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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Human Colon Cancer HT29 Cell Line Treatment with High-Dose LAscorbic Acid Results to Reduced Angiogenic Proteins Expression and Elevated Pro-apoptotic Proteins Expression

Author(s): Kosar Abbasi Samie, Dian Dayer and Zahra Shokati Eshkiki*

Volume 23, Issue 5, 2023

Published on: 13 September, 2022

Page: [470 - 478] Pages: 9

DOI: 10.2174/1566524022666220616141725

Price: $65

Abstract

Background: Some studies have shown anticarcinogenic effects of high dose L-Ascorbic Acid. However, there are controversies around the therapeutic administration of Ascorbic acid as an anticancer medicine.

Objective: We conducted a case-control study to investigate the role of pharmacologic concentration of Ascorbic acid on viability and angiogenesis of the human colon cancer (HT29) cell line.

Methods: The HT29 cells were cultured in DMEM-HG and treated with 10 mM ascorbic acid for 3h. The culture medium was exchanged, and after incubation at 37 ºC for 24 h, the cells were collected and utilized to evaluate viability, ROS production, gene expression and protein expression levels. The control group consisted of untreated HT29 cells. The viability of the cells was determined using the MTT method. Moreover, Nitro Blue Tetrazolium (NBT) was used to detect the ROS production capacity. The mRNA transcript’s level and protein expression were evaluated by Real-time PCR and Western blotting, respectively.

Results: The ascorbic acid-treated group showed a significant increase in ROS production and an obvious reduction in viability compared to the control group. The treated group showed significantly increased levels of both early apoptotic markers (Bax, Cyt C, Caspase3, and Caspase 9) and late apoptotic markers (Caspase 8). Bcl2 expression showed significantly decreased levels relative to the control group. Ascorbic acid therapy substantially reduced the expression of bFGF, bFGFR, PDGF, PDGFR and PLC- γ compared to the control group.

Conclusion: The results confirm that high-dose L-ascorbic acid reduces HT29 cell line viability in vitro.

Keywords: Ascorbic acid, human colon cancer cell line, angiogenesis, apoptosis, ROS, AA

« Previous
[1]
Levine M, Espey MG, Chen Q. Losing and finding a way at C: New promise for pharmacologic ascorbate in cancer treatment. Free Radic Biol Med 2009; 47(1): 27-9.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.04.001] [PMID: 19361554]
[2]
Saha SK, Lee SB, Won J, et al. Correlation between oxidative stress, nutrition, and cancer initiation. Int J Mol Sci 2017; 18(7): 1544.
[http://dx.doi.org/10.3390/ijms18071544] [PMID: 28714931]
[3]
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: How are they linked? Free Radic Biol Med 2010; 49(11): 1603-16.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.09.006] [PMID: 20840865]
[4]
Uetaki M, Tabata S, Nakasuka F, Soga T, Tomita M. Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress. Sci Rep 2015; 5(1): 13896.
[http://dx.doi.org/10.1038/srep13896] [PMID: 26350063]
[5]
Dayer D, Tabandeh MR, Kazemi M. The radio-sensitizing effect of pharmacological concentration of ascorbic acid on human pancreatic cancer cells. Anticancer Agents Med Chem 2020; 20(16): 1927-32.
[http://dx.doi.org/10.2174/1871520620666200612144124] [PMID: 32532196]
[6]
Bober P, Alexovic M, Talian I, et al. Proteomic analysis of the vitamin C effect on the doxorubicin cytotoxicity in the MCF-7 breast cancer cell line. J Cancer Res Clin Oncol 2017; 143(1): 35-42.
[http://dx.doi.org/10.1007/s00432-016-2259-4] [PMID: 27620743]
[7]
Huijskens MJ, Walczak M, Sarkar S, et al. Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy. Cytotherapy 2015; 17(5): 613-20.
[http://dx.doi.org/10.1016/j.jcyt.2015.01.004] [PMID: 25747742]
[8]
Vissers MCM, Das AB. Potential mechanisms of action for vitamin C in cancer: Reviewing the evidence. Front Physiol 2018; 9: 809.
[http://dx.doi.org/10.3389/fphys.2018.00809] [PMID: 30018566]
[9]
Telang S, Clem AL, Eaton JW, Chesney J. Depletion of ascorbic acid restricts angiogenesis and retards tumor growth in a mouse model. Neoplasia 2007; 9(1): 47-56.
[http://dx.doi.org/10.1593/neo.06664] [PMID: 17325743]
[10]
Mikirova NA, Ichim TE, Riordan NH. Anti-angiogenic effect of high doses of ascorbic acid. J Transl Med 2008; 6(1): 50.
[http://dx.doi.org/10.1186/1479-5876-6-50] [PMID: 18789157]
[11]
Wenzel U, Nickel A, Kuntz S, Daniel H. Ascorbic acid suppresses drug-induced apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions. Carcinogenesis 2004; 25(5): 703-12.
[http://dx.doi.org/10.1093/carcin/bgh079] [PMID: 14754875]
[12]
Monti DA, Mitchell E, Bazzan AJ, et al. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One 2012; 7(1): e29794.
[http://dx.doi.org/10.1371/journal.pone.0029794] [PMID: 22272248]
[13]
Lin SR, Chang CH, Hsu CF, et al. Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence. Br J Pharmacol 2020; 177(6): 1409-23.
[http://dx.doi.org/10.1111/bph.14816] [PMID: 31368509]
[14]
Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: A brief review. Adv Pharm Bull 2017; 7(3): 339-48.
[http://dx.doi.org/10.15171/apb.2017.041] [PMID: 29071215]
[15]
Zasowska-Nowak A, Nowak PJ. Ciałkowska-Rysz A. High-dose vitamin C in advanced-stage cancer patients. Nutrients 2021; 13(3): 735.
[http://dx.doi.org/10.3390/nu13030735] [PMID: 33652579]
[16]
Satheesh NJ, Samuel SM, Büsselberg D. Combination therapy with vitamin C could eradicate cancer stem cells. Biomolecules 2020; 10(1): 79.
[http://dx.doi.org/10.3390/biom10010079] [PMID: 31947879]
[17]
Kazmierczak-Barańska J, Boguszewska K, Adamus-Grabicka A, Karwowski BT. Two faces of vitamin C antioxidative and pro oxidative agent nutrients. 2020; 12(5): 1501.
[18]
Chen Q, Espey MG, Sun AY, et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci USA 2008; 105(32): 11105-9.
[http://dx.doi.org/10.1073/pnas.0804226105] [PMID: 18678913]
[19]
Pawlowska E, Szczepanska J, Blasiak J. Pro-and antioxidant effects of vitamin C in cancer in correspondence to its dietary and pharmacological concentrations. Oxid Med Cell Longev 2019.
[http://dx.doi.org/10.1155/2019/7286737]
[20]
Vuyyuri SB, Rinkinen J, Worden E, Shim H, Lee S, Davis KR. Ascorbic acid and a cytostatic inhibitor of glycolysis synergistically induce apoptosis in non-small cell lung cancer cells. PLoS One 2013; 8(6): e67081.
[http://dx.doi.org/10.1371/journal.pone.0067081] [PMID: 23776707]
[21]
Pathi SS, Lei P, Sreevalsan S, Chadalapaka G, Jutooru I, Safe S. Pharmacologic doses of ascorbic acid repress Specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells. Nutr Cancer 2011; 63(7): 1133-42.
[http://dx.doi.org/10.1080/01635581.2011.605984] [PMID: 21919647]
[22]
Attia M, Essa EA, Zaki RM, Elkordy AA. An overview of the antioxidant effects of ascorbic acid and alpha lipoic acid (in liposomal forms) as adjuvant in cancer treatment. Antioxidants 2020; 9(5): 359.
[http://dx.doi.org/10.3390/antiox9050359] [PMID: 32344912]
[23]
Lugano R, Ramachandran M, Dimberg A. Tumor angiogenesis: Causes, consequences, challenges and opportunities. Cell Mol Life Sci 2020; 77(9): 1745-70.
[http://dx.doi.org/10.1007/s00018-019-03351-7] [PMID: 31690961]
[24]
Farnsworth RH, Lackmann M, Achen MG, Stacker SA. Vascular remodeling in cancer. Oncogene 2014; 33(27): 3496-505.
[http://dx.doi.org/10.1038/onc.2013.304] [PMID: 23912450]
[25]
Roomi MW, Roomi N, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. Inhibitory effect of a mixture containing ascorbic acid, lysine, proline and green tea extract on critical parameters in angiogenesis. Oncol Rep 2005; 14(4): 807-15.
[http://dx.doi.org/10.3892/or.14.4.807] [PMID: 16142336]
[26]
Wagner SC, Markosian B, Ajili N, et al. Intravenous ascorbic acid as an adjuvant to interleukin-2 immunotherapy. J Transl Med 2014; 12(1): 127.
[http://dx.doi.org/10.1186/1479-5876-12-127] [PMID: 24884532]
[27]
Parsons KK, Maeda N, Yamauchi M, Banes AJ, Koller BH. Ascorbic acid-independent synthesis of collagen in mice. Am J Physiol Endocrinol Metab 2006; 290(6): E1131-9.
[http://dx.doi.org/10.1152/ajpendo.00339.2005] [PMID: 16352673]
[28]
Shibuya M. Vascular Endothelial Growth Factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: A crucial target for anti-and pro-angiogenic therapies. Genes Cancer 2011; 2(12): 1097-105.
[http://dx.doi.org/10.1177/1947601911423031] [PMID: 22866201]
[29]
Zachary I, Gliki G. Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc Res 2001; 49(3): 568-81.
[http://dx.doi.org/10.1016/S0008-6363(00)00268-6] [PMID: 11166270]
[30]
Yeom CH, Lee G, Park JH, et al. High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis. J Transl Med 2009; 7(1): 70.
[http://dx.doi.org/10.1186/1479-5876-7-70] [PMID: 19671184]
[31]
Tran TA, Kinch L, Peña-Llopis S, et al. Platelet-derived growth factor/vascular endothelial growth factor receptor inactivation by sunitinib results in Tsc1/Tsc2-dependent inhibition of TORC1. Mol Cell Biol 2013; 33(19): 3762-79.
[http://dx.doi.org/10.1128/MCB.01570-12] [PMID: 23878397]
[32]
Verrax J, Calderon PB. The controversial place of vitamin C in cancer treatment. Biochem Pharmacol 2008; 76(12): 1644-52.
[http://dx.doi.org/10.1016/j.bcp.2008.09.024]
[33]
Halabi IE, Bejjany R, Nasr R, Mukherji D, Temraz S, Nassar FJ. Ascorbic acid in colon cancer: From the basic to the clinical applications. Int J Mol Sci 2018; 19(9): 2752.
[34]
Jain A, Tiwari A, Verma A, Jain SK. Vitamins for cancer prevention and treatment: An insight. Curr Mol Med 2017; 17(5): 321-40.
[PMID: 29210648]
[35]
van Gorkom GNY, Lookermans EL, Van Elssen CHMJ, Bos GMJ. The effect of vitamin C (ascorbic acid) in the treatment of patients with cancer: A systematic review. Nutrients 2019; 11(5): 977.
[http://dx.doi.org/10.3390/nu11050977] [PMID: 31035414]

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