A Comparison of Curcumin and Nanocurcumin Effect on the expression of the vascular endothelial growth factor (VEGF-A) in HeLa cell line

Vahedian Sadeghi, Rezvaneh; Parsania, Masoud; Sadeghizadeh, Majid; Haghighat, Setareh; Mortazavi Farsani, Seyedeh Sahar

A Comparison of Curcumin and Nanocurcumin Effect on the expression of the vascular endothelial growth factor (VEGF-A) in HeLa cell line

Document Type : Original Research

Authors

Rezvaneh Vahedian Sadeghi ¹

masoud Parsania ²

Majid Sadeghizadeh ³

Setareh Haghighat ⁴

Seyedeh Sahar Mortazavi Farsani ⁵

¹ Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University,Tehran, Iran

² Department of Microbiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad university, Tehran, Iran.

³ Genetics Department, BiologicalSciences Faculty, Tarbiat ModaresUniversity, Tehran, Iran

⁴ Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University,Tehran,Iran.

⁵ Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

Abstract

Abstract

Introduction: Cervical cancer is the fourth most common cancer among women. In recent years, attention has increased to natural products such as curcumin with anti-cancer potential as a therapeutic supplement. However, due to its poor solubility, its clinical use is limited. In this regard, in this study, to improve clinical parameters, the effects of nanocurcumin on the angiogenesis inhibition of cervical cancer were investigated and compared with free curcumin.

Materials and Methods: MTT method was used to evaluate the proliferation of the HeLa cell line with free curcumin and nanocurcumin at different doses and time intervals and the rate of apoptosis was assessed by flow cytometry. Then, the expression of the vascular endothelial growth factor (VEGF-A) gene in HeLa cells was measured by Real-Time PCR and Western blotting, respectively.

Results: According to IC50 for 48 hours in the HeLa cell line, which was 15 μM/ml and 50 μM/ml for nanocurcumin and free curcumin, respectively, the nanocurcumin showed a greater lethal effect. VEGF-A gene expression (p <0.0001) and protein level (p <0.01) were significantly lower following nano-curcumin treatment than free curcumin.

Conclusion: Nanocarrier increased the solubility and further inhibited the proliferation of cervical cancer HeLa cells and was three times more effective than curcumin in inhibiting angiogenesis at the same concentration. Therefore, nanocurcumin can be a good option for drug supplementation along with routine cervical cancer treatment.

Keywords: Cervical cancer, Nanocurcumin, HeLa cell, VEGF-A.

Keywords

Cervical cancer

Nano-Curcumin

HeLa cell

VEGF-A

20.1001.1.23222115.1400.13.1.7.6

Subjects

Pharmaceutical Biotechnology

1. Zur Hausen, H., Papillomaviruses and cancer: from basic studies to clinical application. Nature reviews cancer, 2002. 2(5): p. 342-350.
2. Bosch, F.X., et al., The causal relation between human papillomavirus and cervical cancer. Journal of clinical pathology, 2002. 55(4): p. 244-265.
3. Creuzet, S., et al., Negative effect of Hox gene expression on the development of the neural crest-derived facial skeleton. 2002.
4. Mackenzie, F. and C. Ruhrberg, Diverse roles for VEGF-A in the nervous system. Development, 2012. 139(8): p. 1371-1380.
5. Guidi, A.J., et al., Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia. JNCI: Journal of the National Cancer Institute, 1995. 87(16): p. 1237-1245.
6. Lee, I.-J., et al., Prognostic value of vascular endothelial growth factor in Stage IB carcinoma of the uterine cervix. International Journal of Radiation Oncology* Biology* Physics, 2002. 54(3): p. 768-779.
7. Toussaint-Smith, E., D.B. Donner, and A. Roman, Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors. Oncogene, 2004. 23(17): p. 2988-2995.
8. Chen, W., et al., Human papillomavirus causes an angiogenic switch in keratinocytes which is sufficient to alter endothelial cell behavior. Virology, 2007. 367(1): p. 168-174.
9. Rahman, I., S.K. Biswas, and P.A. Kirkham, Regulation of inflammation and redox signaling by dietary polyphenols. Biochemical pharmacology, 2006. 72(11): p. 1439-1452.
10. Tirkey, N., et al., Curcumin, a diferuloylmethane, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rat kidneys. BMC pharmacology, 2005. 5(1): p. 1-10.
11. Deeb, D., et al., Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis. Journal of experimental therapeutics & oncology, 2005. 5(2).
12. Tønnesen, H.H. and J. Karlsen, Studies on curcumin and curcuminoids. Zeitschrift für Lebensmittel-Untersuchung und Forschung, 1985. 180(5): p. 402-404.
13. Wang, T.-y. and J.-x. Chen, Effects of curcumin on vessel formation insight into the pro-and antiangiogenesis of curcumin. Evidence-Based Complementary and Alternative Medicine, 2019. 2019.
14. Anand, P., et al., Bioavailability of curcumin: problems and promises. Molecular pharmaceutics, 2007. 4(6): p. 807-818.
15. Shehzad, A., F. Wahid, and Y.S. Lee, Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Archiv der Pharmazie, 2010. 343(9): p. 489-499.
16. Shehzad, A., et al., Curcumin therapeutic promises and bioavailability in colorectal cancer. Drugs of today, 2010. 46(7): p. 523.
17. Shaikh, J., et al., Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. European journal of pharmaceutical sciences, 2009. 37(3-4): p. 223-230.
18. Bisht, S., et al., Polymeric nanoparticle-encapsulated curcumin (" nanocurcumin"): a novel strategy for human cancer therapy. Journal of nanobiotechnology, 2007. 5(1): p. 1-18.
19. Farsani, S.S.M., et al., Nanocurcumin as a novel stimulator of megakaryopoiesis that ameliorates chemotherapy-induced thrombocytopenia in mice. Life Sciences, 2020. 256: p. 117840.
20. TAHMASEBI, B.M., et al., Dendrosomal Nano-curcumin, the Novel Formulation to Improve the Anticancer Properties of Curcumin. 2015.
21. Masters, J.R., HeLa cells 50 years on: the good, the bad and the ugly. Nature Reviews Cancer, 2002. 2(4): p. 315-319.
22. El-Azab, M., et al., Anti-angiogenic effect of resveratrol or curcumin in Ehrlich ascites carcinoma-bearing mice. European journal of pharmacology, 2011. 652(1-3): p. 7-14.
23. Carvalho Ferreira, L., et al., Effect of curcumin on pro-angiogenic factors in the xenograft model of breast cancer. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 2015. 15(10): p. 1285-1296.
24. Pradhan, N., et al., Curcumin nanoparticles inhibit corneal neovascularization. Journal of Molecular Medicine, 2015. 93(10): p. 1095-1106.
25. Li, L., et al., Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer. Molecular cancer therapeutics, 2007. 6(4): p. 1276-1282.
26. Alizadeh, A.M., et al., Chemoprevention of azoxymethane-initiated colon cancer in rat by using a novel polymeric nanocarrier–curcumin. European journal of pharmacology, 2012. 689(1-3): p. 226-232.
27. Montazeri, M., et al., Dendrosomal curcumin nanoformulation modulate apoptosis-related genes and protein expression in hepatocarcinoma cell lines. International journal of pharmaceutics, 2016. 509(1-2): p. 244-254.
28. Babaei, E., et al., Dendrosomal curcumin significantly suppresses cancer cell proliferation in vitro and in vivo. International immunopharmacology, 2012. 12(1): p. 226-234.
29. Sadeghzadeh, H., et al., The effects of nanoencapsulated curcumin-Fe3O4 on proliferation and hTERT gene expression in lung cancer cells. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 2017. 17(10): p. 1363-1373.
30. Zaman, M.S., et al., Curcumin nanoformulation for cervical cancer treatment. Scientific reports, 2016. 6(1): p. 1-14.
31. Syng-Ai, C., A.L. Kumari, and A. Khar, Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2. Molecular cancer therapeutics, 2004. 3(9): p. 1101-1108.
32. Flowers, L.C., et al., Curcumin suppresses growth of cervical cancer cells. 2005, AACR.
33. Ravindran, J., S. Prasad, and B.B. Aggarwal, Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? The AAPS journal, 2009. 11(3): p. 495-510.