Research Article
Histone deacetylase inhibitory and antioxidant activities of some ethanolic plant extracts: A novel therapeutic approach for cancer
Abstract
Purpose: The aim of this study was to evaluate histone deacetylase inhibitory and antioxidant activities of some ethanolic plant extracts.
Materials and Methods: In this study, the inhibitory effects of ethyl alcohol extracts prepared from various plants and some chemical compounds on histone deacetylase activity were investigated. In addition, the antioxidant activity of plant-derived active substances, which have had an important value in alternative medicine in recent years, has been determined to replace chemicals.
Results: All the plant extracts and chemical substances used in the study showed histone deacetylase inhibitory effect (with IC50 range of 0.000078-319.0 µg/mL) and antioxidant activity. The results indicated that the percentage of histone deacetylase inhibition and antioxidant activities increased with increasing concentrations of the plant extracts and chemical compounds.
Conclusion: These plant extracts which are potential sources of histone deacetylase inhibitors may be appropriately used as an alternative support to drug treatment rather than the use of toxic chemicals.
References
- Yang S, Huang Y, Zhao Q. Epigenetic alterations and inflammation as emerging use for the advancement of treatment in non-small cell lung cancer. Front Immunol. 2022;13:878740.
- Huynh NCN, Everts V, Ampornaramveth RS. Histone deacetylases and their roles in mineralized tissue regeneration. Bone Rep. 2017;7:33–40.
- Kalin JH, Wu M, Gomez AV, Song Y, Das J, Hayward D et al. Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors. Nat Commun. 2018;9:53.
- Chen D, Shen A, Fang G, Liu H, Zhang M, Tang S et al. Tetrahydroisoquinolines as novel histone deacetylase inhibitors for treatment of cancer. Acta Pharm Sin B. 2016;6:93–9.
- Cerna T, Hrabeta J, Eckschlager T, Frei E, Schmeiser H, Arlt V et al. The histone deacetylase inhibitor valproic acid exerts a synergistic cytotoxicity with the DNA-damaging drug ellipticine in neuroblastoma cells. Int J Mol Sci. 2018;19:164.
- Wang Y, Abrol R, Mak JYW, Das Gupta K, Ramnath D, Karunakaran D et al. Histone deacetylase 7: A signalling hub controlling development, inflammation, metabolism and disease. FEBS J. 2023;290:2805-32.
- Chittur SV, Sangster-Guity N, McCormick PJ. Histone deacetylase inhibitors: A new mode for inhibition of cholesterol metabolism. BMC Genomics. 2008;9:507.
- Mottamal M, Zheng S, Huang T, Wang G. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules. 2015;20:3898–941.
- Witt O, Deubzer HE, Milde T, Oehme I. HDAC family: What are the cancer relevant targets? Cancer Lett. 2009;277:8–21.
- Cai MH, Xu XG, Yan SL, Sun Z, Ying Y, Wang BK et al. Depletion of HDAC1, 7 and 8 by histone deacetylase inhibition confers elimination of pancreatic cancer stem cells in combination with gemcitabine. Sci Rep. 2018;8:1621.
- Tapadar S, Fathi S, Raji I, Omesiete W, Kornacki JR, Mwakwari SC et al. A structure–activity relationship of non-peptide macrocyclic histone deacetylase inhibitors and their anti-proliferative and anti-inflammatory activities. Bioorg Med Chem. 2015;23:7543–64.
- Markozashvili D, Pichugin A, Barat A, Camara-Clayette V, Vasilyeva NV, Lelièvre H et al. Histone deacetylase inhibitor abexinostat affects chromatin organization and gene transcription in normal B cells and in mantle cell lymphoma. Gene. 2016;580:134–43.
- Ranganathan P, Hamad R, Mohamed R, Jayakumar C, Muthusamy T, Ramesh G. Histone deacetylase–mediated silencing of AMWAP expression contributes to cisplatin nephrotoxicity. Kidney Int. 2016;89:317–26.
- Marks PA, Richon VM, Rifkind RA. Histone deacetylase inhibitors: Inducers of differentiation or apoptosis of transformed cells. JNCI J Natl Cancer Inst. 2000;92:1210–6.
- Eckschlager T, Plch J, Stiborova M, Hrabeta J. Histone deacetylase inhibitors as anticancer drugs. Int J Mol Sci. 2017;18:1414.
- Ashwini N, Garg M, Mohan CD, Fuchs JE, Rangappa S, Anusha S et al. Synthesis of 1,2-benzisoxazole tethered 1,2,3-triazoles that exhibit anticancer activity in acute myeloid leukemia cell lines by inhibiting histone deacetylases, and inducing p21 and tubulin acetylation. Bioorg Med Chem. 2015;23:6157–65.
- Bayrak BB, Yanardag R. Histone deacetylase, xanthine oxidase and urease inhibitory activities of Eremurus spectabilis M. Bieb. extracts. Experimed. 2021;11:156-61.
- Brand-Williams W, Cuvelier ME, Berset C. Use of a free radical method to evaluate antioxidant activity. Leb Wiss Technol - Food Sci Technol. 1995;28:25–30.
- Arnao MB, Cano A, Acosta M. The hydrophilic and lipophilic contribution to total antioxidant activity. Food Chem. 2001;73:239–44.
- Oyaizu M. Studies on products of browning reaction. Antioxidative activities of products of browning reaction prepared from glucosamine. Japanese J Nutr Diet. 1986;44:307–15.
- George BP, Chandran R, Abrahamse H. Role of phytochemicals in cancer chemoprevention: Insights. Antioxidants. 2021;10:1455.
- Ikeda Y, Nagase N, Tsuji A, Taniguchi K, Kitagishi Y, Matsuda S. Comprehension of the relationship between autophagy and reactive oxygen species for superior cancer therapy with histone deacetylase inhibitors. Oxygen. 2021;1:22–31.
- Abbas A, Gupta S. The role of histone deacetylases in prostate cancer. Epigenetics. 2008;3:300–9.
- Turrini E, Ferruzzi L, Fimognari C. Potential effects of pomegranate polyphenols in cancer prevention and therapy. Oxid Med Cell Longev. 2015;2015:1–19.
- Teniente SL, Flores-Gallegos AC, Esparza-González SC, Campos-Múzquiz LG, Nery-Flores SD, Rodríguez-Herrera R. Anticancer effect of pomegranate peel polyphenols against cervical cancer. Antioxidants. 2023;12:127.
- Albrecht M, Jiang W, Kumi-Diaka J, Lansky EP, Gommersall LM, Patel A et al. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J Med Food. 2004;7:274–83.
- Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci. 2005;102:14813–8.
- Wei X, Xia L, Ziyayiding D, Chen Q, Liu R, Xu X et al. The extracts of Artemisia absinthium L. suppress the growth of hepatocellular carcinoma cells through induction of apoptosis via endoplasmic reticulum stress and mitochondrial-dependent pathway. Molecules. 2019;24:913.
- Shafi G, Hasan TN, Syed NA, Al-Hazzani AA, Alshatwi AA, Jyothi A et al. Artemisia absinthium (AA): A novel potential complementary and alternative medicine for breast cancer. Mol Biol Rep. 2012;39:7373–9.
- Qiu X, Zhu L, Wang H, Tan Y, Yang Z, Yang L et al. From natural products to HDAC inhibitors: An overview of drug discovery and design strategy. Bioorg Med Chem. 2021;2021:52.
- Ayoka TO, Ezema BO, Eze CN, Nnadi CO. Antioxidants for the prevention and treatment of non-communicable diseases. J Explor Res Pharmacol. 2022;7:178–88.
- Zheng GQ. Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med. 1994;60:54–7.
- Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 1996;20:933–56.
- Pyo YH, Lee TC, Logendra L, Rosen RT. Antioxidant activity and phenolic compounds of Swiss chard (Beta vulgaris subspecies cycla) extracts. Food Chem. 2004;85:19–26.
- Kordali S, Cakir A, Mavi A, Kilic H, Yildirim A. Screening of chemical composition and antifungal and antioxidant activities of the essential oils from three Turkish artemisia species. J Agric Food Chem. 2005;53:1408–16.
- Bisht D, Kumar D, Kumar D, Dua K, Chellappan DK. Phytochemistry and pharmacological activity of the genus artemisia. Arch Pharm Res. 2021;44:439–74.
- Proestos C, Lytoudi K, Mavromelanidou O, Zoumpoulakis P, Sinanoglou V. Antioxidant capacity of selected plant extracts and their essential oils. Antioxidants. 2013;2:11–22.
Bazı etanolik bitki ekstrelerinin histon deasetilaz inhibitör ve antioksidan aktiviteleri: Kanser için yeni bir terapötik yaklaşım
Abstract
Amaç: Bu çalışmanın amacı, bazı etanolik bitki ekstraktlarının histon deasetilaz inhibitörü ve antioksidan aktivitelerini değerlendirmektir.
Gereç ve Yöntem: Bu çalışmada, çeşitli bitkilerden hazırlanan etil alkollü ekstrelerin ve bazı kimyasal bileşiklerin histon deasetilaz aktivitesi üzerindeki inhibitör etkileri araştırıldı. Ayrıca son yıllarda alternatif tıpta önemli bir değere sahip olan bitki kaynaklı aktif maddelerin, kimyasalların yerini alması için antioksidan aktivitesi de tayin edildi.
Bulgular: Çalışmada kullanılan tüm bitki ekstreleri ve kimyasal maddeler histon deasetilazı inhibe edici etki (IC50 0.000078-319.0 µg/mL aralığında) ve antioksidan aktivite göstermiştir. Sonuçlar, histon deasetilaz inhibisyon yüzdesinin ve antioksidan aktivitelerinin, bitki ekstrelerinin ve kimyasal bileşiklerin artan konsantrasyonu ile arttığını göstermiştir.
Sonuç: Histon deasetilaz inhibitörlerinin potansiyel kaynakları olan bu bitki ekstrelerinin, toksik kimyasalların kullanımı yerine ilaç tedavisine alternatif bir destek olarak uygun şekilde kullanılabileceği önerilebilir.
References
- Yang S, Huang Y, Zhao Q. Epigenetic alterations and inflammation as emerging use for the advancement of treatment in non-small cell lung cancer. Front Immunol. 2022;13:878740.
- Huynh NCN, Everts V, Ampornaramveth RS. Histone deacetylases and their roles in mineralized tissue regeneration. Bone Rep. 2017;7:33–40.
- Kalin JH, Wu M, Gomez AV, Song Y, Das J, Hayward D et al. Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors. Nat Commun. 2018;9:53.
- Chen D, Shen A, Fang G, Liu H, Zhang M, Tang S et al. Tetrahydroisoquinolines as novel histone deacetylase inhibitors for treatment of cancer. Acta Pharm Sin B. 2016;6:93–9.
- Cerna T, Hrabeta J, Eckschlager T, Frei E, Schmeiser H, Arlt V et al. The histone deacetylase inhibitor valproic acid exerts a synergistic cytotoxicity with the DNA-damaging drug ellipticine in neuroblastoma cells. Int J Mol Sci. 2018;19:164.
- Wang Y, Abrol R, Mak JYW, Das Gupta K, Ramnath D, Karunakaran D et al. Histone deacetylase 7: A signalling hub controlling development, inflammation, metabolism and disease. FEBS J. 2023;290:2805-32.
- Chittur SV, Sangster-Guity N, McCormick PJ. Histone deacetylase inhibitors: A new mode for inhibition of cholesterol metabolism. BMC Genomics. 2008;9:507.
- Mottamal M, Zheng S, Huang T, Wang G. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules. 2015;20:3898–941.
- Witt O, Deubzer HE, Milde T, Oehme I. HDAC family: What are the cancer relevant targets? Cancer Lett. 2009;277:8–21.
- Cai MH, Xu XG, Yan SL, Sun Z, Ying Y, Wang BK et al. Depletion of HDAC1, 7 and 8 by histone deacetylase inhibition confers elimination of pancreatic cancer stem cells in combination with gemcitabine. Sci Rep. 2018;8:1621.
- Tapadar S, Fathi S, Raji I, Omesiete W, Kornacki JR, Mwakwari SC et al. A structure–activity relationship of non-peptide macrocyclic histone deacetylase inhibitors and their anti-proliferative and anti-inflammatory activities. Bioorg Med Chem. 2015;23:7543–64.
- Markozashvili D, Pichugin A, Barat A, Camara-Clayette V, Vasilyeva NV, Lelièvre H et al. Histone deacetylase inhibitor abexinostat affects chromatin organization and gene transcription in normal B cells and in mantle cell lymphoma. Gene. 2016;580:134–43.
- Ranganathan P, Hamad R, Mohamed R, Jayakumar C, Muthusamy T, Ramesh G. Histone deacetylase–mediated silencing of AMWAP expression contributes to cisplatin nephrotoxicity. Kidney Int. 2016;89:317–26.
- Marks PA, Richon VM, Rifkind RA. Histone deacetylase inhibitors: Inducers of differentiation or apoptosis of transformed cells. JNCI J Natl Cancer Inst. 2000;92:1210–6.
- Eckschlager T, Plch J, Stiborova M, Hrabeta J. Histone deacetylase inhibitors as anticancer drugs. Int J Mol Sci. 2017;18:1414.
- Ashwini N, Garg M, Mohan CD, Fuchs JE, Rangappa S, Anusha S et al. Synthesis of 1,2-benzisoxazole tethered 1,2,3-triazoles that exhibit anticancer activity in acute myeloid leukemia cell lines by inhibiting histone deacetylases, and inducing p21 and tubulin acetylation. Bioorg Med Chem. 2015;23:6157–65.
- Bayrak BB, Yanardag R. Histone deacetylase, xanthine oxidase and urease inhibitory activities of Eremurus spectabilis M. Bieb. extracts. Experimed. 2021;11:156-61.
- Brand-Williams W, Cuvelier ME, Berset C. Use of a free radical method to evaluate antioxidant activity. Leb Wiss Technol - Food Sci Technol. 1995;28:25–30.
- Arnao MB, Cano A, Acosta M. The hydrophilic and lipophilic contribution to total antioxidant activity. Food Chem. 2001;73:239–44.
- Oyaizu M. Studies on products of browning reaction. Antioxidative activities of products of browning reaction prepared from glucosamine. Japanese J Nutr Diet. 1986;44:307–15.
- George BP, Chandran R, Abrahamse H. Role of phytochemicals in cancer chemoprevention: Insights. Antioxidants. 2021;10:1455.
- Ikeda Y, Nagase N, Tsuji A, Taniguchi K, Kitagishi Y, Matsuda S. Comprehension of the relationship between autophagy and reactive oxygen species for superior cancer therapy with histone deacetylase inhibitors. Oxygen. 2021;1:22–31.
- Abbas A, Gupta S. The role of histone deacetylases in prostate cancer. Epigenetics. 2008;3:300–9.
- Turrini E, Ferruzzi L, Fimognari C. Potential effects of pomegranate polyphenols in cancer prevention and therapy. Oxid Med Cell Longev. 2015;2015:1–19.
- Teniente SL, Flores-Gallegos AC, Esparza-González SC, Campos-Múzquiz LG, Nery-Flores SD, Rodríguez-Herrera R. Anticancer effect of pomegranate peel polyphenols against cervical cancer. Antioxidants. 2023;12:127.
- Albrecht M, Jiang W, Kumi-Diaka J, Lansky EP, Gommersall LM, Patel A et al. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J Med Food. 2004;7:274–83.
- Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci. 2005;102:14813–8.
- Wei X, Xia L, Ziyayiding D, Chen Q, Liu R, Xu X et al. The extracts of Artemisia absinthium L. suppress the growth of hepatocellular carcinoma cells through induction of apoptosis via endoplasmic reticulum stress and mitochondrial-dependent pathway. Molecules. 2019;24:913.
- Shafi G, Hasan TN, Syed NA, Al-Hazzani AA, Alshatwi AA, Jyothi A et al. Artemisia absinthium (AA): A novel potential complementary and alternative medicine for breast cancer. Mol Biol Rep. 2012;39:7373–9.
- Qiu X, Zhu L, Wang H, Tan Y, Yang Z, Yang L et al. From natural products to HDAC inhibitors: An overview of drug discovery and design strategy. Bioorg Med Chem. 2021;2021:52.
- Ayoka TO, Ezema BO, Eze CN, Nnadi CO. Antioxidants for the prevention and treatment of non-communicable diseases. J Explor Res Pharmacol. 2022;7:178–88.
- Zheng GQ. Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med. 1994;60:54–7.
- Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 1996;20:933–56.
- Pyo YH, Lee TC, Logendra L, Rosen RT. Antioxidant activity and phenolic compounds of Swiss chard (Beta vulgaris subspecies cycla) extracts. Food Chem. 2004;85:19–26.
- Kordali S, Cakir A, Mavi A, Kilic H, Yildirim A. Screening of chemical composition and antifungal and antioxidant activities of the essential oils from three Turkish artemisia species. J Agric Food Chem. 2005;53:1408–16.
- Bisht D, Kumar D, Kumar D, Dua K, Chellappan DK. Phytochemistry and pharmacological activity of the genus artemisia. Arch Pharm Res. 2021;44:439–74.
- Proestos C, Lytoudi K, Mavromelanidou O, Zoumpoulakis P, Sinanoglou V. Antioxidant capacity of selected plant extracts and their essential oils. Antioxidants. 2013;2:11–22.
There are 37 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Medical Biochemistry - Proteins, Peptides and Proteomics |
| Journal Section | Research |
| Authors | |
| Early Pub Date | September 25, 2023 |
| Publication Date | September 30, 2023 |
| Acceptance Date | August 20, 2023 |
| Published in Issue | Year 2023 Volume: 48 Issue: 3 |
This journal is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.