Effect of Vitamin B Complex on Colon Cancer by Photodynamic Therapy

Abstract

Objective: Colon cancer is a chronic fatal disease that severely affects the quality of life of patients and is associated with various complications. Vitamin B complex shows positive anti-inflammatory effects when taken as a food supplement. The aim of this study was to investigate the anti-cancer effect of vitamin B complex with liposomes in colon cancers (HCT-116 and HT-29 cell lines) using photodynamic therapy. Material-Method: Vitamin B complex, which is the first step of the study, was encapsulated with liposome. Vitamin B complex with liposome was characterized by Zetasizer device. The MTT (3-4,5-dimethyl-thiazolyl-2,5-diphenyltetrazolium bromide) assay was used to determine the % survival rates in HCT-116 and HT-29 cell lines. The same cell lines were also analyzed by flow cytometry to show which death pathways were selected by the vitamin B complex with the effect of photodynamic therapy. Results: It was found that the dimensions of the vitamin B complex with liposomes varied between 100 nm and 200 nm. Liposomal vitamin B complex (photosensitizer) at 7.5 J/cm2 light dose at 0.25 mg/mL in the dark experiment, while the percentage of HCT-116 cell viability was 75%, this rate decreased to 47% after the light experiment (****p <0.001). While the percentage of HT-29 cell viability was 70% in the dark test for 0.5 mg/mL vitamin B complex solution, this rate decreased to 35% after the light test (****p<0.001). The desired photodynamic efficiency is closer to these results. In the cell death pathway assay, the concentration of liposomal vitamin B complex was applied to HCT-116 and HT-29 cells at 1 mg/mL. While 40% apoptosis was observed in the HCT-116 cell line, 60% apoptosis was observed in the HT-29 cell line. Conclusion: Repositioning of marketed drugs has emerged as a new approach to the discovery of new anti-tumor drugs. The development of new uses for marketed drugs has proven to be an efficient and rapid way to develop new anti-tumor drugs. Our data suggest that the in vitro use of vitamin B complex with photodynamic therapy is promising in some types of colorectal cancer.

Keywords

• Photodynamic therapy
• colon cancer
• drug repositioning
• vitamin B complex
• laser

Vitamin B Kompleksinin Fotodinamik Terapiyle Kolon Kanserine Etkisi

Abstract

Amaç: Kolon kanserleri, hastanın yaşam kalitesini derinden etkileyen ve çeşitli komplikasyonlarla ilişkili kronik ölümcül bir hastalıktır. Vitamin B kompleksi, gıda takviyesi olarak alındığında olumlu anti-inflamatuar etkiler göstermektedir. Bu çalışma, fotodinamik terapiyle lipozomlu vitamin B kompleksinin kolon kanserlerinde (HCT-116 ve HT-29 hücre hattı) anti-kanser etkisini araştırmayı amaçlamıştır. Materyal- Metot: Çalışmanın birinci basamağını oluşturan Vitamin B kompleksi lipozom ile kapsüle edildi. Lipozomlu vitamin B kompleksi Zetasizer cihazı ile karakterize edildi. Lipozomlu vitamin B kompleksi MTT (3-4,5-dimetil-tiyazolil-2,5-difeniltetrazolyum bromür) testi ile HCT-116 ve HT-29 hücre hattında % canlılık oranlarına bakılmıştır. Aynı hücre hatlarında vitamin B kompleksinin fotodinamik terapi etkisiyle hangi ölüm yolaklarını seçtiğini göstermek için de akış sitometrisi kullanılarak analiz edilmiştir. Bulgular: Lipozomlu vitamin B kompleksinin boyutları 100 nm ile 200 nm aralığında değiştiği belirlendi. Lipozomlu vitamin B kompleksi (fotosensitizer) 7,5 J/cm2 ışık dozunda 0,25 mg/ mL'de karanlık deneyinde HCT-116 hücre canlılık yüzdesi %75 iken ışık deneyi sonrası bu oran %47’lere düşmüştür (****p<0.001). 0,5 mg/mL vitamin B kompleksi çözeltisi için yapılan karanlık deneyinde HT-29 hücre canlılık yüzdesi %70 iken ışık deneyi sonrası bu oran %35’lere düşmüştür (****p<0.001). Arzu edilen fotodinamik etkinlik bu sonuçlara daha yakındır. Hücre ölüm yolakları belirleme deneyinde lipozomlanmış vitamin B kompleksinin konsantrasyonu 1mg/mL olarak HCT-116 ve HT-29 hücrelerine uygulanmıştır. HCT-116 hücre hattında %40 oranında apoptoz görülürken HT-29 hücre hattında %60 oranında apoptoz görüldü. Sonuç: Pazarlanan ilaçları yeniden konumlandırmak, yeni antitümör ilaçları keşfetmek için yeni bir yaklaşım olarak ortaya çıkmıştır. Pazarlanan ilaçlar için yeni kullanım alanlarının geliştirilmesi, yeni anti-tümör ilaçları geliştirmenin etkili ve hızlı yolu olduğu kanıtlanmıştır. Verilerimiz in-vitro olarak bazı kolon kanser türlerinde vitamin B kompleksinin fotodinamik terapiyle kullanımının ümit vaat ettiğini savunmaktadır.

Keywords

• Fotodinamik terapi
• kolon kanseri
• ilaç yeniden konumlandırma
• vitamin B kompleksi
• lazer

References

1. Siegel, R.L., Miller, K.D., and Jemal, A. 2017. Cancer statistics 2017. CA Cancer J. Clin. 67 (1), 7–30.
2. Yoonjeong, C., Erez, T., Reynolds, I. J., Kumar, D., Jermaine, R., Gregory, K., et al. (2018). Drug repurposing from the perspective of pharmaceutical companies. Br. J. Pharmacol. 175 (2), 168–180.
3. Reddy, A.S., and Zhang, S. 2013. Polypharmacology: drug discovery for the future. Expert Rev. Clin. Pharmacol. 6 (1), 41–47.
4. Lopez-Lazaro, M. What is the main cause of cancer? J. Cancer Stud. Ther. 2016, 1, 1–2.
5. Rebecca, L.S.; Kimberly, D.M.; Ahmedin, J. Cancer statistics. CA Cancer J. Clin. 2019, 69, 7–34.
6. Deng, X., Shao, Z., Zhao, Y. Solutions to the drawbacks of photothermal and photodynamic cancer therapy. Adv Sci. 2021;8(3):2002504.
7. Suzuki, T., Tanaka, M., Sasaki, M., Ichikawa, H., Nishie, H., Kataoka, H. Vascularshutdown by photodynamic therapy using talaporfn sodium. Cancers.2020.
8. Russell-Jones, G., McTavish, K., McEwan, J., Rice, J., Nowotnik, D. Vitamin-mediated targeting as a potential mechanism to increase drug uptake by tumours. J. Inorg. Biochem. 2004, 98, 1625–1633.

9. Vadlapudi, A.D., Krishna, R., Pal, D., Mitra, A.K. Molecular expression and functional activity of sodium dependent multivitamin transporter in human prostate cancer cells. Int. J. Pharm. 2012, 436, 324–331.
10. Patel, M., Vadlapatla, R.K., Shah, S., Mitra, A.K. Biotin uptake by T47D breast cancer cells: Functional and molecular evidence of sodium-dependent multivitamin transporter (SMVT). Int. J. Pharm. 2013, 441, 535–543.
11. Juzeniene, A. Chlorin e6-based photosensitizers for photodynamic therapy and photodiagnosis. Photodiagnosis Photodyn. Ther. 2009, 6, 26630–26637.
12. Kamkaew, A., Cheng, L., Goel, S., Valdovinos, V.F., Barnhart, T.E., Liu, Z., Cai, W.B. Cerenkov radiationinduced photodynamic therapy using chlorin e6-loadedhollow mesoporous silica nanoparticles. ACS Appl.Mater. Interfaces 2016, 8, 26630–26637.
13. Peloi, L.S., Soares, R.R.S., Biondo, C.E.G. , Souza, V.R., Hioka, N., Kimura, E.2008. Photodynamic effect of light-emitting diode light on cell growth inhibition induced by methylene blue, Journal of Biosciences.,33(2), 231–237.
14. Kwiatkowski, S., Knap, B., Przystupski, D., Saczko, J., Kedzierska, E., Knap-czop, K., Kotlinska, J., Michel, O., Kotowski, K., Kulbacka, J. Photodunamic therapy–mechanisms, photosensitizers and combinations.Biomed. Pharm. 2018, 106, 1098–1107.
15. Pramuala, S., Lirdprapamongkol, K., Svasti, J., Bergkvist, M., Jouan-Hureaux, V., Arnoux, P., Frochot, C., Barberi-Heyob, M., Niamsiria, N. Polymer-lipid-PEG hybrid nanoparticles as photosensitizer carrier for photodynamic therapy. J. Photochem. Photobiol. B Biol. 2017, 173, 12–22.
16. Ghosh, S., Carter, K.A., Lovell, J.F. Liposomal formulations of photosensitizers. Biomaterials 2019, 218, 119341.
17. Muddineti, O.S., Rompicharla, S.V.K., Kumari, P., Bhatt, H., Ghosh, B., Biswas, S. Lipid and poly (ethylene glycol)-conjugated bi-functionalized chlorine e6 micelles for NIR-light induced photodynamic therapy. Photodiagnosis Photodyn. Ther. 2020, 29, 101633.
18. Marangon, I., Ménard-Moyon, C., Silva, A.K.A., Bianco, A., Luciani, N., Gazeau, F. Synergic mechanisms of photothermal and photodynamic therapies mediated by photosensitizer/carbon nanotube complexes. Carbon 2016, 97, 110–123.
19. Mantareva, V., Iliev, I., Sulikovska, I., Durmuş, M., Angelov, I. Cobalamin (Vitamin B12) in Anticancer Photodynamic Therapy with Zn(II) Phthalocyanines. Int. J. Mol. Sci. 2023; 24(5):4400.
20. Yurttaş, G.A., Çınar K. P. Aeruginosa Bakterisinin Vitamin B Kompleksi ve Kırmızı Lazer Kullanılarak İnaktive Edilmesi. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi. 2022; 13(3): 353-363.
21. Su, L., Huang, J., Li, H. Chitosan-riboflavin composite film based on photodynamic inactivation technology for antibacterial food packaging. Int. J. Biol. Macromol. 2021;172:231-240.
22. Yurttaş, G.A., Gökduman, K., Hekim, S.N. 2022. Liposomes Loaded with Activatable Disulfide Bridged Photosensitizer: Towards Targeted and Effective Photodynamic Therapy on Breast Cancer Cells. Biointerface Res. Appl. Chem., Volume 12, Issue 1, 304 -325.
23. Birgül, K., Uba, A.İ., Çuhadar, O., Koçyiğit, S.S., Tiryaki, S., Tiber, P.M., Orun,O., Telci, D., Yılmaz, Ö., Kemal Yelekçi, K., Küçükgüzel, G.K. ‘’Synthesis and molecular modeling of MetAP2 of thiosemicarbazides, 1,2,4-triazoles, thioethers derived from (S)-Naproxen as possible breast cancer agents’’. J. Mol. Struct. 1259 (2022) 132739.
24. Pham, T., Bui, L., Kim, G., Hoang, D., Tran, T., Hoang, M. Cancers in Vietnam Burden and Control Efforts: A Narrative Scoping Review. Cancer Contr. 2019, 26, 1–14.
25. Naidoo, C., Kruger, C.A., Abrahamse, H. Photodynamic Therapy for Metastatic Melanoma Treatment. Technol. Cancer Res. Treat. 2018, 17, 1–15.
26. Chen, D., Song, M., Huang, J., Chen, N., Xue, J., Huang, M. Photocyanine: A novel and effective phthalocyanine-based photosensitizer for cancer treatment. J. Innov. Opt. Health Sci. 2020, 13, 2030009.
27. O’driscoll, L.; Clynes, M. Biomarkers and multiple drug resistance in breast cancer. Curr. Cancer Drug Targets 2006, 6, 365–384.
28. Jackowska, A., Gryko, D. Vitamin B12 Derivatives Suitably Tailored for the Synthesis of Photolabile Conjugates. Org. Lett. 2021, 23, 4940–4944.
29. Abrahamse, H., Tynga, I. Nano-mediated photodynamic therapy for cancer: Enhancement of cancer specificity and therapeutic effects. Nanomaterials 2018, 923, 1–14.
30. Choi, Y., Weissleder, R., Tung, C.H. Selective Antitumor Effect of Novel Protease-Mediated Photodynamic Agent. Cancer Res. 2006; 66(14), 7225-7229.
31. Gibis, M., Vogt, E., Weiss J. Encapsulation of polyphenolic grape seed extract in polymercoated liposomes. Food & Funct. 2012; 3(3),246-254.
32. Oskouei, Z.M, Biçim, G., Yalçın, A.S. C vitamini, E vitamini ve polifenol ekstresi içeren lipozomların eldesi ve antioksidan aktivitelerinin karşılaştırılması. Marmara Med J. 2014; 27, 166-170.
33. Kırtıl, E., Öztop, M.H. Liposomes as an Encapsulation Agent for Food Applications: Structure, Characterization, Manufacture and Stability. Akademik Gıda. 2014; 12(4) ,41-57.
34. Slow-targeted release of a ruthenium anticancer agent from vitamin B 12 functionalized marine diatom microalgae. 2020. Accessed February 25, 2023.
35. Chun, J.Y., Choi, M.J., Min, S.G., Weiss, J. Formation and stability of multiple-layered liposomes by layer-by-layer electrostatic deposition of biopolymers. Food Hydrocoll. 2013; 30(1), 249-257.
36. José, H. Correia, J.H., Rodrigues, J.A., Pimenta, S., Dong, T., Yang, Z., Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions. Pharmaceutics 2021, 13(9), 1332.
37. De Jode, M.L., Mcgıllıgan, J.A., Dılkes, M.G., Cameron, I., Hart, P.B., Grahn, M.F. A Comparison of Novel Light Sources for Photodynamic Therapy. Lasers in Medical Science. 1997, 12:260-268.
38. Yurttaş¸ A.G., Sevim, A.M., Çınar, K., Atmaca, G.Y., Erdoğmus, A., Gül, A. The effects of zinc(II)phthalocyanine photosensitizers on biological activities of epitheloid cervix carcinoma cells and precise determination of absorbed fluence at a specific wavelength. Dyes Pigm.. 2022; 198, 110012 .