Antitumor Activity of Ziziphus Jujube Fruit Extracts in KG-1 and NALM-6 Acute Leukemia Cell Lines
Abstract
Background: Ziziphus jujube Mill. belongs to the Rhamnaceae family. It has been reported to have a variety of biological activities such as antitumor, antioxidant, and anti-inflammatory effects. This study investigates the antiproliferative effect of Ziziphus jujube on KG-1 and NALM-6 acute leukemia cell lines.
Materials and Methods: In this experimental study, the aqueous, ethyl acetate, and hydroalcoholic extracts of the Ziziphus jujube were prepared. Total phenolic and flavonoid components were detected because the presence of these compounds is associated with antioxidant and anticancer effects. Different concentrations of extracts were prepared, and KG-1 and NALM-6 cell lines were treated with them at 12, 24, 36, and 48 hours. Cell viability and IC50 values of the extracts were calculated using MTT assays. BD Cycle TEST PLUS DNA Kit was used for cell cycle progression analysis. Bcl2, Bax, and caspase-3 mRNA expressions were also assessed.
Results: Cell viability decreased in a concentration-dependent manner. The best efficacy belonged to the ethyl acetate extract. Investigation of cell cycle progression demonstrated that the number of G0/G1 cells enhanced and the number of G2/M cells decreased when the ethyl acetate extract was applied in its IC50 concentration. A considerable increase in Caspase-3 and Bax and a decrease in Bcl2 gene expression were detected in molecular examination.
Conclusion: According to our research, Ziziphus jujube ethyl acetate extract has antitumor properties on KG-1 and NALM-6 cell lines, possibly through induction of apoptosis and cell cycle regulation.
1. William B. Ershler, Kenneth Kaushansky, Marshal A. Litchtman, Josef T. Prchal, Marcel M. Levi, Oliver W. Press, Linda J. Burns, Michael A. Caligiuri.Williams Hematology. 9th edn. Mc Graw Hill: New York, 2016.
2. Bassan R, Gatta G, Tondini C, et al. Adult acute lymphoblastic leukaemia. Crit Rev Oncol Hematol. 2004;50(3):223-61.
3. Richard A. McPherson, Matthew R. Pincus. Henry. Clinical Diagnosis and Management by Laboratory Method, 23nd edn. ELSEVIER: USA, 2017.
4. Ross ME, Mahfouz R, Onciu M, et al. Gene expression profiling of pediatric acute myelogenous leukemia. Blood. 2004;104(12):3679-87.
5. A Victor Hoffbrand, Douglas R Higgs, David M Keeling, Atual B Mehta. Postgraduate Haematology,7th edn. Wiley Blackwell:UK,2016.
6. Fattahi S, Ardekani AM, Zabihi E, et al. Antioxidant and apoptotic effects of an aqueous extract of Urtica dioica on the MCF-7 human breast cancer cell line. Asian Pac J Cancer Prev. 2013;14(9):5317-23.
7. Otles S, Yalcin B. Phenolic compounds analysis of root, stalk, and leaves of nettle. ScientificWorldJournal. 2012; 2012: 564367.
8. Bai L, Zhang H, Liu Q, et al. Chemical characterization of the main bioactive constituents from fruits of Ziziphus jujuba. Food Funct. 2016 5;7(6):2870-7.
9. Choi SH, Ahn JB, Kim HJ, et al. Changes in free amino acid, protein, and flavonoid content in jujube (Ziziphus jujube) fruit during eight stages of growth and antioxidative and cancer cell inhibitory effects by extracts. J Agric Food Chem.2012;60(41):10245-55.
10. Huang X, Kojima-Yuasa A, Xu S, et al. Combination of Zizyphus jujuba and green tea extracts exerts excellent cytotoxic activity in HepG2 cells via reducing the expression of APRIL. Am J Chin Med. 2009;37(1):169-79.
11. Jafarian A, Zolfaghari B, Shirani K. Cytotoxicity of different extracts of arial parts of Ziziphus spina-christi on Hela and MDA-MB-468 tumor cells. Adv Biomed Res. 2014;3:38.
12. Periasamy S, Liu CT, Wu WH, et al. Dietary Ziziphus jujuba fruit influence on aberrant crypt formation and blood cells in colitis-associated colorectal cancer in mice. Asian Pac J Cancer Prev. 2015;16(17):7561-6.
13. Vahedi F, Najafi MF, Bozari K. Evaluation of inhibitory effect and apoptosis induction of Zyzyphus Jujube on tumor cell lines, an in vitro preliminary study. Cytotechnology.2008;56(2):105-11.
14. Huang X, Kojima-Yuasa A, Xu S, et al. Green tea extract enhances the selective cytotoxic activity of Zizyphus jujuba extracts in HepG2 cells. Am J Chin Med. 2008;36(4):729-44.
15. Huang X, Kojima-Yuasa A, Norikura T, et al. Mechanism of the anti-cancer activity of Zizyphus jujuba in HepG2 cells. Am J Chin Med. 2007;35(3):517-32.
16. Huang X. Mechanism of the growth inhibitory effects of Zizyphus jujuba and green tea extracts in human hepatoma cells: Thesis, Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Japan; 2008.
17. Plastina P, Bonofiglio D, Vizza D, et al. Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. J Ethnopharmacol. 2012;140(2):325-32.
18. Ji X, Hou C, Gao Y, et al. Metagenomic analysis of gut microbiota modulatory effects of jujube (Ziziphus jujuba Mill.) polysaccharides in a colorectal cancer mouse model. Food Funct. 2020;11(1):163-173.
19. Shin M, Lee BM, Kim O, et al. Triterpenoids from Ziziphus jujuba induce apoptotic cell death in human 1. William B. Ershler, Kenneth Kaushansky, Marshal A. Litchtman, Josef T. Prchal, Marcel M. Levi, Oliver W. Press, Linda J. Burns, Michael A. Caligiuri.Williams Hematology. 9th edn. Mc Graw Hill: New York, 2016.
2. Bassan R, Gatta G, Tondini C, et al. Adult acute lymphoblastic leukaemia. Crit Rev Oncol Hematol. 2004;50(3):223-61.
3. Richard A. McPherson, Matthew R. Pincus. Henry. Clinical Diagnosis and Management by Laboratory Method, 23nd edn. ELSEVIER: USA, 2017.
4. Ross ME, Mahfouz R, Onciu M, et al. Gene expression profiling of pediatric acute myelogenous leukemia. Blood. 2004;104(12):3679-87.
5. A Victor Hoffbrand, Douglas R Higgs, David M Keeling, Atual B Mehta. Postgraduate Haematology,7th edn. Wiley Blackwell:UK,2016.
6. Fattahi S, Ardekani AM, Zabihi E, et al. Antioxidant and apoptotic effects of an aqueous extract of Urtica dioica on the MCF-7 human breast cancer cell line. Asian Pac J Cancer Prev. 2013;14(9):5317-23.
7. Otles S, Yalcin B. Phenolic compounds analysis of root, stalk, and leaves of nettle. ScientificWorldJournal. 2012; 2012: 564367.
8. Bai L, Zhang H, Liu Q, et al. Chemical characterization of the main bioactive constituents from fruits of Ziziphus jujuba. Food Funct. 2016 5;7(6):2870-7.
9. Choi SH, Ahn JB, Kim HJ, et al. Changes in free amino acid, protein, and flavonoid content in jujube (Ziziphus jujube) fruit during eight stages of growth and antioxidative and cancer cell inhibitory effects by extracts. J Agric Food Chem.2012;60(41):10245-55.
10. Huang X, Kojima-Yuasa A, Xu S, et al. Combination of Zizyphus jujuba and green tea extracts exerts excellent cytotoxic activity in HepG2 cells via reducing the expression of APRIL. Am J Chin Med. 2009;37(1):169-79.
11. Jafarian A, Zolfaghari B, Shirani K. Cytotoxicity of different extracts of arial parts of Ziziphus spina-christi on Hela and MDA-MB-468 tumor cells. Adv Biomed Res. 2014;3:38.
12. Periasamy S, Liu CT, Wu WH, et al. Dietary Ziziphus jujuba fruit influence on aberrant crypt formation and blood cells in colitis-associated colorectal cancer in mice. Asian Pac J Cancer Prev. 2015;16(17):7561-6.
13. Vahedi F, Najafi MF, Bozari K. Evaluation of inhibitory effect and apoptosis induction of Zyzyphus Jujube on tumor cell lines, an in vitro preliminary study. Cytotechnology.2008;56(2):105-11.
14. Huang X, Kojima-Yuasa A, Xu S, et al. Green tea extract enhances the selective cytotoxic activity of Zizyphus jujuba extracts in HepG2 cells. Am J Chin Med. 2008;36(4):729-44.
15. Huang X, Kojima-Yuasa A, Norikura T, et al. Mechanism of the anti-cancer activity of Zizyphus jujuba in HepG2 cells. Am J Chin Med. 2007;35(3):517-32.
16. Huang X. Mechanism of the growth inhibitory effects of Zizyphus jujuba and green tea extracts in human hepatoma cells: Thesis, Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Japan; 2008.
17. Plastina P, Bonofiglio D, Vizza D, et al. Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. J Ethnopharmacol. 2012;140(2):325-32.
18. Ji X, Hou C, Gao Y, et al. Metagenomic analysis of gut microbiota modulatory effects of jujube (Ziziphus jujuba Mill.) polysaccharides in a colorectal cancer mouse model. Food Funct. 2020;11(1):163-173.
19. Shin M, Lee BM, Kim O, et al. Triterpenoids from Ziziphus jujuba induce apoptotic cell death in human cancer cells through mitochondrial reactive oxygen species production. Food Funct. 2018;9(7):3895-905.
20. Rahman MM, Khan MA. Anti-cancer potential of South Asian plants. Nat Prod Bioprospect. 2013;3(3):74-88.
21. Aboul-Enein AM, El-Ela FA, Shalaby EA, et al. Traditional medicinal plants research in Egypt: Studies of antioxidant and anticancer activities. J Med Plants Res. 2012;6(5):689-703.
22. Hoshyar R, Mohaghegh Z, Torabi N, et al. Antitumor activity of aqueous extract of Ziziphus jujube fruit in breast cancer: an in vitro and in vivo study. Asian Pac J Reprod. 2015;4(2):116-22.
23. Al-Saeedi AH, Al-Ghafri MTH, Hossain MA. Comparative evaluation of total phenols, flavonoids content and antioxidant potential of leaf and fruit extracts of Omani Ziziphus jujuba L. Pac Sci Rev A: Nat Sci Eng. 2016;18(1):78-83.
2. Bassan R, Gatta G, Tondini C, et al. Adult acute lymphoblastic leukaemia. Crit Rev Oncol Hematol. 2004;50(3):223-61.
3. Richard A. McPherson, Matthew R. Pincus. Henry. Clinical Diagnosis and Management by Laboratory Method, 23nd edn. ELSEVIER: USA, 2017.
4. Ross ME, Mahfouz R, Onciu M, et al. Gene expression profiling of pediatric acute myelogenous leukemia. Blood. 2004;104(12):3679-87.
5. A Victor Hoffbrand, Douglas R Higgs, David M Keeling, Atual B Mehta. Postgraduate Haematology,7th edn. Wiley Blackwell:UK,2016.
6. Fattahi S, Ardekani AM, Zabihi E, et al. Antioxidant and apoptotic effects of an aqueous extract of Urtica dioica on the MCF-7 human breast cancer cell line. Asian Pac J Cancer Prev. 2013;14(9):5317-23.
7. Otles S, Yalcin B. Phenolic compounds analysis of root, stalk, and leaves of nettle. ScientificWorldJournal. 2012; 2012: 564367.
8. Bai L, Zhang H, Liu Q, et al. Chemical characterization of the main bioactive constituents from fruits of Ziziphus jujuba. Food Funct. 2016 5;7(6):2870-7.
9. Choi SH, Ahn JB, Kim HJ, et al. Changes in free amino acid, protein, and flavonoid content in jujube (Ziziphus jujube) fruit during eight stages of growth and antioxidative and cancer cell inhibitory effects by extracts. J Agric Food Chem.2012;60(41):10245-55.
10. Huang X, Kojima-Yuasa A, Xu S, et al. Combination of Zizyphus jujuba and green tea extracts exerts excellent cytotoxic activity in HepG2 cells via reducing the expression of APRIL. Am J Chin Med. 2009;37(1):169-79.
11. Jafarian A, Zolfaghari B, Shirani K. Cytotoxicity of different extracts of arial parts of Ziziphus spina-christi on Hela and MDA-MB-468 tumor cells. Adv Biomed Res. 2014;3:38.
12. Periasamy S, Liu CT, Wu WH, et al. Dietary Ziziphus jujuba fruit influence on aberrant crypt formation and blood cells in colitis-associated colorectal cancer in mice. Asian Pac J Cancer Prev. 2015;16(17):7561-6.
13. Vahedi F, Najafi MF, Bozari K. Evaluation of inhibitory effect and apoptosis induction of Zyzyphus Jujube on tumor cell lines, an in vitro preliminary study. Cytotechnology.2008;56(2):105-11.
14. Huang X, Kojima-Yuasa A, Xu S, et al. Green tea extract enhances the selective cytotoxic activity of Zizyphus jujuba extracts in HepG2 cells. Am J Chin Med. 2008;36(4):729-44.
15. Huang X, Kojima-Yuasa A, Norikura T, et al. Mechanism of the anti-cancer activity of Zizyphus jujuba in HepG2 cells. Am J Chin Med. 2007;35(3):517-32.
16. Huang X. Mechanism of the growth inhibitory effects of Zizyphus jujuba and green tea extracts in human hepatoma cells: Thesis, Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Japan; 2008.
17. Plastina P, Bonofiglio D, Vizza D, et al. Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. J Ethnopharmacol. 2012;140(2):325-32.
18. Ji X, Hou C, Gao Y, et al. Metagenomic analysis of gut microbiota modulatory effects of jujube (Ziziphus jujuba Mill.) polysaccharides in a colorectal cancer mouse model. Food Funct. 2020;11(1):163-173.
19. Shin M, Lee BM, Kim O, et al. Triterpenoids from Ziziphus jujuba induce apoptotic cell death in human 1. William B. Ershler, Kenneth Kaushansky, Marshal A. Litchtman, Josef T. Prchal, Marcel M. Levi, Oliver W. Press, Linda J. Burns, Michael A. Caligiuri.Williams Hematology. 9th edn. Mc Graw Hill: New York, 2016.
2. Bassan R, Gatta G, Tondini C, et al. Adult acute lymphoblastic leukaemia. Crit Rev Oncol Hematol. 2004;50(3):223-61.
3. Richard A. McPherson, Matthew R. Pincus. Henry. Clinical Diagnosis and Management by Laboratory Method, 23nd edn. ELSEVIER: USA, 2017.
4. Ross ME, Mahfouz R, Onciu M, et al. Gene expression profiling of pediatric acute myelogenous leukemia. Blood. 2004;104(12):3679-87.
5. A Victor Hoffbrand, Douglas R Higgs, David M Keeling, Atual B Mehta. Postgraduate Haematology,7th edn. Wiley Blackwell:UK,2016.
6. Fattahi S, Ardekani AM, Zabihi E, et al. Antioxidant and apoptotic effects of an aqueous extract of Urtica dioica on the MCF-7 human breast cancer cell line. Asian Pac J Cancer Prev. 2013;14(9):5317-23.
7. Otles S, Yalcin B. Phenolic compounds analysis of root, stalk, and leaves of nettle. ScientificWorldJournal. 2012; 2012: 564367.
8. Bai L, Zhang H, Liu Q, et al. Chemical characterization of the main bioactive constituents from fruits of Ziziphus jujuba. Food Funct. 2016 5;7(6):2870-7.
9. Choi SH, Ahn JB, Kim HJ, et al. Changes in free amino acid, protein, and flavonoid content in jujube (Ziziphus jujube) fruit during eight stages of growth and antioxidative and cancer cell inhibitory effects by extracts. J Agric Food Chem.2012;60(41):10245-55.
10. Huang X, Kojima-Yuasa A, Xu S, et al. Combination of Zizyphus jujuba and green tea extracts exerts excellent cytotoxic activity in HepG2 cells via reducing the expression of APRIL. Am J Chin Med. 2009;37(1):169-79.
11. Jafarian A, Zolfaghari B, Shirani K. Cytotoxicity of different extracts of arial parts of Ziziphus spina-christi on Hela and MDA-MB-468 tumor cells. Adv Biomed Res. 2014;3:38.
12. Periasamy S, Liu CT, Wu WH, et al. Dietary Ziziphus jujuba fruit influence on aberrant crypt formation and blood cells in colitis-associated colorectal cancer in mice. Asian Pac J Cancer Prev. 2015;16(17):7561-6.
13. Vahedi F, Najafi MF, Bozari K. Evaluation of inhibitory effect and apoptosis induction of Zyzyphus Jujube on tumor cell lines, an in vitro preliminary study. Cytotechnology.2008;56(2):105-11.
14. Huang X, Kojima-Yuasa A, Xu S, et al. Green tea extract enhances the selective cytotoxic activity of Zizyphus jujuba extracts in HepG2 cells. Am J Chin Med. 2008;36(4):729-44.
15. Huang X, Kojima-Yuasa A, Norikura T, et al. Mechanism of the anti-cancer activity of Zizyphus jujuba in HepG2 cells. Am J Chin Med. 2007;35(3):517-32.
16. Huang X. Mechanism of the growth inhibitory effects of Zizyphus jujuba and green tea extracts in human hepatoma cells: Thesis, Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Japan; 2008.
17. Plastina P, Bonofiglio D, Vizza D, et al. Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. J Ethnopharmacol. 2012;140(2):325-32.
18. Ji X, Hou C, Gao Y, et al. Metagenomic analysis of gut microbiota modulatory effects of jujube (Ziziphus jujuba Mill.) polysaccharides in a colorectal cancer mouse model. Food Funct. 2020;11(1):163-173.
19. Shin M, Lee BM, Kim O, et al. Triterpenoids from Ziziphus jujuba induce apoptotic cell death in human cancer cells through mitochondrial reactive oxygen species production. Food Funct. 2018;9(7):3895-905.
20. Rahman MM, Khan MA. Anti-cancer potential of South Asian plants. Nat Prod Bioprospect. 2013;3(3):74-88.
21. Aboul-Enein AM, El-Ela FA, Shalaby EA, et al. Traditional medicinal plants research in Egypt: Studies of antioxidant and anticancer activities. J Med Plants Res. 2012;6(5):689-703.
22. Hoshyar R, Mohaghegh Z, Torabi N, et al. Antitumor activity of aqueous extract of Ziziphus jujube fruit in breast cancer: an in vitro and in vivo study. Asian Pac J Reprod. 2015;4(2):116-22.
23. Al-Saeedi AH, Al-Ghafri MTH, Hossain MA. Comparative evaluation of total phenols, flavonoids content and antioxidant potential of leaf and fruit extracts of Omani Ziziphus jujuba L. Pac Sci Rev A: Nat Sci Eng. 2016;18(1):78-83.
| Files | ||
| Issue | Vol 17, No 4 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v17i4.13917 | |
| Keywords | ||
| Ziziphus jujube; Acute leukemia; KG-1; NALM-6; Cell cycle; Caspase-3; Proto-oncogene proteins; c-bcl-2; Bax | ||
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How to Cite
1.
Mosadegh Manshadi S, Shams Ardekani MR. Antitumor Activity of Ziziphus Jujube Fruit Extracts in KG-1 and NALM-6 Acute Leukemia Cell Lines. Int J Hematol Oncol Stem Cell Res. 2023;17(4):257-266.
