Endometriyal hücrelerde Spirulina platensis ekstresinin kimyasal bileşiminin seçici sitotoksisitesi: İn vitro ve in siliko yaklaşım
Abstract
Mikroalgler, yüksek miktarda biyoaktif bileşik kaynağı olarak kabul edilmektedir. Bu çeşitli kimyasallar, ilaç adaylarına dönüşmek için umut verici bir potansiyele sahiptir. Bu nedenle, bu çalışmanın amacı, Spirulina platensis mikroalg ekstraktının endometriyal kanser hücrelerine karşı potansiyel anti-kanser etkilerini belirlemektir. Ishikawa endometriyal kanser hücre hattı üzerinde S. platensis mikroalg ekstraktının seçici sitotoksik etkisi ve ,sitotoksisite indeksi, DNA fragmantasyonun belirlenmesi ve apoptoz ile ilişkili Bad, Poli-ADP Riboz Polimeraz-1 (PARP1), p53, Akt1 ve kaspaz-3 sinyal proteinlerinin gen ifade seviyelerindeki değişimi belirlenmiştir. ECV304 insan göbek damarı endotel hücresi hücre hattı ise, kontrol hücre hattı olarak kullanılmıştır. 500 μg mL-1 S. platensis mikroalg ekstraktının Ishikawa ve ECV304 hücreleri üzerindeki sitotoksik etkileri sırasıyla % 43±4.87 ve % 22±1.87 olarak belirlenmiştir. Ekstrakttaki spesifik bileşikleri tanımlamak için GC-MS analizi gerçekleştirilmiş ve ekstrede 7 ana bileşiğin bol miktarda mevcut olduğu belirlenmiştir. S. platensis ekstresi tarafından indüklenen DNA fragmantasyonu, GC-MS ile tanımlanan bileşiklerin PARP1 ile etkileşimi ile ilgili olabileceğinden, ek olarak in siliko analiz yapılmıştır. Sonuçlar, apoptotik yanıta katkıda bulunan olası bir PARP1 inhibitör mekanizmasının varlığını göstermiştir Sonuç olarak, S. platensis mikroalg ekstraktında bulunan spesifik bileşen ile endometriyal hücrelerdeki sitotoksisite arasında olası bir bağlantı, in vitro ve in siliko yaklaşımların birleştirilmesiyle oluşturulmuştur. Bu yaklaşımlar sonucu, S. platensis mikroalg ekstraktından bulunan potansiyel anti-kanser bileşen adaylarının tanımlanmasına katkı sağlanmıştır.
Keywords
apoptoz, endometriyal kanser hücreleri, GC-MS, mikroalg, sitotoksisite
References
- Arslan BA, Isik FB, Gur H, Ozen F, Catal, T 2017. Apoptotic Effect Of Nigella sativa On Human Lymphoma U937 Cells. Pharmacognosy Magazine 13(3): 628-632.
- Atasever-Arslan B, Yilancioglu K, Bekaroglu MG, Taskin E, Altinoz E, Cetiner S 2015. Cytotoxic Effect Of Extract From Dunaliella salina Against SH-SY5Y Neuroblastoma Cells. General Physiology and Biophysics 34(2): 201-207.
- Atasever-Arslan B, Yilancioglu K, Kalkan Z, Timucin AC, Gür H, Isik FB, Deniz E, Erman B, Cetiner S 2016. Screening Of New Antileukemic Agents From Essential Oils Of Algae Extracts And Computational Modeling Of Their İnteractions With İntracellular Signaling Nodes. European Journal of Pharmaceutical Sciences 83: 120-131.
- Atasever-Arslan B, Yilancioglu K, Kuşoğlu-Gültekin S, Albayrak İG 2022. Chemical Constituent Of Isochrysis galbana Microalgae Extract And Its Cytotoxic Activities On Leukemic Cell Lines. İstanbul Journal of Pharmacy 52(1): 64-68.
- Brooks BR, Brooks CL, Mackerell AD, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A, Caves L, Cui Q, Dinner AR, Feig M, Fischer S, Gao J, Hodoscek M, Im W, Kuczera K, Lazaridis T, Ma J, Ovchinnikov V, Paci E, Pastor RW, Post CB, Pu JZ, Schaefer M, Tidor B, Venable RM, Woodcock HL, Wu X, Yang W, York DM, Karplus M 2009. CHARMM: The Biomolecular Simulation Program. Journal of Computational Chemistry 30: 1545-1614.
- Del Carmen M, Boruta D, Schorge J 2011. Recurrent Endometrial Cancer. Clinical Obstetrics and Gynecology 54(2): 266-277.
- Feig M, MacKerell AD, Brooks CL 2003. Force Field İnfluence on The Observation of Π-Helical Protein Structures İn Molecular Dynamics Simulations. The Journal of Physical Chemistry B 107: 2831-2836.
- Hevir-Kene N, Rizner TL 2015. The Endometrial Cancer Cell Lines Ishikawa And HEC-1A, And The Control Cell Line HIEEC, Differ İn Expression Of Estrogen Biosynthetic And Metabolic Genes, And İn Androstenedione And Estrone-Sulfate Metabolism. Chemico-Biological Interactions 234: 309-319.
- Humphrey W, Dalke A, Schulten K 1996. VMD: Visual Molecular Dynamics. Journal of Molecular Graphics and Modelling 14: 33-38, 27-38.
- Iwashita A, Hattori K, Yamamoto H, Ishida J, Kido Y, Kamijo K, Murano K, Miyake H, Kinoshita T, Warizaya M, Ohkubo M, Matsuoka N, Mutoh, S 2005. Discovery Of Quinazolinone And Quinoxaline Derivatives As Potent And Selective Poly(ADP-Ribose) Polymerase-1/2 İnhibitors. FEBS Letters 579: 1389-1393.
- Jorgensen WL, Madura JD 1983. Quantum And Statistical Mechanical Studies Of Liquids. 25. Solvation And Conformation Of Methanol İn Water. Journal of the American Chemical Society 105: 1407-1413.
- Karthikeyan SC, Velmurugan S, Donio MB, Michaelbabu M, Citarasu T 2014. Studies On The Antimicrobial Potential And Structural Characterization Of Fatty Acids Extracted From Sydney Rock Oyster Saccostrea glomerata. Annals of Clinical Microbiology and Antimicrobials 13: 332.
- Kaya B, Atasever-Arslan B, Kalkan Z, Gur H, Ulkuseven B 2016. Apoptotic Mechanisms Of N1-Acetylacetone, N4-4-Methoxy-Salicylidene-Thiosemicarbazide Chelating With Nickel(II) On HL60 Leukemia Cells. General Physiology and Biophysics 35(4): 451-458.
- Khan AA, Alanazi AM, Jabeen, M, Chauhan A, Abdelhameed AS 2013. Design, Synthesis And İn Vitro Anticancer Evaluation Of A Stearic Acid-Based Ester Conjugate. Anticancer Research 33: 2517-2524.
- Kok YY, Chu WL, Phang SM, Mohamed SM, Naidu R, Lai PJ, Ling SN, Mak JW, Lim PKC, Balraj P, Khoo ASB 2011. Inhibitory Activities Of Microalgal Extracts Against Epstein-Barr Virus DNA Release From Lymphoblastoid Cells. Journal of Zhejiang University Science 12: 335-345.
- Konickova R, Vankova K, Vanikova J, Vánová V, Muchová L, Subhanová I, Zadinová M, Zelenka J, Dvořák A, Kolář M, Strnad H, Rimpelová S, Ruml T, Wong RJ, Vítek L 2014. Anti-Cancer Effects Of Blue-Green Alga Spirulina platensis, A Natural Source Of Bilirubin-Like Tetrapyrrolic Compounds. Annals of Hepatology 13: 273-283.
- Koru E, Cirik S 2003. The effects of temperature on growth and some biochemical characteristics of microalgae Spirulina platensis (Cyanophyceae). E.U. Journal of Fisheries & Aquatic Sciences 20(3-4): 419 – 422.
- Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG, Earnshaw WC 1994. Cleavage Of Poly(ADP-Ribose) Polymerase By A Proteinase With Properties Like ICE. Nature 371: 346-347.
- MacKerell AD, Bashford D, Bellott M, Dunbrack RL, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher WE, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiórkiewicz-Kuczera J, Yin D, Karplus M 1998. All-Atom Empirical Potential For Molecular Modeling And Dynamics Studies Of Proteins. The Journal of Physical Chemistry B 102: 3586-3616.
- MacKerell AD, Feig M, Brooks CL 2004. Improved Treatment Of The Protein Backbone İn Empirical Force Fields. Journal of the American Chemical Society 126: 698-699.
- Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, Munday NA, Raju SM, Smulson ME, Yamin T, Yu VL, Miller DK 1995. Identification And Inhibition Of The ICE/CED-3 Protease Necessary For Mammalian Apoptosis. Nature 376: 37-43.
- Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E. Villa E, Chipot C, Skeel RD, Kalé, L, Schulten K 2005. Scalable Molecular Dynamics With NAMD. Journal of Computational Chemistry 26: 1781-1802.
- Pirildar S, Sutlupinar N, Atasever B, Erdem-Kuruca S, Papouskova B, Šimánek, V 2010. Chemical Constituents Of The Different Parts Of Colchicum Baytopiorum And Their Cytotoxic Activities On K562 And HL60 Cell Lines. Pharmaceutical Biology 48: 32-39.
- Russo A, Cardile V, Graziano AC, Formisano C, Rigano D, Canzoneri M, Bruno M, Senatore F 2015. Comparison Of Essential Oil Components And İn Vitro Anticancer Activity İn Wild And Cultivated Salvia verbenaca. Natural Product Research 29: 1630-1640.
- Saini MK, Sanyal, SN 2014. Piroxicam And C-Phycocyanin Prevent Colon Carcinogenesis By İnhibition Of Membrane Fluidity And Canonical Wnt/Beta-Catenin Signaling While Up-Regulating Ligand Dependent Transcription Factor PPARgamma. Biomedicine & Pharmacotherapy 68: 537-550.
- Suda K, Rothen-Rutishauser B, Gunthert M, Wunderli-Allenspach H 2011. Phenotypic Characterization Of Human Umbilical Vein Endothelial (ECV304) And Urinary Carcinoma (T24) Cells: Endothelial Versus Epithelial Features. In Vitro Cellular & Developmental Biology 37: 505-514.
- Takeara R, Jimenez PC, Wilke DV, Moraes MO, Pessoa C, Lopes NP, Lopes JLC, Lotufo TMC, Costa-Lotufo LV 2008. Antileukemic Effects Of Didemnum psammatodes (Tunicata: Ascidiacea) Constituents. Comparative Biochemistry And Physiology - Part A 151: 363-369.
- Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S, Zhong S, Shim J, Darian E, Guvench O, Lopes P, Vorobyov I, Mackerell AD 2010. CHARMM General Force Field: A Force Field For Drug-Like Molecules Compatible With The CHARMM All-Atom Additive Biological Force Fields. Journal of Computational Chemistry 31: 671-690.
- Vanommeslaeghe K, Raman EP, MacKerell AD 2012. Automation Of The CHARMM General Force Field (CGenFF) II: Assignment Of Bonded Parameters And Partial Atomic Charges. Journal of Chemical Information and Modeling, 52: 3155-3168.
- Vanommeslaeghe, K, MacKerell AD, 2012. Automation Of The CHARMM General Force Field (CGenFF) I: Bond Perception And Atom Typing. Journal of Chemical Information and Modeling 52: 3144-3154.
- West JD, Ji C, Marnett LJ 2005. Modulation of DNA Fragmentation Factor 40 Nuclease Activity By Poly(ADP-ribose) Polymerase-1. Journal of Biological Chemistry 280: 15141-15147, (2005).
- Wei LS, Wee W, Siong JY, Syamsumir DF 2011. Characterization Of Anticancer, Antimicrobial, Antioxidant Properties And Chemical Compositions Of Peperomia pellucida Leaf Extract. Acta Medica Iranica 49: 670-674.
- Wong SK, Lim YY, Ling SK, Chan EWC 2014. Antiproliferative Activity Of Vallaris glabra Kuntze (Apocynaceae). Pharmacognosy Magazine 10: 232-239.
- Yu W, He X, Vanommeslaeghe K, MacKerell AD 2012. Extension Of The CHARMM General Force Field To Sulfonyl-containing Compounds And Its Utility In Biomolecular Simulations. Journal of Computational Chemistry 33: 2451-2468.
- Zhang S, Gong TT, Liu FH, Jiang YT, Sun H, Ma XX, Zhao YH, Wu QJ 2019. Global, Regional, and National Burden of Endometrial Cancer, 1990–2017: Results From the Global Burden of Disease Study, 2017. Frontiers in Oncology 9: 1440-1452.
Selective cytotoxicity of chemical composition of Spirulina platensis extract in endometrial cells: In vitro and in silico approach
Abstract
Microalgae are considered as an ample source of bioactive compounds. These wide variety of chemicals possess promising potential to translate into drug candidates. Hence, the aim of this study is to determine potential anti-cancer effects of Spirulina platensis microalgae extract against endometrial cancer cells. The selective cytotoxic effect and cytotoxicity index of S. platensis microalgae extract on the Ishikawa endometrial cancer cell line, the determination of DNA fragmentation and the change in gene expression levels of apoptosis-related Bad, Poly-ADP Ribose Polymerase-1 (PARP1), p53, Akt1 and caspase-3 signaling proteins were determined. ECV304 human umbilical vein endothelial cell line was used for a control cell line. Cytotoxic effects of 500 μg mL-1 of S. platensis microalgae extract on Ishikawa and ECV304 cells were determined as 43±4.87 % and 22±1.87 % respectively. In order to delineate specific compounds in the extract, GC-MS analysis was further conducted and seven major compounds revealed to be abundantly present. Since DNA fragmentation induced by S.platensis extract might be related interaction of GC-MS identified compounds with PARP1, an in silico analysis was further implemented. Results indicated the presence of a possible PARP1 inhibitory mechanism contributing to the apoptotic response. In conclusion, a possible link between a specific compound found in S. platensis microalgae extract and the cytotoxicity in endometrial cells was formed through combining in vitro and in silico approaches. The result of these approaches has contributed to the identification of potential anti-cancer compound candidates found in S. platensis microalgae extract.
Keywords
Apoptosis, endometrial cancer cells, GC-MS, microalgae, cytotoxicity
References
- Arslan BA, Isik FB, Gur H, Ozen F, Catal, T 2017. Apoptotic Effect Of Nigella sativa On Human Lymphoma U937 Cells. Pharmacognosy Magazine 13(3): 628-632.
- Atasever-Arslan B, Yilancioglu K, Bekaroglu MG, Taskin E, Altinoz E, Cetiner S 2015. Cytotoxic Effect Of Extract From Dunaliella salina Against SH-SY5Y Neuroblastoma Cells. General Physiology and Biophysics 34(2): 201-207.
- Atasever-Arslan B, Yilancioglu K, Kalkan Z, Timucin AC, Gür H, Isik FB, Deniz E, Erman B, Cetiner S 2016. Screening Of New Antileukemic Agents From Essential Oils Of Algae Extracts And Computational Modeling Of Their İnteractions With İntracellular Signaling Nodes. European Journal of Pharmaceutical Sciences 83: 120-131.
- Atasever-Arslan B, Yilancioglu K, Kuşoğlu-Gültekin S, Albayrak İG 2022. Chemical Constituent Of Isochrysis galbana Microalgae Extract And Its Cytotoxic Activities On Leukemic Cell Lines. İstanbul Journal of Pharmacy 52(1): 64-68.
- Brooks BR, Brooks CL, Mackerell AD, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A, Caves L, Cui Q, Dinner AR, Feig M, Fischer S, Gao J, Hodoscek M, Im W, Kuczera K, Lazaridis T, Ma J, Ovchinnikov V, Paci E, Pastor RW, Post CB, Pu JZ, Schaefer M, Tidor B, Venable RM, Woodcock HL, Wu X, Yang W, York DM, Karplus M 2009. CHARMM: The Biomolecular Simulation Program. Journal of Computational Chemistry 30: 1545-1614.
- Del Carmen M, Boruta D, Schorge J 2011. Recurrent Endometrial Cancer. Clinical Obstetrics and Gynecology 54(2): 266-277.
- Feig M, MacKerell AD, Brooks CL 2003. Force Field İnfluence on The Observation of Π-Helical Protein Structures İn Molecular Dynamics Simulations. The Journal of Physical Chemistry B 107: 2831-2836.
- Hevir-Kene N, Rizner TL 2015. The Endometrial Cancer Cell Lines Ishikawa And HEC-1A, And The Control Cell Line HIEEC, Differ İn Expression Of Estrogen Biosynthetic And Metabolic Genes, And İn Androstenedione And Estrone-Sulfate Metabolism. Chemico-Biological Interactions 234: 309-319.
- Humphrey W, Dalke A, Schulten K 1996. VMD: Visual Molecular Dynamics. Journal of Molecular Graphics and Modelling 14: 33-38, 27-38.
- Iwashita A, Hattori K, Yamamoto H, Ishida J, Kido Y, Kamijo K, Murano K, Miyake H, Kinoshita T, Warizaya M, Ohkubo M, Matsuoka N, Mutoh, S 2005. Discovery Of Quinazolinone And Quinoxaline Derivatives As Potent And Selective Poly(ADP-Ribose) Polymerase-1/2 İnhibitors. FEBS Letters 579: 1389-1393.
- Jorgensen WL, Madura JD 1983. Quantum And Statistical Mechanical Studies Of Liquids. 25. Solvation And Conformation Of Methanol İn Water. Journal of the American Chemical Society 105: 1407-1413.
- Karthikeyan SC, Velmurugan S, Donio MB, Michaelbabu M, Citarasu T 2014. Studies On The Antimicrobial Potential And Structural Characterization Of Fatty Acids Extracted From Sydney Rock Oyster Saccostrea glomerata. Annals of Clinical Microbiology and Antimicrobials 13: 332.
- Kaya B, Atasever-Arslan B, Kalkan Z, Gur H, Ulkuseven B 2016. Apoptotic Mechanisms Of N1-Acetylacetone, N4-4-Methoxy-Salicylidene-Thiosemicarbazide Chelating With Nickel(II) On HL60 Leukemia Cells. General Physiology and Biophysics 35(4): 451-458.
- Khan AA, Alanazi AM, Jabeen, M, Chauhan A, Abdelhameed AS 2013. Design, Synthesis And İn Vitro Anticancer Evaluation Of A Stearic Acid-Based Ester Conjugate. Anticancer Research 33: 2517-2524.
- Kok YY, Chu WL, Phang SM, Mohamed SM, Naidu R, Lai PJ, Ling SN, Mak JW, Lim PKC, Balraj P, Khoo ASB 2011. Inhibitory Activities Of Microalgal Extracts Against Epstein-Barr Virus DNA Release From Lymphoblastoid Cells. Journal of Zhejiang University Science 12: 335-345.
- Konickova R, Vankova K, Vanikova J, Vánová V, Muchová L, Subhanová I, Zadinová M, Zelenka J, Dvořák A, Kolář M, Strnad H, Rimpelová S, Ruml T, Wong RJ, Vítek L 2014. Anti-Cancer Effects Of Blue-Green Alga Spirulina platensis, A Natural Source Of Bilirubin-Like Tetrapyrrolic Compounds. Annals of Hepatology 13: 273-283.
- Koru E, Cirik S 2003. The effects of temperature on growth and some biochemical characteristics of microalgae Spirulina platensis (Cyanophyceae). E.U. Journal of Fisheries & Aquatic Sciences 20(3-4): 419 – 422.
- Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG, Earnshaw WC 1994. Cleavage Of Poly(ADP-Ribose) Polymerase By A Proteinase With Properties Like ICE. Nature 371: 346-347.
- MacKerell AD, Bashford D, Bellott M, Dunbrack RL, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher WE, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiórkiewicz-Kuczera J, Yin D, Karplus M 1998. All-Atom Empirical Potential For Molecular Modeling And Dynamics Studies Of Proteins. The Journal of Physical Chemistry B 102: 3586-3616.
- MacKerell AD, Feig M, Brooks CL 2004. Improved Treatment Of The Protein Backbone İn Empirical Force Fields. Journal of the American Chemical Society 126: 698-699.
- Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, Munday NA, Raju SM, Smulson ME, Yamin T, Yu VL, Miller DK 1995. Identification And Inhibition Of The ICE/CED-3 Protease Necessary For Mammalian Apoptosis. Nature 376: 37-43.
- Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E. Villa E, Chipot C, Skeel RD, Kalé, L, Schulten K 2005. Scalable Molecular Dynamics With NAMD. Journal of Computational Chemistry 26: 1781-1802.
- Pirildar S, Sutlupinar N, Atasever B, Erdem-Kuruca S, Papouskova B, Šimánek, V 2010. Chemical Constituents Of The Different Parts Of Colchicum Baytopiorum And Their Cytotoxic Activities On K562 And HL60 Cell Lines. Pharmaceutical Biology 48: 32-39.
- Russo A, Cardile V, Graziano AC, Formisano C, Rigano D, Canzoneri M, Bruno M, Senatore F 2015. Comparison Of Essential Oil Components And İn Vitro Anticancer Activity İn Wild And Cultivated Salvia verbenaca. Natural Product Research 29: 1630-1640.
- Saini MK, Sanyal, SN 2014. Piroxicam And C-Phycocyanin Prevent Colon Carcinogenesis By İnhibition Of Membrane Fluidity And Canonical Wnt/Beta-Catenin Signaling While Up-Regulating Ligand Dependent Transcription Factor PPARgamma. Biomedicine & Pharmacotherapy 68: 537-550.
- Suda K, Rothen-Rutishauser B, Gunthert M, Wunderli-Allenspach H 2011. Phenotypic Characterization Of Human Umbilical Vein Endothelial (ECV304) And Urinary Carcinoma (T24) Cells: Endothelial Versus Epithelial Features. In Vitro Cellular & Developmental Biology 37: 505-514.
- Takeara R, Jimenez PC, Wilke DV, Moraes MO, Pessoa C, Lopes NP, Lopes JLC, Lotufo TMC, Costa-Lotufo LV 2008. Antileukemic Effects Of Didemnum psammatodes (Tunicata: Ascidiacea) Constituents. Comparative Biochemistry And Physiology - Part A 151: 363-369.
- Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S, Zhong S, Shim J, Darian E, Guvench O, Lopes P, Vorobyov I, Mackerell AD 2010. CHARMM General Force Field: A Force Field For Drug-Like Molecules Compatible With The CHARMM All-Atom Additive Biological Force Fields. Journal of Computational Chemistry 31: 671-690.
- Vanommeslaeghe K, Raman EP, MacKerell AD 2012. Automation Of The CHARMM General Force Field (CGenFF) II: Assignment Of Bonded Parameters And Partial Atomic Charges. Journal of Chemical Information and Modeling, 52: 3155-3168.
- Vanommeslaeghe, K, MacKerell AD, 2012. Automation Of The CHARMM General Force Field (CGenFF) I: Bond Perception And Atom Typing. Journal of Chemical Information and Modeling 52: 3144-3154.
- West JD, Ji C, Marnett LJ 2005. Modulation of DNA Fragmentation Factor 40 Nuclease Activity By Poly(ADP-ribose) Polymerase-1. Journal of Biological Chemistry 280: 15141-15147, (2005).
- Wei LS, Wee W, Siong JY, Syamsumir DF 2011. Characterization Of Anticancer, Antimicrobial, Antioxidant Properties And Chemical Compositions Of Peperomia pellucida Leaf Extract. Acta Medica Iranica 49: 670-674.
- Wong SK, Lim YY, Ling SK, Chan EWC 2014. Antiproliferative Activity Of Vallaris glabra Kuntze (Apocynaceae). Pharmacognosy Magazine 10: 232-239.
- Yu W, He X, Vanommeslaeghe K, MacKerell AD 2012. Extension Of The CHARMM General Force Field To Sulfonyl-containing Compounds And Its Utility In Biomolecular Simulations. Journal of Computational Chemistry 33: 2451-2468.
- Zhang S, Gong TT, Liu FH, Jiang YT, Sun H, Ma XX, Zhao YH, Wu QJ 2019. Global, Regional, and National Burden of Endometrial Cancer, 1990–2017: Results From the Global Burden of Disease Study, 2017. Frontiers in Oncology 9: 1440-1452.
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