L-Ascorbic Acid and α-Tocopherol Synergistically Triggers Apoptosis Inducing Antileukemic Effects of Arsenic Trioxide via Oxidative Stress in Human Acute Promyelocytic Leukemia Cells
Chemosensitization is an effective strategy to overcome the drawbacks of arsenic trioxide (As2O3) treatment, which may be possible through the use of dietary supplements in combination. The present investigation evaluates the synergistic mechanism of action of vitamins, such as L-ascorbic acid (L-AA...
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00065/full |
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| author | Radhakrishnan Chandraprabha Vineetha Radhakrishnan Chandraprabha Vineetha Sreedharan Hariharan Abdul Jaleel Mahesh Chandran Raveendran Harikumaran Nair |
| author_facet | Radhakrishnan Chandraprabha Vineetha Radhakrishnan Chandraprabha Vineetha Sreedharan Hariharan Abdul Jaleel Mahesh Chandran Raveendran Harikumaran Nair |
| author_sort | Radhakrishnan Chandraprabha Vineetha |
| collection | DOAJ |
| description | Chemosensitization is an effective strategy to overcome the drawbacks of arsenic trioxide (As2O3) treatment, which may be possible through the use of dietary supplements in combination. The present investigation evaluates the synergistic mechanism of action of vitamins, such as L-ascorbic acid (L-AA) and α-tocopherol (α-TOC) in As2O3 chemotherapy using human leukemia (HL-60) cells. In vitro assays on the cytotoxicity of As2O3 and vitamins and cellular apoptotic evidences were done; a proteomic investigation with mass spectrometry was also performed. The combination of L-AA and α-TOC potentiates As2O3 cytotoxicity in HL-60 cells, substantiated by depletion in antioxidant status, mitochondrial transmembrane potential, and inhibition of nuclear factor erythroid 2-related factor 2 and B-cell lymphoma 2 transcription factors. Mass spectrometry results showed decreased expression of proteins regulating cell cycle and translation in cells treated with As2O3, L-AA, and α-TOC when compared with As2O3-treated sample. In addition, this combination treatment identified numerous proteins associated with apoptosis and cell stress. HL-60 cells became more prone to As2O3 on exposure to L-AA and α-TOC, indicating that this combination may be a promising approach to increase the outcome of As2O3 chemotherapy. |
| first_indexed | 2024-04-13T03:12:47Z |
| format | Article |
| id | doaj.art-1ad67713cd43478696ce83a82ee0a514 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T03:12:47Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-1ad67713cd43478696ce83a82ee0a5142022-12-22T03:05:00ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-02-011010.3389/fonc.2020.00065494392L-Ascorbic Acid and α-Tocopherol Synergistically Triggers Apoptosis Inducing Antileukemic Effects of Arsenic Trioxide via Oxidative Stress in Human Acute Promyelocytic Leukemia CellsRadhakrishnan Chandraprabha Vineetha0Radhakrishnan Chandraprabha Vineetha1Sreedharan Hariharan2Abdul Jaleel3Mahesh Chandran4Raveendran Harikumaran Nair5Physiology Research Laboratory, School of Biosciences, Mahatma Gandhi University, Kottayam, IndiaLaboratory of Cytogenetics and Molecular Diagnostics, Division of Cancer Research, Regional Cancer Centre, Trivandrum, IndiaLaboratory of Cytogenetics and Molecular Diagnostics, Division of Cancer Research, Regional Cancer Centre, Trivandrum, IndiaProteomics Facility, Rajiv Gandhi Centre for Biotechnology, Trivandrum, IndiaProteomics Facility, Rajiv Gandhi Centre for Biotechnology, Trivandrum, IndiaPhysiology Research Laboratory, School of Biosciences, Mahatma Gandhi University, Kottayam, IndiaChemosensitization is an effective strategy to overcome the drawbacks of arsenic trioxide (As2O3) treatment, which may be possible through the use of dietary supplements in combination. The present investigation evaluates the synergistic mechanism of action of vitamins, such as L-ascorbic acid (L-AA) and α-tocopherol (α-TOC) in As2O3 chemotherapy using human leukemia (HL-60) cells. In vitro assays on the cytotoxicity of As2O3 and vitamins and cellular apoptotic evidences were done; a proteomic investigation with mass spectrometry was also performed. The combination of L-AA and α-TOC potentiates As2O3 cytotoxicity in HL-60 cells, substantiated by depletion in antioxidant status, mitochondrial transmembrane potential, and inhibition of nuclear factor erythroid 2-related factor 2 and B-cell lymphoma 2 transcription factors. Mass spectrometry results showed decreased expression of proteins regulating cell cycle and translation in cells treated with As2O3, L-AA, and α-TOC when compared with As2O3-treated sample. In addition, this combination treatment identified numerous proteins associated with apoptosis and cell stress. HL-60 cells became more prone to As2O3 on exposure to L-AA and α-TOC, indicating that this combination may be a promising approach to increase the outcome of As2O3 chemotherapy.https://www.frontiersin.org/article/10.3389/fonc.2020.00065/fullacute promyelocytic leukemiaarsenic trioxideHL-60 cellsL-ascorbic acidα-tocopherol |
| spellingShingle | Radhakrishnan Chandraprabha Vineetha Radhakrishnan Chandraprabha Vineetha Sreedharan Hariharan Abdul Jaleel Mahesh Chandran Raveendran Harikumaran Nair L-Ascorbic Acid and α-Tocopherol Synergistically Triggers Apoptosis Inducing Antileukemic Effects of Arsenic Trioxide via Oxidative Stress in Human Acute Promyelocytic Leukemia Cells Frontiers in Oncology acute promyelocytic leukemia arsenic trioxide HL-60 cells L-ascorbic acid α-tocopherol |
| title | L-Ascorbic Acid and α-Tocopherol Synergistically Triggers Apoptosis Inducing Antileukemic Effects of Arsenic Trioxide via Oxidative Stress in Human Acute Promyelocytic Leukemia Cells |
| title_full | L-Ascorbic Acid and α-Tocopherol Synergistically Triggers Apoptosis Inducing Antileukemic Effects of Arsenic Trioxide via Oxidative Stress in Human Acute Promyelocytic Leukemia Cells |
| title_fullStr | L-Ascorbic Acid and α-Tocopherol Synergistically Triggers Apoptosis Inducing Antileukemic Effects of Arsenic Trioxide via Oxidative Stress in Human Acute Promyelocytic Leukemia Cells |
| title_full_unstemmed | L-Ascorbic Acid and α-Tocopherol Synergistically Triggers Apoptosis Inducing Antileukemic Effects of Arsenic Trioxide via Oxidative Stress in Human Acute Promyelocytic Leukemia Cells |
| title_short | L-Ascorbic Acid and α-Tocopherol Synergistically Triggers Apoptosis Inducing Antileukemic Effects of Arsenic Trioxide via Oxidative Stress in Human Acute Promyelocytic Leukemia Cells |
| title_sort | l ascorbic acid and α tocopherol synergistically triggers apoptosis inducing antileukemic effects of arsenic trioxide via oxidative stress in human acute promyelocytic leukemia cells |
| topic | acute promyelocytic leukemia arsenic trioxide HL-60 cells L-ascorbic acid α-tocopherol |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.00065/full |
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