Monday 4 September 2017

Anticancer Potential of EDTA: A Preliminary in Vitro Study




To determine the potential anticancer activity of ethylenediaminetetraacetic acid (EDTA), six cancer cell lines of human origin (U937, C-32, HeLa, HSC-2, Molt-4, and U87-MG) were treated with different concentrations of EDTA, and then assayed for cell viability. The melanoma C-32 cell line, which was found to be moderately sensitive to EDTA, was then compared to normal melanocytes, on the other hand, a relatively resistant cell line Molt-4 was then chosen for further investigation to determine the role of calcium-chelating activity of EDTA against the cells. The result showed that the cell lines had different levels of sensitivity to EDTA; and, that melanoma cells are more sensitive compared to melanocytes. Comparison of EDTA toxicity to that of a known calcium-selective chelator, BAPTA, also showed marked differences in toxicity profiles, which may suggest that the calcium chelating ability of EDTA may not be a major player in its toxicity against the cancer cells. Further study should be done to investigate how such anticancer effects work in vivo; and also, if EDTA can be utilized as an enhancer of other anticancer therapies, such as chemotherapy, radiotherapy and hyperthermia.

Ethylenediaminetetraacetic acid (EDTA) is a known metal chelating agent that is clinically being used to treat heavy metal poisoning, such as mercury or lead poisoning; and also, to remove excess iron in blood. In the body, EDTA is eliminated in the kidneys, which is clinically being utilized to determine the glomerular filtration rate in children. With EDTA’s iron chelation ability, it is being proposed that EDTA could be used as an additive in an agent that protects skin from radiation such as antiphotoaging products. EDTA has also been shown as a potent inhibitor of matrix metalloproteinases and an important component in the design of drug. carrying liposomes. While a study also found that EDTA could be a useful and well-tolerated adjuvant for enhancing intratumoral effects of cisplatin chemotherapy, other studies found it to affect subcellular expression of clusterin protein in human colon adenocarcinoma COLO 205 cell line. EDTA may also inhibit the effect of bleomycin and was shown to prevent bleomycin nucleasic activity, a process important for bleomycin’s ability to induce cancer cell apoptosis. EDTA may also prevent iron from the iron-doxorubicin complex that produces damaging reactive oxygen species. In these studies where EDTA counters the effects of anticancer drugs, it may serve as an adjunctive therapy in preventing unwanted effects in the event of accidental extravasation injury during the administration of anticancer drugs. This in vitro preliminary study aims to investigate the potential of EDTA as an anticancer agent or as a potential enhancer of anticancer therapy.

Six cancer cell lines, all of human origin, were used in the study. The human cell line used were the: myelolymphocytic (U937), melanoma (C-32), epithelial adenocarcinoma (HeLa), squamous (HSC-2), T lymphoblastic leukemia (Molt-4), and glioblastoma (U87-MG) cell lines. The cells were cultured in ISSN: 2474-6797 ABSTRACT To determine the potential anticancer activity of ethylenediaminetetraacetic acid (EDTA), six cancer cell lines of human origin (U937, C-32, HeLa, HSC-2, Molt-4, and U87-MG) were treated with different concentrations of EDTA, and then assayed for cell viability. The melanoma C-32 cell line, which was found to be moderately sensitive to EDTA, was then compared to normal melanocytes, on the other hand, a relatively resistant cell line Molt-4 was then chosen for further investigation to determine the role of calcium-chelating activity of EDTA against the cells. The result showed that the cell lines had different levels of sensitivity to EDTA; and, that melanoma cells are more sensitive compared to melanocytes. Comparison of EDTA toxicity to that of a known calcium-selective chelator, BAPTA, also showed marked differences in toxicity profiles, which may suggest that the calcium chelating ability of EDTA may not be a major player in its toxicity against the cancer cells. Further study should be done to investigate how such anticancer effects work in vivo; and also, if EDTA can be utilized as an enhancer of other anticancer therapies, such as chemotherapy, radiotherapy and hyperthermia. www.mathewsopenaccess.com Citation: Feril LB Jr, Ogawa K, Watanabe A, Ogawa R, et al. (2017). Anticancer Potential of EDTA: A Preliminary in Vitro Study. M J Canc. 2 2(1): 009. minimum essential medium (MEM) with Earle’s salts and Lglutamine supplemented with 1% essential amino acids and 10% fetal bovine serum (Gibco, Invitrogen Corporation, Groningen, The Netherlands) under humidified air and 5% CO2

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