutics.

Anahtar Kelimeler

• HT-29
• LDH
• Melatonin
• Momordica
• PC-3

Melatonin reseptörleri PC-3 ve HT-29'a karşı Momordica'nın antikanser etkilerini artırır

Öz

Amaç: Çalışmamızın amacı, PC-3 ve HT-29 kanser hatlarında melatonin (MLT) ve Momordica charantia (MC) kombinasyonunun değerlendirilmesi ve MLT'nin PC-3 ve HT-29 kanser hatlarında MC antitümör etkisini nerede artırdığı sorusunu ele almaktır. Gereç ve yöntem: PC-3 ve HT-29 hücre çizgileri, üreticinin belirlediği bir kültür ortamında büyütüldü. Sisplatin, MLT, artan MC konsantrasyonları, MLT 40 μg / ml + artan konsantrasyonlar MC, PC-3 ve HT-29 hücre hatlarına 72 saat süreyle uygulandı. 3- (4,5-Dimetiltiyazol-2-Yl) -2,5-Difeniltetrazolyum Bromür (MTT) hücre canlılığı, Toplam Antioksidan Kapasitesi (TAC), Toplam Oksidan Durumu (TOS), Hücresel Göç (Yara İyileştirme testi) ve Laktat Dehidrojenaz (LDH) testleri, ilaç uygulamasından 72 saat sonra yapıldı. Bulgular: MLT 40 ug / ml + MC 100 ug / ml kombinasyonu, hem PC-3 hem de HT-29 hücrelerinde hücre canlılığını azalttı. Ayrıca TAC ve TOS seviyeleri LDH ve MTT testleri ile korelasyon gösterdi ve istatistiksel olarak anlamlı bulundu (P <0.05). Ayrıca migrasyon testinde kombinasyon gruplarımızda 24. saatten itibaren yara hattının genişlediği gözlendi. Ancak saf gruplarda göçü sadece 72. saatte engellediği görülmüştür. Sonuç: 40 ug / ml MLT'nin MC ile kombinasyonu, tek başına MC'ye kıyasla antitümör etkisini arttırdı ve kanser hücrelerinin canlılığını tek başına MC'den daha etkili bir şekilde azalttı. Dolayısıyla, MLT + MC tedavi kombinasyonu yeni bir terapötik kaynak olabilir.

Anahtar Kelimeler

• HT-29
• LDH
• Melatonin
• Momordica
• PC-3

Kaynakça

1. 1. Jemal, A., Global Cancer Statistics (vol 61, pg 69, 2011). Ca-a Cancer Journal for Clinicians, 2011. 61(2): p. 134-134.
2. 2. Knudsen, B.S. and V. Vasioukhin, Mechanisms of Prostate Cancer Initiation and Progression. Advances in Cancer Research, Vol 109, 2010. 109: p. 1-50.
3. 3. Sandhu, G.S. and G.L. Andriole, Overdiagnosis of prostate cancer. J Natl Cancer Inst Monogr, 2012. 2012(45): p. 146-51.
4. 4. Slattery, M.L., Diet, lifestyle, and colon cancer. Semin Gastrointest Dis, 2000. 11(3): p. 142-6.
5. 5. Torre, L.A., et al., Global cancer statistics, 2012. CA Cancer J Clin, 2015. 65(2): p. 87-108.
6. 6. Aklilu, M. and C. Eng, The current landscape of locally advanced rectal cancer. Nat Rev Clin Oncol, 2011. 8(11): p. 649-59.
7. 7. Hanahan, D. and R.A. Weinberg, Hallmarks of cancer: the next generation. Cell, 2011. 144(5): p. 646-74.
8. 8. Braun-Falco, M., et al., [Follicular drug reaction from cetuximab: a common side effect in the treatment of metastatic colon carcinoma]. Hautarzt, 2006. 57(8): p. 701-4.

9. 9. Jia, S., et al., Recent Advances in Momordica charantia: Functional Components and Biological Activities. Int J Mol Sci, 2017. 18(12).
10. 10. Raza, H., et al., Modulation of xenobiotic metabolism and oxidative stress in chronic streptozotocin-induced diabetic rats fed with Momordica charantia fruit extract. J Biochem Mol Toxicol, 2000. 14(3): p. 131-9.
11. 11. Grover, J.K. and S.P. Yadav, Pharmacological actions and potential uses of Momordica charantia: a review. J Ethnopharmacol, 2004. 93(1): p. 123-32.
12. 12. Yodkeeree, S., S. Garbisa, and P. Limtrakul, Tetrahydrocurcumin inhibits HT1080 cell migration and invasion via downregulation of MMPs and uPA. Acta Pharmacol Sin, 2008. 29(7): p. 853-60.
13. 13. de Almeida Chuffa, L.G., et al., Mitochondrial functions and melatonin: a tour of the reproductive cancers. Cell Mol Life Sci, 2019. 76(5): p. 837-863.
14. 14. Calastretti, A., et al., Melatonin Analogue Antiproliferative and Cytotoxic Effects on Human Prostate Cancer Cells. Int J Mol Sci, 2018. 19(5).
15. 15. Eck-Enriquez, K., et al., Pathways through which a regimen of melatonin and retinoic acid induces apoptosis in MCF-7 human breast cancer cells. Breast Cancer Research and Treatment, 2000. 61(3): p. 229-239.
16. 16. Winczyk, K., M. Pawlikowski, and M. Karasek, Melatonin and RZR/ROR receptor ligand CGP 52608 induce apoptosis in the murine colonic cancer. Journal of Pineal Research, 2001. 31(2): p. 179-182.
17. 17. Toubi, E. and Y. Shoenfeld, Protective autoimmunity in cancer (Review). Oncology Reports, 2007. 17(1): p. 245-251. 18. Emsen, B., et al., The anti-cancer efficacies of diffractaic, lobaric, and usnic acid: In vitro inhibition of glioma. Journal of Cancer Research and Therapeutics, 2018. 14(5): p. 941-951.
18. 19. Yeni, Y., et al., Antitumor Effect of Combination Momordica and Melatonin on Prostate Cancer Pc-3 Cell Line. Acta Physiologica, 2019. 227: p. 71-71.
19. 20. Daneshmandi, S., B. Wegiel, and P. Seth, Blockade of Lactate Dehydrogenase-A (LDH-A) Improves Efficacy of Anti-Programmed Cell Death-1 (PD-1) Therapy in Melanoma. Cancers, 2019. 11(4).
20. 21. Ehrke, M.J., Immunomodulation in cancer therapeutics. International Immunopharmacology, 2003. 3(8): p. 1105-1119.
21. 22. Rodriguez-Garcia, A., et al., Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells. Redox Biology, 2017. 12: p. 634-647.
22. 23. Kanmani, P., et al., Production and purification of a novel exopolysaccharide from lactic acid bacterium Streptococcus phocae PI80 and its functional characteristics activity in vitro. Bioresource Technology, 2011. 102(7): p. 4827-4833.
23. 24. Reiter, R.J., et al., Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis. International Journal of Molecular Sciences, 2017. 18(4).
24. 25. Beckerandre, M., et al., Pineal-Gland Hormone Melatonin Binds and Activates an Orphan of the Nuclear Receptor Superfamily. Journal of Biological Chemistry, 1994. 269(46): p. 28531-28534.
25. 26. Garcia-Navarro, A., et al., Cellular mechanisms involved in the melatonin inhibition of HT-29 human colon cancer cell proliferation in culture. Journal of Pineal Research, 2007. 43(2): p. 195-205.
26. 27. Papazisis, K.T., et al., Effects of melatonin on proliferation of cancer cell lines. Journal of Pineal Research, 1998. 25(4): p. 211-218.
27. 28. Pariente, R., et al., Participation of MT3 melatonin receptors in the synergistic effect of melatonin on cytotoxic and apoptotic actions evoked by chemotherapeutics. Cancer Chemotherapy and Pharmacology, 2017. 80(5): p. 985-998.
28. 29. Farriol, M., et al., In vitro effects of melatonin on cell proliferation in a colon adenocarcinoma line. Journal of Applied Toxicology, 2000. 20(1): p. 21-24.
29. 30. Pitchakarn, P., et al., Momordica charantia leaf extract suppresses rat prostate cancer progression in vitro and in vivo. Cancer Science, 2010. 101(10): p. 2234-2240.
30. 31. Dia, V.P. and H.B. Krishnan, BG-4, a novel anticancer peptide from bitter gourd (Momordica charantia), promotes apoptosis in human colon cancer cells. Scientific Reports, 2016. 6.
31. 32. Popovich, D.G., et al., Momordica charantia Seed Extract Reduces Pre-Adipocyte Viability, Affects Lactate Dehydrogenase Release, and Lipid Accumulation in 3T3-L1 Cells. Journal of Medicinal Food, 2011. 14(3): p. 201-208.
32. 33. Liu, J., et al., Bog Bilberry (Vaccinium uliginosum L.) Extract Reduces Cultured Hep-G2, Caco-2, and 3T3-L1 Cell Viability, Affects Cell Cycle Progression, and Has Variable Effects on Membrane Permeability. Journal of Food Science, 2010. 75(3): p. H103-H107.