Issue
Evaluation of anticancer, antioxidant activity and phenolic compounds of Artemisia absinthium L. Extract
Corresponding Author(s) : Ismail Koyuncu
Cellular and Molecular Biology,
Vol. 64 No. 3: Issue 3
Abstract
In the treatment of cancer, which remains a fatal disease, increasingly successful treatment rates of alternative therapies using the power of plants have directed the scientific world towards natural plant resources. This study aimed to examine the anti-cancer and antioxidant properties and identify the phenolic content of the methanolic extract obtained from Artemisia absinthium L. (AR) species, which is used as folk-medicine. The antioxidant activity of the extract was investigated using total phenolics, flavonoids, ABTS and CUPRAC methods. Phenolic component analysis of the plant extract was performed by LC-MS/MS. The anti-cancer property of AR extract was investigated on human colon (DLD-1), endometrium (ECC-1) cancer cells and embryonic kidney (HEK-293) cells. Cytotoxic effects were defined with MTT, apoptotic activity with DNA fragmentation ELISA and AO/EB fluorescent staining, the genotoxic effect with the comet assay and the intracellular oxidative status with TAS and TOS methods. As a result of the study, it was determined that AR extract showed an antioxidant effect, and as a result of the content analysis made with LC-MS/MS, phenolic components were determined, the most abundant being chlorogenic acid, followed by quinic acid, cinnamic acid, rhoifolin and malic acide. AR extract showed cytotoxic activity on DLD-1 and ECC-1 cancer cells, while the cytotoxic effect on HEK-293 cells was determined to be low. It was determined that by increasing the intracellular amount of free radicals on cancer cells, this led to DNA damage, which consequently led to apoptosis of the cancer cells.
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- Aseervatham GSB, Sivasudha T, Jeyadevi R, Ananth DA. Environmental factors and unhealthy lifestyle influence oxidative stress in humans”an overview. Environmental Science and Pollution Research. 2013; 20(7): 4356-4369.
- Anand P, Kunnumakara AB, Sundaram C et al. Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical research. 2008; 25(9): 2097-2116.
- Xu D-P, Li Y, Meng X et al. Natural antioxidants in foods and medicinal plants: Extraction, assessment and resources. International journal of molecular sciences. 2017; 18(1): 96.
- Kasote DM, Katyare SS, Hegde MV, Bae H. Significance of antioxidant potential of plants and its relevance to therapeutic applications. International journal of biological sciences. 2015; 11(8): 982.
- Fridlender M, Kapulnik Y, Koltai H. Plant derived substances with anti-cancer activity: from folklore to practice. Frontiers in plant science. 2015; 6.
- Nasri H, Baradaran A, Shirzad H, Rafieian-Kopaei M. New concepts in nutraceuticals as alternative for pharmaceuticals. International journal of preventive medicine. 2014; 5(12): 1487.
- Greenwell M, Rahman P. Medicinal plants: their use in anticancer treatment. International journal of pharmaceutical sciences and research. 2015; 6(10): 4103.
- Sak K. Chemotherapy and dietary phytochemical agents. Chemotherapy research and practice. 2012; 2012.
- Liu B, Ezeogu L, Zellmer L, Yu B, Xu N, Joshua Liao D. Protecting the normal in order to better kill the cancer. Cancer medicine. 2015; 4(9): 1394-1403.
- Desai AG, Qazi GN, Ganju RK et al. Medicinal plants and cancer chemoprevention. Current drug metabolism. 2008; 9(7): 581-591.
- Solowey E, Lichtenstein M, Sallon S, Paavilainen H, Solowey E, Lorberboum-Galski H. Evaluating medicinal plants for anticancer activity. The Scientific World Journal. 2014; 2014.
- Prakash O, Kumar A, Kumar P. Anticancer potential of plants and natural products: a review. American Journal of Pharmacological Sciences. 2013; 1(6): 104-115.
- Ahmad R, Ahmad N, Naqvi AA, Shehzad A, Al-Ghamdi MS. Role of traditional Islamic and Arabic plants in cancer therapy. Journal of traditional and complementary medicine. 2017; 7(2): 195-204.
- Boik J. Natural compounds in cancer therapy. 2001.
- Omeje EO, Ahomafor JE, Onyekaba TU et al. Endophytic Fungi as Alternative and Reliable Sources for Potent Anticancer Agents. Natural Products and Cancer Drug Discovery: InTech; 2017.
- Boss A, Bishop KS, Marlow G, Barnett MP, Ferguson LR. Evidence to support the Anti-Cancer effect of olive leaf extract and future Directions. Nutrients. 2016; 8(8): 513.
- Altemimi A, Lakhssassi N, Baharlouei A, Watson DG, Lightfoot DA. Phytochemicals: Extraction, Isolation, and Identification of Bioactive Compounds from Plant Extracts. Plants. 2017; 6(4): 42.
- DíœLGER B, CEYLAN M, ALITSAOUS M, UćžURLU E. Antimicrobial Activity of Artemisia absinthium L. Turkish Journal of Biology. 1999; 23(3): 377-384.
- Yaşar S, Güler G, Beram A, Coşkun D, Ozansoy D. Acı Yavşan Otu (Artemisia absinthium L.) Yaprak Uçucu Bileşenleri. Mehmet Akif Ersoy íœniversitesi Fen Bilimleri Enstitüsü Dergisi. 2017; 8: 148-152.
- Tayarani-Najaran Z, Makki F-S, Alamolhodaei N-S, Mojarrab M, Emami SA. Cytotoxic and apoptotic effects of different extracts of Artemisia biennis Willd. on K562 and HL-60 cell lines. Iranian journal of basic medical sciences. 2017; 20(2): 166.
- Goud BJ, Swamy B. A review on history, controversy, traditional use, ethnobotany, phytochemistry and pharmacology of Artemisia absinthium Linn. International Journal of Advanced Research in Engineering and Applied Sciences. 2015; 4(5): 77-107.
- Shafi G, Hasan TN, Syed NA et al. Artemisia absinthium (AA): a novel potential complementary and alternative medicine for breast cancer. Molecular biology reports. 2012; 39(7): 7373-7379.
- Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food chemistry. 1999; 64(4): 555-559.
- Apak R, Guclu K, Ozyurek M, Karademir SE. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. Journal of agricultural and food chemistry. Dec 29 2004; 52(26): 7970-7981.
- Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental cell research. 1988; 175(1): 184-191.
- Kocyigit A, Koyuncu I, Taskin A, Dikilitas M, Bahadori F, Turkkan B. Antigenotoxic and antioxidant potentials of newly derivatized compound naringenin-oxime relative to naringenin on human mononuclear cells. Drug and chemical toxicology. 2016; 39(1): 66-73.
- Kocyigit A, Koyuncu I, Taskin A, Dikilitas M, Bahadori F, Turkkan B. Antigenotoxic and antioxidant potentials of newly derivatized compound naringenin-oxime relative to naringenin on human mononuclear cells. Drug and chemical toxicology. 2016; 39(1): 66-73.
- Liu K, Liu P-c, Liu R, Wu X. Dual AO/EB staining to detect apoptosis in osteosarcoma cells compared with flow cytometry. Medical science monitor basic research. 2015; 21: 15.
- Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. Dec 2005; 38(12): 1103-1111.
- Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical biochemistry. Apr 2004; 37(4): 277-285.
- Mesicek N, Perpar M. Essential oils from the orpine, Sedum maximum. Farmacevtski Vestnik. 1973; 24: 123-124.
- Orhan I, Deliorman-Orhan D, í–zçelik B. Antiviral activity and cytotoxicity of the lipophilic extracts of various edible plants and their fatty acids. Food chemistry. 2009; 115(2): 701-705.
- Yaylı N, Yaşar A, Yılmaz ć°skender N et al. Chemical constituents and antimicrobial activities of the essential oils from Sedum pallidum var. bithynicum and S. spurium grown in Turkey. Pharmaceutical biology. 2010; 48(2): 191-194.
- Kim S-J, Cho AR, Han J. Antioxidant and antimicrobial activities of leafy green vegetable extracts and their applications to meat product preservation. Food Control. 2013; 29(1): 112-120.
- Ginsburg H, Deharo E. A call for using natural compounds in the development of new antimalarial treatments–an introduction. Malaria Journal. 2011; 10(1): S1.
- Venugopal R, Liu RH. Phytochemicals in diets for breast cancer prevention: The importance of resveratrol and ursolic acid. Food Science and Human Wellness. 2012; 1(1): 1-13.
- Działo M, Mierziak J, Korzun U, Preisner M, Szopa J, Kulma A. The potential of plant phenolics in prevention and therapy of skin disorders. International journal of molecular sciences. 2016; 17(2): 160.
- Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacognosy reviews. 2010; 4(8): 118.
- Tyus CM. Anthocyanins from Norton pomace and color stability analysis for use as a colorant in plain Greek yogurt, University of Missouri--Columbia; 2014.
- Shukla S, Meeran SM, Katiyar SK. Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention. Cancer letters. 2014; 355(1): 9-17.
- Aghajanpour M, Nazer MR, Obeidavi Z, Akbari M, Ezati P, Kor NM. Functional foods and their role in cancer prevention and health promotion: a comprehensive review. American journal of cancer research. 2017; 7(4): 740.
- Wahle KW, Brown I, Rotondo D, Heys SD. Plant phenolics in the prevention and treatment of cancer. Bio-Farms for Nutraceuticals. 2010: 36-51.
- Wang H, Oo Khor T, Shu L et al. Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2012; 12(10): 1281-1305.
- Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. The Scientific World Journal. 2013; 2013.
- Ozcan T, Akpinar-Bayizit A, Yilmaz-Ersan L, Delikanli B. Phenolics in human health. International Journal of chemical Engineering and applications. 2014; 5(5): 393.
- Velioglu Y, Mazza G, Gao L, Oomah B. Antioxidant activity and total phenolics in selected fruits, vegetables, and grain products. Journal of agricultural and food chemistry. 1998; 46(10): 4113-4117.
- Kordali S, Kotan R, Mavi A, Cakir A, Ala A, Yildirim A. Determination of the chemical composition and antioxidant activity of the essential oil of Artemisia dracunculus and of the antifungal and antibacterial activities of Turkish Artemisia absinthium, A. dracunculus, Artemisia santonicum, and Artemisia spicigera essential oils. Journal of agricultural and food chemistry. 2005; 53(24): 9452-9458.
- Sengul M, Ercisli S, Yildiz H, Gungor N, Kavaz A, í‡etin B. Antioxidant, antimicrobial activity and total phenolic content within the aerial parts of Artemisia absinthum, Artemisia santonicum and Saponaria officinalis. Iranian journal of pharmaceutical research: IJPR. 2011; 10(1): 49.
- Higdon JV, Frei B. Coffee and health: a review of recent human research. Critical reviews in food science and nutrition. 2006; 46(2): 101-123.
- Bonita JS, Mandarano M, Shuta D, Vinson J. Coffee and cardiovascular disease: in vitro, cellular, animal, and human studies. Pharmacological research. 2007; 55(3): 187-198.
- Darwiche N, El-Banna S, Gali-Muhtasib H. Cell cycle modulatory and apoptotic effects of plant-derived anticancer drugs in clinical use or development. Expert opinion on drug discovery. 2007; 2(3): 361-379.
- Lee JH, Khor TO, Shu L, Su Z-Y, Fuentes F, Kong A-NT. Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and progression. Pharmacology & therapeutics. 2013; 137(2): 153-171.
- Araújo JR, Gonçalves P, Martel F. Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines. Nutrition Research. 2011; 31(2): 77-87.
References
Aseervatham GSB, Sivasudha T, Jeyadevi R, Ananth DA. Environmental factors and unhealthy lifestyle influence oxidative stress in humans”an overview. Environmental Science and Pollution Research. 2013; 20(7): 4356-4369.
Anand P, Kunnumakara AB, Sundaram C et al. Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical research. 2008; 25(9): 2097-2116.
Xu D-P, Li Y, Meng X et al. Natural antioxidants in foods and medicinal plants: Extraction, assessment and resources. International journal of molecular sciences. 2017; 18(1): 96.
Kasote DM, Katyare SS, Hegde MV, Bae H. Significance of antioxidant potential of plants and its relevance to therapeutic applications. International journal of biological sciences. 2015; 11(8): 982.
Fridlender M, Kapulnik Y, Koltai H. Plant derived substances with anti-cancer activity: from folklore to practice. Frontiers in plant science. 2015; 6.
Nasri H, Baradaran A, Shirzad H, Rafieian-Kopaei M. New concepts in nutraceuticals as alternative for pharmaceuticals. International journal of preventive medicine. 2014; 5(12): 1487.
Greenwell M, Rahman P. Medicinal plants: their use in anticancer treatment. International journal of pharmaceutical sciences and research. 2015; 6(10): 4103.
Sak K. Chemotherapy and dietary phytochemical agents. Chemotherapy research and practice. 2012; 2012.
Liu B, Ezeogu L, Zellmer L, Yu B, Xu N, Joshua Liao D. Protecting the normal in order to better kill the cancer. Cancer medicine. 2015; 4(9): 1394-1403.
Desai AG, Qazi GN, Ganju RK et al. Medicinal plants and cancer chemoprevention. Current drug metabolism. 2008; 9(7): 581-591.
Solowey E, Lichtenstein M, Sallon S, Paavilainen H, Solowey E, Lorberboum-Galski H. Evaluating medicinal plants for anticancer activity. The Scientific World Journal. 2014; 2014.
Prakash O, Kumar A, Kumar P. Anticancer potential of plants and natural products: a review. American Journal of Pharmacological Sciences. 2013; 1(6): 104-115.
Ahmad R, Ahmad N, Naqvi AA, Shehzad A, Al-Ghamdi MS. Role of traditional Islamic and Arabic plants in cancer therapy. Journal of traditional and complementary medicine. 2017; 7(2): 195-204.
Boik J. Natural compounds in cancer therapy. 2001.
Omeje EO, Ahomafor JE, Onyekaba TU et al. Endophytic Fungi as Alternative and Reliable Sources for Potent Anticancer Agents. Natural Products and Cancer Drug Discovery: InTech; 2017.
Boss A, Bishop KS, Marlow G, Barnett MP, Ferguson LR. Evidence to support the Anti-Cancer effect of olive leaf extract and future Directions. Nutrients. 2016; 8(8): 513.
Altemimi A, Lakhssassi N, Baharlouei A, Watson DG, Lightfoot DA. Phytochemicals: Extraction, Isolation, and Identification of Bioactive Compounds from Plant Extracts. Plants. 2017; 6(4): 42.
DíœLGER B, CEYLAN M, ALITSAOUS M, UćžURLU E. Antimicrobial Activity of Artemisia absinthium L. Turkish Journal of Biology. 1999; 23(3): 377-384.
Yaşar S, Güler G, Beram A, Coşkun D, Ozansoy D. Acı Yavşan Otu (Artemisia absinthium L.) Yaprak Uçucu Bileşenleri. Mehmet Akif Ersoy íœniversitesi Fen Bilimleri Enstitüsü Dergisi. 2017; 8: 148-152.
Tayarani-Najaran Z, Makki F-S, Alamolhodaei N-S, Mojarrab M, Emami SA. Cytotoxic and apoptotic effects of different extracts of Artemisia biennis Willd. on K562 and HL-60 cell lines. Iranian journal of basic medical sciences. 2017; 20(2): 166.
Goud BJ, Swamy B. A review on history, controversy, traditional use, ethnobotany, phytochemistry and pharmacology of Artemisia absinthium Linn. International Journal of Advanced Research in Engineering and Applied Sciences. 2015; 4(5): 77-107.
Shafi G, Hasan TN, Syed NA et al. Artemisia absinthium (AA): a novel potential complementary and alternative medicine for breast cancer. Molecular biology reports. 2012; 39(7): 7373-7379.
Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food chemistry. 1999; 64(4): 555-559.
Apak R, Guclu K, Ozyurek M, Karademir SE. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. Journal of agricultural and food chemistry. Dec 29 2004; 52(26): 7970-7981.
Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental cell research. 1988; 175(1): 184-191.
Kocyigit A, Koyuncu I, Taskin A, Dikilitas M, Bahadori F, Turkkan B. Antigenotoxic and antioxidant potentials of newly derivatized compound naringenin-oxime relative to naringenin on human mononuclear cells. Drug and chemical toxicology. 2016; 39(1): 66-73.
Kocyigit A, Koyuncu I, Taskin A, Dikilitas M, Bahadori F, Turkkan B. Antigenotoxic and antioxidant potentials of newly derivatized compound naringenin-oxime relative to naringenin on human mononuclear cells. Drug and chemical toxicology. 2016; 39(1): 66-73.
Liu K, Liu P-c, Liu R, Wu X. Dual AO/EB staining to detect apoptosis in osteosarcoma cells compared with flow cytometry. Medical science monitor basic research. 2015; 21: 15.
Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. Dec 2005; 38(12): 1103-1111.
Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical biochemistry. Apr 2004; 37(4): 277-285.
Mesicek N, Perpar M. Essential oils from the orpine, Sedum maximum. Farmacevtski Vestnik. 1973; 24: 123-124.
Orhan I, Deliorman-Orhan D, í–zçelik B. Antiviral activity and cytotoxicity of the lipophilic extracts of various edible plants and their fatty acids. Food chemistry. 2009; 115(2): 701-705.
Yaylı N, Yaşar A, Yılmaz ć°skender N et al. Chemical constituents and antimicrobial activities of the essential oils from Sedum pallidum var. bithynicum and S. spurium grown in Turkey. Pharmaceutical biology. 2010; 48(2): 191-194.
Kim S-J, Cho AR, Han J. Antioxidant and antimicrobial activities of leafy green vegetable extracts and their applications to meat product preservation. Food Control. 2013; 29(1): 112-120.
Ginsburg H, Deharo E. A call for using natural compounds in the development of new antimalarial treatments–an introduction. Malaria Journal. 2011; 10(1): S1.
Venugopal R, Liu RH. Phytochemicals in diets for breast cancer prevention: The importance of resveratrol and ursolic acid. Food Science and Human Wellness. 2012; 1(1): 1-13.
Działo M, Mierziak J, Korzun U, Preisner M, Szopa J, Kulma A. The potential of plant phenolics in prevention and therapy of skin disorders. International journal of molecular sciences. 2016; 17(2): 160.
Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacognosy reviews. 2010; 4(8): 118.
Tyus CM. Anthocyanins from Norton pomace and color stability analysis for use as a colorant in plain Greek yogurt, University of Missouri--Columbia; 2014.
Shukla S, Meeran SM, Katiyar SK. Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention. Cancer letters. 2014; 355(1): 9-17.
Aghajanpour M, Nazer MR, Obeidavi Z, Akbari M, Ezati P, Kor NM. Functional foods and their role in cancer prevention and health promotion: a comprehensive review. American journal of cancer research. 2017; 7(4): 740.
Wahle KW, Brown I, Rotondo D, Heys SD. Plant phenolics in the prevention and treatment of cancer. Bio-Farms for Nutraceuticals. 2010: 36-51.
Wang H, Oo Khor T, Shu L et al. Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2012; 12(10): 1281-1305.
Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. The Scientific World Journal. 2013; 2013.
Ozcan T, Akpinar-Bayizit A, Yilmaz-Ersan L, Delikanli B. Phenolics in human health. International Journal of chemical Engineering and applications. 2014; 5(5): 393.
Velioglu Y, Mazza G, Gao L, Oomah B. Antioxidant activity and total phenolics in selected fruits, vegetables, and grain products. Journal of agricultural and food chemistry. 1998; 46(10): 4113-4117.
Kordali S, Kotan R, Mavi A, Cakir A, Ala A, Yildirim A. Determination of the chemical composition and antioxidant activity of the essential oil of Artemisia dracunculus and of the antifungal and antibacterial activities of Turkish Artemisia absinthium, A. dracunculus, Artemisia santonicum, and Artemisia spicigera essential oils. Journal of agricultural and food chemistry. 2005; 53(24): 9452-9458.
Sengul M, Ercisli S, Yildiz H, Gungor N, Kavaz A, í‡etin B. Antioxidant, antimicrobial activity and total phenolic content within the aerial parts of Artemisia absinthum, Artemisia santonicum and Saponaria officinalis. Iranian journal of pharmaceutical research: IJPR. 2011; 10(1): 49.
Higdon JV, Frei B. Coffee and health: a review of recent human research. Critical reviews in food science and nutrition. 2006; 46(2): 101-123.
Bonita JS, Mandarano M, Shuta D, Vinson J. Coffee and cardiovascular disease: in vitro, cellular, animal, and human studies. Pharmacological research. 2007; 55(3): 187-198.
Darwiche N, El-Banna S, Gali-Muhtasib H. Cell cycle modulatory and apoptotic effects of plant-derived anticancer drugs in clinical use or development. Expert opinion on drug discovery. 2007; 2(3): 361-379.
Lee JH, Khor TO, Shu L, Su Z-Y, Fuentes F, Kong A-NT. Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and progression. Pharmacology & therapeutics. 2013; 137(2): 153-171.
Araújo JR, Gonçalves P, Martel F. Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines. Nutrition Research. 2011; 31(2): 77-87.