Investigation of Cytotoxic Effect of Salvia pilifera Extracts and Synthetic Chlorogenic and Caffeic Acids on DU145 Prostate Cancer Cells Line
Öz
Salvia species have been used in the treatment of
many diseases due to their medical effects, and the effects of these species on
prostate cancer cells should be investigated in more detail. In this study, we
aimed to determine anti-carcinogenic activities of dichloromethane (DCM) and
methanol (MeOH) extracts of Salvia
pilifera and the synthetic chloregenic (CGA) and caffeic acids (CA) on
DU-145 prostate cancer cells. The cytotoxicity of extracts and synthetic
compounds on cell viability of DU-145 was measured by using MTT method.
Induction of apoptosis was tested by using Annexin V and 7ADD staining. DNA
fragmentation was evaluated in cells. Also, transcripton levels of Bax, Caspase
3, Caspase 9 and Bcl-2 and Bcl-xL genes were determined. Lastly, the phenolic
compounds in MeOH extract were determined by HPLC. In MTT test, extracts, CGA
and CA were found to be diminished proliferation of DU145 cells. However, in
apoptosis assay, no apoptotic activity for extract and synthetic compounds was
observed. In DNA fragmentation test, while no significant difference in
extracts group was observed as compared to controls, fragmentation as swab in
synthetic compound groups was observed. Small changes were observed in
transcription levels of apoptotic and antipoptotic genes. A total
of 11 phenolic acids were determined including fumaric acid, gallic acid,
gallocatechin, catechin, oleorufein, 4-hydroxybenzoic acid, caffeic acid,
syringic acid, ellagic acid, 3-hydroxy cinnamic acid and protocatechuic acid. Results of the present study suggest that S. pilifera extracts and synthetic CGA
and CA might have cytotoxic effects on DU145 cell at certain concentration (≥50
µg ml-1 for DCM;
≥ 100 µg ml-1 for
MeOH; ≥ 1 µg ml-1 for CGA
and CA) yet that these effects may be manifested through another pathway but
apoptosis.
Anahtar Kelimeler
S. pilifera extract Caffeic acid Chlorogenic acid Cytotoxicity Apoptosis Prostate cancer
Kaynakça
- Ali N, Rashid S, Nafees S, Hasan SK, Shahid A, Majed F, Sultana S, 2017. Protective effect of Chlorogenic acid against methotrexate induced oxidative stress inflammation and apoptosis in rat liver: An experimental approach. Chemico-Biological Interactions. In press.
- Amabeoku GJ, Eagles P, Scott G, Mayeng I, Springfield E, 2001. Analgesic and antipyretic effects of Dodonaea angustifolia and Salvia africana-lutea. J Ethnopharmacol. 75:117-124.
- Bahadori M, Valizadeh H, Asghari H, Dinparast L, Farimani MM, Bahadori S, 2015. Chemical composition and antimicrobial, cytotoxicity, antioxidant and enzyme inhibitory activities of Salvia spinosa L. Journal of Functional Foods.18:727-736.
- Davis PH. 1982. Flora of Turkey and the east aegean Islands. Edinburgh at the University press. Book, 7, 1982, pp. 431-432.
- Farimani MM, Mohammadi MA, Esmaeili, MA, Salehi P, Ebrahimi NJ, Sonboli A, Hamburger M, 2015. Seco-ursane-type Triterpenoids from Salvia urmiensis with Apoptosis-inducing Activity. Plant Med. 81:1290-1295.
- Feng R, Lu Y, Bowman LL, Qian Y, Castranova V, Ding M, 2005. Inhibition of Activator Protein-1, NF-κB, and MAPKs and Induction of Phase 2 Detoxifying Enzyme Activity by Chlorogenic Acid. J Biol Chem. 280: 27888-27895.
- Giacomelli E, Bertrand S, Nievergelt A, Zwick V, Simoes-Pires C, Marcourt L, Rivara-Minten E, Cuendet M, Bisio A, Wolfender JL, 2013. Cancer chemopreventive diterpenes from Salvia corrugata. Phytochemistry. 96: 257-264
- Gong Y, Li Y, Lu Y, Li L, Abdolmaleky H, Blackburn GL, Zhou JR, 2011. Bioactive tanshinones in Salvia miltiorrhiza inhibit the growth of prostate cancer cells in vitro and in mice. Int J Cancer. 29:1042-1052.
- Granado-Serrano AB, Martín AM, Izquierdo-Pulido M, Goya L, Bravo L, Ramos S, 2007. Molecular mechanisms of (-)-epicatechin and chlorogenic acid on the regulation of the apoptotic and survival/proliferation pathways in a human hepatoma cell line. J Agric Food Chem. 55:2020-2027.
- Johnstone RW, Ruefli AA, Lowe SW, 2002. Apoptosis: A Link between Cancer Genetics and Chemotherapy. Cell 108:153–164.
- Jung HJ, Song YS, Lim CJ, Park EH 2009. Anti-inflammatory, anti-angiogenic and anti-nociceptive activities of an ethanol extract of Salvia plebeia R. Brown. J Ethnopharmacol. 126:355-360.
- Kelen M, Tepe B 2008. Chemical composition, antioxidant and antimicrobial properties of the essential oils of three Salvia species from Turkish flora. Bioresour Technol. 99:4096-4104.
- Kerr JFR, Winterfold CM 1994. Apoptosis its signifcance in Cancer and Cancer Therapy. Cancer. 73:2013-2026.
- Koşar M, Göger F, Başer KHC, 2011. In vitro antioxidant properties and phenolic composition of Salvia halophila Hedge from Turkey. Food Chem. 129: 374-379.
- Lu Y, Yeap FL 2002. Polyphenolics of Salvia – a review. Phytochem. 59:117-140.
- Mei ZY, Shen JZ, Wang Y, Lu AX, Ho WS 2016. Anti-oxidant and anti-cancer activities of Angelica dahurica extract via induction of apoptosis in colon cancer cells. Phytomedicine. 23:1267-1274.
- Morote J, Maldonado X, Morales-Bárrera R, and on behalf of the multidisciplinary group for the study and management of prostate cancer Vall d’Hebron 2016. Prostate cancer. Med Clin.146:121–127.
- Orhan IE, Senol FS, Ozturk N, Akaydin G, Sener B 2012. Profiling of in vitro neurobiological effects and phenolic acids of selected endemic Salvia species. Food Chemistry. 132:1360-1367.
- Prasad NR, Karthikeyan A, Karthikeyan S, Reddy BV 2011. Inhibitory effect of caffeic acid on cancer cell proliferation by oxidative mechanism in human HT-1080 fibrosarcoma cell line. Mol Cell Biochem. 349:11-19.
- Ren Y, Yu J, Douglas Kinghorn A 2016. Development of Anticancer Agents from Plant-Derived Sesquiterpene Lactones. Cur Med Chem, 23: 2397-2420.
- Russo A, Formisano C, Rigano D, Senatore F, Delfine S, Cardile V, Rosselli S, Bruno M 2013. Chemical composition and anticancer activity of essential oils of Mediterranean sage (Salvia officinalis L.) grown in different environmental conditions. Food Chem Toxicol. 55: 42–47.
- Russo A, Formisano C, Riganob D, Cardile V, Arnoldd NA, Senatore F 2016. Comparative phytochemical profile and antiproliferative activity onhuman melanoma cells of essential oils of three lebanese Salvia species. Ind Crops Prod. 83:492-499.
- Sghaier MB, Ismail MB, Bouhlel I, Ghedirac K, Chekir-Ghedira L 2016. Leaf extracts from Teucrium ramosissimum protect against DNA damage in human lymphoblast cell K562 and enhance antioxidant, antigenotoxic and antiproliferative activity. Environ Toxicol Pharmaco. 44: 44–52
- Sokmen A, Jones BM, Erturk M, 1999. The in vitro antibacterial activity of Turkish medicinal plants. J Ethnopharmacol. 67: 79–86
- Tel G, Öztürk M, Duru ME, Harmandar M, Topçu G, 2010. Chemical composition of the essential oil and hexane extract of Salvia chionantha and their antioxidant and anticholinesterase activities. Food Chem Toxicol, 48: 3189-3193.
- Tepe B, Daferera D, Sokmen A, Sokmen M, Polissiou M, 2005. Antimicrobial and antioxidant activities of the essential oil and various extracts of Salvia tomentosa
- Miller (Lamiaceae). Food chem. 90: 333-340. Unnati S, Ripal S, Acharya S, Acharya N 2013. Novel anticancer agents from plant sources. Chinese J Nat Medicin.11:16–23.
- Walker JB, Sytsma KJ, Treutlein J, Wink M 2004. Salvia (Lamiaceae) is not monophyletic: implications for the systematics, radiation, and ecological specializations of Salvia and tribe Mentheae. Am J Bot. 91: 1115-1125.
- Weidner C, Rousseau M, Plauth A, Wowro SJ, Fischer C, Abdel-Aziz H, Sauer S 2015. Melissa officinalis extract induces apoptosis and inhibits proliferation in colon cancer cells through formation of reactive oxygen species. Phytomedicine. 22: 262-270.
- Wu JG, Ma L, Lin SH, Wu YB, Yi J, Yang, BJ, Wu JZ, Wong K H 2017. Anticancer and anti-angiogenic activities of extract from Actinidia eriantha Benth root. J Ethnopharmacol. 203: 1-10.
- Yang LL., Lee CY, Yen KY 2000. Induction of apoptosis by hydrolyzable tannin from Eugenia jambos L. on human leukemia cells. Cancer Lett.157: 65-75
- Yumrutas O, Sokmen A, Akpulat HA, Ozturk N, Daferera D, Sokmen M, Tepe B 2012. Phenolic acid contents, essential oil compositions and antioxidant activities of two varieties of Salvia euphratica from Turkey. Nat Prod Res. 26:1848-1851.
- Zhao Q, Huo XC, Sun FD, Dong RQ 2015. Polyphenol-rich extract of Salvia chinensis exhibits anticancer activity in different cancer cell lines, and induces cell cycle arrest at the G0/G1-phase, apoptosis and loss of mitochondrial membrane potential in pancreatic cancer cells. Mol Med Rep. 12:4843-4850.
Prostat Kanser Hücre Hattı DU145 Üzerine Salvia Pilifera Ekstraktları ile Sentetik Klorojenik ve Kafeik Asidin Sitotoksik ve Apoptotik Etkilerinin Incelenmesi
Öz
Salvia türleri tıbbi etkilerinden dolayı pek çok hastalığın tedavisinde
kullanılmaktadır, Ancak bu türlerin prostat kanseri üzerine etkilerini gösteren
çalışmaların sayısı sınırldır. Bu çalışmada, S. pilifera diklorometan (DCM) ve metanol (MeOH) ekstraktları ile
sentetik klorojenik (CGA) ve kafeik asitin (CA)
DU145 prostat kanser hücreleri üzerine antikanser aktivitelerinin
belirlenmesi amaçlanmıştır. DU145 hücrelerinin canlılığı MTT boyama testi ile
belirlenmiştir. Apoptozun indüklenmesi Annexine V ve 7ADD boyama kiti
kullanılarak belirlenmiştir. Özüt uygulaması sonrasında hücrelerin DNA’ları
izole edilerek fragmentasyona bakılmıştır. Son olarak, BAX, Kaspaz3 ve 9, BcL2
ve BcL-xL gen ekspresyon seviyeleri ölçülmüştür. Bununla birlikte, MeOH
ektraktındaki olası fenolik bileşikler HPLC ile belirlenmiştir. MTT testinde,
ekstrakt ve sentetik fenoliklerin DU145 hücrelerinin canlılığını azalttığı
tespit edilmiştir. Ancak apoptoz indükleme testinde ekstrakt ve fenoliklerin
herhangi bir aktivite sergilemedikleri belirlenmiştir. DNA fragmentasyon
testinde, kontrolle kıyaslandığında ekstrakt uygulanan gruplarda bir farklılık
görülmezken, CGA ve CA uygulama gruplarında sürüntü şeklinde parçalanma
gözlenmiştir. Ayrıca, apoptotik ve antiapoptotik gen ekspresyonlarında zayıf
değişimler gözlenmekle birlikte bu değişimler istatistiksel olarak önemli
bulunmamıştır. Ayrıca, S. pilifera’da
fumarik asit, gallik asit, gallokateşin, kateşin, oleorufein, 4-hidroksibenzoik
asit, kafeik asit, sirinjik asit, ellajik asit, 3-hidroksi sinnamik asit ve
protokateşik asit belirlenmiştir. Sonuç olarak, S. pilifera DCM ve MeOH özütleri ve kullanılan sentetik fenolik
asitlerin prostat kanser hücreleri üzerine belirli dozlarda (DCM için ≥50 µg ml-1; MeOH
için ≥ 100 µg ml-1; CGA and
CA için ≥ 1 µg ml-1)
sitotoksit etki gösterdikleri, ancak bu etkinin apoptoz yolağıyla ilişkili
olmadığı belirlenmiştir.
Anahtar Kelimeler
S. pilifera ekstrakt Kafeik asit Klorojenik asit Apoptosis Prostat kanser
Kaynakça
- Ali N, Rashid S, Nafees S, Hasan SK, Shahid A, Majed F, Sultana S, 2017. Protective effect of Chlorogenic acid against methotrexate induced oxidative stress inflammation and apoptosis in rat liver: An experimental approach. Chemico-Biological Interactions. In press.
- Amabeoku GJ, Eagles P, Scott G, Mayeng I, Springfield E, 2001. Analgesic and antipyretic effects of Dodonaea angustifolia and Salvia africana-lutea. J Ethnopharmacol. 75:117-124.
- Bahadori M, Valizadeh H, Asghari H, Dinparast L, Farimani MM, Bahadori S, 2015. Chemical composition and antimicrobial, cytotoxicity, antioxidant and enzyme inhibitory activities of Salvia spinosa L. Journal of Functional Foods.18:727-736.
- Davis PH. 1982. Flora of Turkey and the east aegean Islands. Edinburgh at the University press. Book, 7, 1982, pp. 431-432.
- Farimani MM, Mohammadi MA, Esmaeili, MA, Salehi P, Ebrahimi NJ, Sonboli A, Hamburger M, 2015. Seco-ursane-type Triterpenoids from Salvia urmiensis with Apoptosis-inducing Activity. Plant Med. 81:1290-1295.
- Feng R, Lu Y, Bowman LL, Qian Y, Castranova V, Ding M, 2005. Inhibition of Activator Protein-1, NF-κB, and MAPKs and Induction of Phase 2 Detoxifying Enzyme Activity by Chlorogenic Acid. J Biol Chem. 280: 27888-27895.
- Giacomelli E, Bertrand S, Nievergelt A, Zwick V, Simoes-Pires C, Marcourt L, Rivara-Minten E, Cuendet M, Bisio A, Wolfender JL, 2013. Cancer chemopreventive diterpenes from Salvia corrugata. Phytochemistry. 96: 257-264
- Gong Y, Li Y, Lu Y, Li L, Abdolmaleky H, Blackburn GL, Zhou JR, 2011. Bioactive tanshinones in Salvia miltiorrhiza inhibit the growth of prostate cancer cells in vitro and in mice. Int J Cancer. 29:1042-1052.
- Granado-Serrano AB, Martín AM, Izquierdo-Pulido M, Goya L, Bravo L, Ramos S, 2007. Molecular mechanisms of (-)-epicatechin and chlorogenic acid on the regulation of the apoptotic and survival/proliferation pathways in a human hepatoma cell line. J Agric Food Chem. 55:2020-2027.
- Johnstone RW, Ruefli AA, Lowe SW, 2002. Apoptosis: A Link between Cancer Genetics and Chemotherapy. Cell 108:153–164.
- Jung HJ, Song YS, Lim CJ, Park EH 2009. Anti-inflammatory, anti-angiogenic and anti-nociceptive activities of an ethanol extract of Salvia plebeia R. Brown. J Ethnopharmacol. 126:355-360.
- Kelen M, Tepe B 2008. Chemical composition, antioxidant and antimicrobial properties of the essential oils of three Salvia species from Turkish flora. Bioresour Technol. 99:4096-4104.
- Kerr JFR, Winterfold CM 1994. Apoptosis its signifcance in Cancer and Cancer Therapy. Cancer. 73:2013-2026.
- Koşar M, Göger F, Başer KHC, 2011. In vitro antioxidant properties and phenolic composition of Salvia halophila Hedge from Turkey. Food Chem. 129: 374-379.
- Lu Y, Yeap FL 2002. Polyphenolics of Salvia – a review. Phytochem. 59:117-140.
- Mei ZY, Shen JZ, Wang Y, Lu AX, Ho WS 2016. Anti-oxidant and anti-cancer activities of Angelica dahurica extract via induction of apoptosis in colon cancer cells. Phytomedicine. 23:1267-1274.
- Morote J, Maldonado X, Morales-Bárrera R, and on behalf of the multidisciplinary group for the study and management of prostate cancer Vall d’Hebron 2016. Prostate cancer. Med Clin.146:121–127.
- Orhan IE, Senol FS, Ozturk N, Akaydin G, Sener B 2012. Profiling of in vitro neurobiological effects and phenolic acids of selected endemic Salvia species. Food Chemistry. 132:1360-1367.
- Prasad NR, Karthikeyan A, Karthikeyan S, Reddy BV 2011. Inhibitory effect of caffeic acid on cancer cell proliferation by oxidative mechanism in human HT-1080 fibrosarcoma cell line. Mol Cell Biochem. 349:11-19.
- Ren Y, Yu J, Douglas Kinghorn A 2016. Development of Anticancer Agents from Plant-Derived Sesquiterpene Lactones. Cur Med Chem, 23: 2397-2420.
- Russo A, Formisano C, Rigano D, Senatore F, Delfine S, Cardile V, Rosselli S, Bruno M 2013. Chemical composition and anticancer activity of essential oils of Mediterranean sage (Salvia officinalis L.) grown in different environmental conditions. Food Chem Toxicol. 55: 42–47.
- Russo A, Formisano C, Riganob D, Cardile V, Arnoldd NA, Senatore F 2016. Comparative phytochemical profile and antiproliferative activity onhuman melanoma cells of essential oils of three lebanese Salvia species. Ind Crops Prod. 83:492-499.
- Sghaier MB, Ismail MB, Bouhlel I, Ghedirac K, Chekir-Ghedira L 2016. Leaf extracts from Teucrium ramosissimum protect against DNA damage in human lymphoblast cell K562 and enhance antioxidant, antigenotoxic and antiproliferative activity. Environ Toxicol Pharmaco. 44: 44–52
- Sokmen A, Jones BM, Erturk M, 1999. The in vitro antibacterial activity of Turkish medicinal plants. J Ethnopharmacol. 67: 79–86
- Tel G, Öztürk M, Duru ME, Harmandar M, Topçu G, 2010. Chemical composition of the essential oil and hexane extract of Salvia chionantha and their antioxidant and anticholinesterase activities. Food Chem Toxicol, 48: 3189-3193.
- Tepe B, Daferera D, Sokmen A, Sokmen M, Polissiou M, 2005. Antimicrobial and antioxidant activities of the essential oil and various extracts of Salvia tomentosa
- Miller (Lamiaceae). Food chem. 90: 333-340. Unnati S, Ripal S, Acharya S, Acharya N 2013. Novel anticancer agents from plant sources. Chinese J Nat Medicin.11:16–23.
- Walker JB, Sytsma KJ, Treutlein J, Wink M 2004. Salvia (Lamiaceae) is not monophyletic: implications for the systematics, radiation, and ecological specializations of Salvia and tribe Mentheae. Am J Bot. 91: 1115-1125.
- Weidner C, Rousseau M, Plauth A, Wowro SJ, Fischer C, Abdel-Aziz H, Sauer S 2015. Melissa officinalis extract induces apoptosis and inhibits proliferation in colon cancer cells through formation of reactive oxygen species. Phytomedicine. 22: 262-270.
- Wu JG, Ma L, Lin SH, Wu YB, Yi J, Yang, BJ, Wu JZ, Wong K H 2017. Anticancer and anti-angiogenic activities of extract from Actinidia eriantha Benth root. J Ethnopharmacol. 203: 1-10.
- Yang LL., Lee CY, Yen KY 2000. Induction of apoptosis by hydrolyzable tannin from Eugenia jambos L. on human leukemia cells. Cancer Lett.157: 65-75
- Yumrutas O, Sokmen A, Akpulat HA, Ozturk N, Daferera D, Sokmen M, Tepe B 2012. Phenolic acid contents, essential oil compositions and antioxidant activities of two varieties of Salvia euphratica from Turkey. Nat Prod Res. 26:1848-1851.
- Zhao Q, Huo XC, Sun FD, Dong RQ 2015. Polyphenol-rich extract of Salvia chinensis exhibits anticancer activity in different cancer cell lines, and induces cell cycle arrest at the G0/G1-phase, apoptosis and loss of mitochondrial membrane potential in pancreatic cancer cells. Mol Med Rep. 12:4843-4850.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Bölüm | ARAŞTIRMA MAKALESİ (Research Article) |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Nisan 2018 |
| Gönderilme Tarihi | 29 Mart 2017 |
| Kabul Tarihi | 22 Mayıs 2007 |
| Yayımlandığı Sayı | Yıl 2018 |
Kaynak Göster
Cited By
Exploring the Antiproliferative Mechanisms of Urtica dioica L. extract in Human Promyelocytic Leukemia Cell Line
Harran Üniversitesi Tıp Fakültesi Dergisi
https://doi.org/10.35440/hutfd.1012538
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