Induction of apoptosis in cancer cell lines by the Red Sea brine pool bacterial extracts

BMC Complementary and Alternative Medicine

Volumn 13, Issue , 2013, Pages

  Sagar, Sunil ^a   Esau, Luke ^a   Holtermann, Karie ^a   Hikmawan, Tyas ^a   Zhang, Guishan ^a   Stingl, Ulrich ^a   Bajic, Vladimir B ^a   Kaur, Mandeep ^a  

^a KING ABDULLAH UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Saudi Arabia)

Author keywords

Apoptosis; Cancer; Deep sea brine pools; Marine bacteria; Natural products

Indexed keywords

CASPASE 3; CASPASE 7; CASPASE 8; CASPASE 9; HISTONE H2AX; NATURAL PRODUCT; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; PHOSPHATIDYLSERINE;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BACTERIAL STRAIN; BACTERIUM; BIOASSAY; CANCER CELL CULTURE; CELL DEATH; CELL STRAIN DU 145; CELL STRAIN MCF 7; CHROMOHALOBACTER ISRAELENSIS; CHROMOHALOBACTER SALEXIGENS; DEEP SEA; DOWNSTREAM PROCESSING; HALOMONAS MERIDIANA; HELA CELL; HUMAN; HUMAN CELL; IDIOMARINA LOIHIENSIS; IN VITRO STUDY; MARINE ENVIRONMENT; MITOCHONDRIAL MEMBRANE POTENTIAL; NONHUMAN; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; WESTERN BLOTTING;

ANTINEOPLASTIC AGENTS; APOPTOSIS; AQUATIC ORGANISMS; BIOLOGICAL PRODUCTS; CASPASES; CELL LINE, TUMOR; CELL PROLIFERATION; FLOW CYTOMETRY; HALOMONADACEAE; HISTONES; HUMANS; INDIAN OCEAN; MEMBRANE POTENTIAL, MITOCHONDRIAL; POLY(ADP-RIBOSE) POLYMERASES; WATER MICROBIOLOGY;

EID: 84889035403     PISSN: None     EISSN: 14726882     Source Type: Journal    
DOI: 10.1186/1472-6882-13-344     Document Type: Article

References (82)

1. Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012, 75:311-335. 10.1021/np200906s, 3721181, 22316239.
2. Kinghorn AD, Chin YW, Swanson SM. Discovery of natural product anticancer agents from biodiverse organisms. Curr Opin Drug Discov Devel 2009, 12:189-196. 2877274, 19333864.
3. Laatsch H. AntiBase, a Database for rapid dereplication and structure determination of microbial natural products. Book AntiBase, a Database for rapid dereplication and structure determination of microbial natural products 2010, Weinheim, Germany: Wiley-VCH, Editor ed.^eds.
4. Newman DJ, Cragg GM. Marine natural products and related compounds in clinical and advanced preclinical trials. J Nat Prod 2004, 67:1216-1238. 10.1021/np040031y, 15332835.
5. Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod 2007, 70:461-477. 10.1021/np068054v, 17309302.
6. Tan LT. Bioactive natural products from marine cyanobacteria for drug discovery. Phytochemistry 2007, 68:954-979. 10.1016/j.phytochem.2007.01.012, 17336349.
7. Fenical W, Jensen PR, Palladino MA, Lam KS, Lloyd GK, Potts BC. Discovery and development of the anticancer agent salinosporamide A (NPI-0052). Bioorg Med Chem 2009, 17:2175-2180. 10.1016/j.bmc.2008.10.075, 2814440, 19022674.
8. Gulder TA, Moore BS. Chasing the treasures of the sea - bacterial marine natural products. Curr Opin Microbiol 2009, 12:252-260. 10.1016/j.mib.2009.05.002, 2695832, 19481972.
9. Skropeta D. Deep-sea natural products. Nat Prod Rep 2008, 25:1131-1166. 10.1039/b808743a, 19030606.
10. Russo P, Nastrucci C, Cesario A. From the sea to anticancer therapy. Curr Med Chem 2011, 18:3551-3562. 10.2174/092986711796642652, 21756228.
11. Thornburg CC, Zabriskie TM, McPhail KL. Deep-sea hydrothermal vents: potential hot spots for natural products discovery?. J Nat Prod 2010, 73:489-499. 10.1021/np900662k, 20099811.
12. Kameyama T, Takahashi A, Kurasawa S, Ishizuka M, Okami Y, Takeuchi T, Umezawa H. Bisucaberin, a new siderophore, sensitizing tumor cells to macrophage-mediated cytolysis. I. Taxonomy of the producing organism, isolation and biological properties. J Antibiot (Tokyo) 1987, 40:1664-1670. 10.7164/antibiotics.40.1664, 2962972.
13. Homann VV, Sandy M, Tincu JA, Templeton AS, Tebo BM, Butler A. Loihichelins A-F, a suite of amphiphilic siderophores produced by the marine bacterium Halomonas LOB-5. J Nat Prod 2009, 72:884-888. 10.1021/np800640h, 2891265, 19320498.
14. Li D, Wang F, Xiao X, Zeng X, Gu QQ, Zhu W. A new cytotoxic phenazine derivative from a deep sea bacterium Bacillus sp. Arch Pharm Res 2007, 30:552-555. 10.1007/BF02977647, 17615672.
15. Sagar S, Esau L, Hikmawan T, Antunes A, Holtermann K, Stingl U, Bajic VB, Kaur M. Cytotoxic and apoptotic evaluations of marine bacteria isolated from brine-seawater interface of the Red Sea. BMC Complement Altern Med 2013, 13:29. 10.1186/1472-6882-13-29, 3598566, 23388148.
16. Al-Rikabi A, Husain S. Increasing prevalence of breast cancer among Saudi patients attending a tertiary referral hospital: a retrospective epidemiologic study. Croat Med J 2012, 53:239-243. 10.3325/cmj.2012.53.239, 3370407, 22661137.
17. Rabah DM, Arafa MA. Prostate cancer screening in a Saudi population: an explanatory trial study. Prostate Cancer Prostatic Dis 2010, 13:191-194. 10.1038/pcan.2009.60, 20066007.
18. Sait K, Bentley J, Anfinan N, Power P. Cervical cancer prevention in Saudi Arabia: it is time to call for action!. Open Women's Health J 2012, 6:1-5.
19. Backer H, Schoell M. New deeps with brines and metalliferous sediments in the Red Sea. Nat Physic Sci 1972, 240:153-158.
20. Antunes A, Ngugi DK, Stingl U. Microbiology of the Red Sea (and other) deep-sea anoxic brine lakes. Environ Microbiol Reports 2011, 3:416-433.
21. Hartmann M, Scholten J, Stoffers P, Wehner F. Hydrographic structure of brine-filled deeps in the Red Sea-new results from the Shaban, Kebrit, Atlantis II, and Discovery Deep. Mar Geol 1998, 144:311-330.
22. Kaye JZ, Márquez MC, Ventosa A, Baross JA. Halomonas neptunia sp. nov., Halomonas sulfidaeris sp. nov., Halomonas axialensis sp. nov. and Halomonas hydrothermalis sp. nov.: halophilic bacteria isolated from deep-sea hydrothermal-vent environments. Int J System Evol Microbiol 2004, 54:499-511.
23. Hou S, Saw JH, Lee KS, Freitas TA, Belisle C, Kawarabayasi Y, Donachie SP, Pikina A, Galperin MY, Koonin EV, et al. Genome sequence of the deep-sea gamma-proteobacterium Idiomarina loihiensis reveals amino acid fermentation as a source of carbon and energy. Proc Natl Acad Sci U S A 2004, 101:18036-18041. 10.1073/pnas.0407638102, 539801, 15596722.
24. Hua N-P, Hamza-Chaffai A, Vreeland RH, Isoda H, Naganuma T. Virgibacillus salarius sp. nov., a halophilic bacterium isolated from a Saharan salt lake. Int J Syst Evol Microbiol 2008, 58:2409-2414. 10.1099/ijs.0.65693-0, 18842865.
25. Wang Y-X, Wang Z-G, Liu J-H, Chen Y-G, Zhang X-X, Wen M-L, Xu L-H, Peng Q, Cui X-L. Sediminimonas qiaohouensis gen. nov., sp. nov., a member of the Roseobacter clade in the order Rhodobacterales. Int J Syst Evol Microbiol 2009, 59:1561-1567. 10.1099/ijs.0.006965-0, 19528203.
26. Copeland A, O'Connor K, Lucas S, Lapidus A, Berry KW, Detter JC, Del Rio TG, Hammon N, Dalin E, Tice H, et al. Complete genome sequence of the halophilic and highly halotolerant Chromohalobacter salexigens type strain (1H11(T)). Stand Genomic Sci 2011, 5:379-388. 10.4056/sigs.2285059, 3368415, 22675587.
27. Saum SH, Pfeiffer F, Palm P, Rampp M, Schuster SC, Muller V, Oesterhelt D. Chloride and organic osmolytes: a hybrid strategy to cope with elevated salinities by the moderately halophilic, chloride-dependent bacterium Halobacillus halophilus. Environ Microbiol 2013, 15:1619-1633. 10.1111/j.1462-2920.2012.02770.x, 22583374.
28. Yin Q, Fu B, Li B, Shi X, Inagaki F, Zhang XH. Spatial variations in microbial community composition in surface seawater from the ultra-oligotrophic center to rim of the South Pacific Gyre. PLoS One 2013, 8:e55148. 10.1371/journal.pone.0055148, 3566182, 23405118.
29. Brettar I, Christen R, Hofle MG. Idiomarina baltica sp. nov., a marine bacterium with a high optimum growth temperature isolated from surface water of the central Baltic Sea. Int J Syst Evol Microbiol 2003, 53:407-413. 10.1099/ijs.0.02399-0, 12710605.
30. Qin QL, Zhang XY, Wang XM, Liu GM, Chen XL, Xie BB, Dang HY, Zhou BC, Yu J, Zhang YZ. The complete genome of Zunongwangia profunda SM-A87 reveals its adaptation to the deep-sea environment and ecological role in sedimentary organic nitrogen degradation. BMC Genomics 2010, 11:247. 10.1186/1471-2164-11-247, 2864250, 20398413.
31. Arahal DR, Garcia MT, Ludwig W, Schleifer KH, Ventosa A. Transfer of Halomonas canadensis and Halomonas israelensis to the genus Chromohalobacter as Chromohalobacter canadensis comb. nov. and Chromohalobacter israelensis comb. nov. Int J Syst Evol Microbiol 2001, 51:1443-1448.
32. Gardes A, Kaeppel E, Shehzad A, Seebah S, Teeling H, Yarza P, Glockner FO, Grossart HP, Ullrich MS. Complete genome sequence of Marinobacter adhaerens type strain (HP15), a diatom-interacting marine microorganism. Stand Genomic Sci 2010, 3:97-107. 10.4056/sigs.922139, 3035377, 21304739.
33. Ivanova EP, Romanenko LA, Chun J, Matte MH, Matte GR, Mikhailov VV, Svetashev VI, Huq A, Maugel T, Colwell RR. Idiomarina gen. nov., comprising novel indigenous deep-sea bacteria from the Pacific Ocean, including descriptions of two species, Idiomarina abyssalis sp. nov. and Idiomarina zobellii sp. nov. Int J Syst Evol Microbiol 2000, 50(Pt 2):901-907.
34. Beech F, Davenport R. Isolation, purification and maintenance of yeasts. Meth Microbiol 1971, 4:153.
35. Dieffenbach CW, Dveksler G. PCR primer 1995, Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press.
36. Zhang JH, Chung TD, Oldenburg KR. A simple statistical parameter for Use in evaluation and validation of high throughput screening assays. J Biomol Screen 1999, 4:67-73. 10.1177/108705719900400206, 10838414.
37. Dean E, Greystoke A, Ranson M, Dive C. Biomarkers of cell death applicable to early clinical trials. Exp Cell Res 2012, 318:1252-1259. 10.1016/j.yexcr.2012.03.020, 22483936.
38. Soldani C, Scovassi AI. Poly(ADP-ribose) polymerase-1 cleavage during apoptosis: an update. Apoptosis 2002, 7:321-328. 10.1023/A:1016119328968, 12101391.
39. Bouchard VJ, Rouleau M, Poirier GG. PARP-1, a determinant of cell survival in response to DNA damage. Exp Hematol 2003, 31:446-454. 10.1016/S0301-472X(03)00083-3, 12829019.
40. Kaufmann SH, Desnoyers S, Ottaviano Y, Davidson NE, Poirier GG. Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Res 1993, 53:3976-3985.
41. Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM. Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell 1995, 81:801-809. 10.1016/0092-8674(95)90541-3, 7774019.
42. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 1998, 273:5858-5868. 10.1074/jbc.273.10.5858, 9488723.
43. Rogakou EP, Nieves-Neira W, Boon C, Pommier Y, Bonner WM. Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J Biol Chem 2000, 275:9390-9395. 10.1074/jbc.275.13.9390, 10734083.
44. Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell 2004, 116:205-219. 10.1016/S0092-8674(04)00046-7, 14744432.
45. Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, Griffith C, Boeddinghaus I, Salter J, Detre S, Hills M, et al. Proliferation and apoptosis as markers of benefit in neoadjuvant endocrine therapy of breast cancer. Clin Cancer Res 2006, 12:1024s-1030s. 10.1158/1078-0432.CCR-05-2127, 16467120.
46. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995, 267:1456-1462. 10.1126/science.7878464, 7878464.
47. Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 2011, 30:87. 10.1186/1756-9966-30-87, 3197541, 21943236.
48. Bitzer J, Grosse T, Wang L, Lang S, Beil W, Zeeck A. New aminophenoxazinones from a marine Halomonas sp.: fermentation, structure elucidation, and biological activity. J Antibiot (Tokyo) 2006, 59:86-92. 10.1038/ja.2006.12, 16629408.
49. Ruiz-Ruiz C, Srivastava GK, Carranza D, Mata JA, Llamas I, Santamaria M, Quesada E, Molina IJ. An exopolysaccharide produced by the novel halophilic bacterium Halomonas stenophila strain B100 selectively induces apoptosis in human T leukaemia cells. Appl Microbiol Biotechnol 2011, 89:345-355. 10.1007/s00253-010-2886-7, 20890756.
50. Wang L, Grosse T, Stevens H, Brinkhoff T, Simon M, Liang L, Bitzer J, Bach G, Zeeck A, Tokuda H, Lang S. Bioactive hydroxyphenylpyrrole-dicarboxylic acids from a new marine Halomonas sp.: Production and structure elucidation. Appl Microbiol Biotechnol 2006, 72:816-822. 10.1007/s00253-006-0370-1, 16642332.
51. Donachie SP, Hou S, Gregory TS, Malahoff A, Alam M. Idiomarina loihiensis sp. nov., a halophilic gamma-Proteobacterium from the Lo'ihi submarine volcano, Hawai'i. Int J Syst Evol Microbiol 2003, 53:1873-1879. 10.1099/ijs.0.02701-0, 14657116.
52. van der Horst MA, Stalcup TP, Kaledhonkar S, Kumauchi M, Hara M, Xie A, Hellingwerf KJ, Hoff WD. Locked chromophore analogs reveal that photoactive yellow protein regulates biofilm formation in the deep sea bacterium Idiomarina loihiensis. J Am Chem Soc 2009, 131:17443-17451. 10.1021/ja9057103, 19891493.
53. Mutnuri S, Vasudevan N, Kastner M, Heipieper HJ. Changes in fatty acid composition of Chromohalobacter israelensis with varying salt concentrations. Curr Microbiol 2005, 50:151-154. 10.1007/s00284-004-4396-2, 15717227.
54. Vargas C, Jebbar M, Carrasco R, Blanco C, Calderon MI, Iglesias-Guerra F, Nieto JJ. Ectoines as compatible solutes and carbon and energy sources for the halophilic bacterium Chromohalobacter salexigens. J Appl Microbiol 2006, 100:98-107. 10.1111/j.1365-2672.2005.02757.x, 16405689.
55. Garcia-Estepa R, Argandona M, Reina-Bueno M, Capote N, Iglesias-Guerra F, Nieto JJ, Vargas C. The ectD gene, which is involved in the synthesis of the compatible solute hydroxyectoine, is essential for thermoprotection of the halophilic bacterium Chromohalobacter salexigens. J Bacteriol 2006, 188:3774-3784. 10.1128/JB.00136-06, 1482885, 16707670.
56. Zhao B, Lu W, Yang L, Zhang B, Wang L, Yang SS. Cloning and characterization of the genes for biosynthesis of the compatible solute ectoine in the moderately halophilic bacterium Halobacillus dabanensis D-8(T). Curr Microbiol 2006, 53:183-188. 10.1007/s00284-005-0396-0, 16874550.
57. Bergmann S, David F, Clark W, Wittmann C, Krull R. Membrane fluidity of halophilic ectoine-secreting bacteria related to osmotic and thermal treatment. Bioprocess Biosyst Eng 2013,
58. Ahn JW, Lee SY, Kim S, Kim SM, Lee SB, Kim KJ. Crystal structure of glucuronic acid dehydrogenase [correction of dehydrogeanse] from Chromohalobacter salexigens. Proteins 2012, 80:314-318. 10.1002/prot.23167, 21987458.
59. Ahn JW, Lee SY, Kim S, Cho SJ, Lee SB, Kim KJ. Cloning, expression, purification, crystallization and X-ray crystallographic analysis of glucuronic acid dehydrogenase from Chromohalobacter salexigens. Acta Crystallogr Sect F Struct Biol Cryst Commun 2011, 67:689-691. 10.1107/S1744309111012437, 3107144, 21636913.
60. Ates O, Oner ET, Arga KY. Genome-scale reconstruction of metabolic network for a halophilic extremophile, Chromohalobacter salexigens DSM 3043. BMC Syst Biol 2011, 5:12. 10.1186/1752-0509-5-12, 3034673, 21251315.
61. Pastor JM, Bernal V, Salvador M, Argandona M, Vargas C, Csonka L, Sevilla A, Iborra JL, Nieto JJ, Canovas M. Role of central metabolism in the Osmoadaptation of the halophilic bacterium Chromohalobacter salexigens. J Biol Chem 2013, 288:17769-17781. 10.1074/jbc.M113.470567, 23615905.
62. Konopleva M, Zhao S, Xie Z, Segall H, Younes A, Claxton DF, Estrov Z, Kornblau SM, Andreeff M. Apoptosis. Molecules and mechanisms. Adv Exp Med Biol 1999, 457:217-236. 10.1007/978-1-4615-4811-9_24, 10500797.
63. Zou H, Li Y, Liu X, Wang X. An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 1999, 274:11549-11556. 10.1074/jbc.274.17.11549, 10206961.
64. Schulze-Osthoff K, Ferrari D, Los M, Wesselborg S, Peter ME. Apoptosis signaling by death receptors. Eur J Biochem 1998, 254:439-459. 10.1046/j.1432-1327.1998.2540439.x, 9688254.
65. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 2003, 114:181-190. 10.1016/S0092-8674(03)00521-X, 12887920.
66. Samraj AK, Keil E, Ueffing N, Schulze-Osthoff K, Schmitz I. Loss of caspase-9 provides genetic evidence for the type I/II concept of CD95-mediated apoptosis. J Biol Chem 2006, 281:29652-29659. 10.1074/jbc.M603487200, 16895904.
67. McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Med 2013, 3:a008656.
68. van Engeland M, Nieland LJ, Ramaekers FC, Schutte B, Reutelingsperger CP. Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry 1998, 31:1-9. 10.1002/(SICI)1097-0320(19980101)31:1<1::AID-CYTO1>3.0.CO;2-R, 9450519.
69. D'Sa-Eipper C, Leonard JR, Putcha G, Zheng TS, Flavell RA, Rakic P, Kuida K, Roth KA. DNA damage-induced neural precursor cell apoptosis requires p53 and caspase 9 but neither Bax nor caspase 3. Development 2001, 128:137-146.
70. Shi Y. Activation of initiator caspases: history, hypotheses, and perspectives. J Cancer Mol 2005, 1:9-18.
71. Boulares AH, Yakovlev AG, Ivanova V, Stoica BA, Wang G, Iyer S, Smulson M. Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. J Biol Chem 1999, 274:22932-22940. 10.1074/jbc.274.33.22932, 10438458.
72. Wang ZQ, Stingl L, Morrison C, Jantsch M, Los M, Schulze-Osthoff K, Wagner EF. PARP is important for genomic stability but dispensable in apoptosis. Genes Dev 1997, 11:2347-2358. 10.1101/gad.11.18.2347, 316515, 9308963.
73. Salvesen GS, Dixit VM. Caspases: intracellular signaling by proteolysis. Cell 1997, 91:443-446. 10.1016/S0092-8674(00)80430-4, 9390553.
74. Germain M, Affar EB, D'Amours D, Dixit VM, Salvesen GS, Poirier GG. Cleavage of automodified poly(ADP-ribose) polymerase during apoptosis. Evidence for involvement of caspase-7. J Biol Chem 1999, 274:28379-28384. 10.1074/jbc.274.40.28379, 10497198.
75. Leist M, Single B, Kunstle G, Volbracht C, Hentze H, Nicotera P. Apoptosis in the absence of poly-(ADP-ribose) polymerase. Biochem Biophys Res Commun 1997, 233:518-522. 10.1006/bbrc.1997.6491, 9144569.
76. Stefanis L, Park DS, Yan CY, Farinelli SE, Troy CM, Shelanski ML, Greene LA. Induction of CPP32-like activity in PC12 cells by withdrawal of trophic support. Dissociation from apoptosis. J Biol Chem 1996, 271:30663-30671. 10.1074/jbc.271.48.30663, 8940042.
77. Cryns VL, Bergeron L, Zhu H, Li H, Yuan J. Specific cleavage of alpha-fodrin during Fas- and tumor necrosis factor-induced apoptosis is mediated by an interleukin-1beta-converting enzyme/Ced-3 protease distinct from the poly(ADP-ribose) polymerase protease. J Biol Chem 1996, 271:31277-31282. 10.1074/jbc.271.49.31277, 8940132.
78. Herceg Z, Wang ZQ. Failure of poly(ADP-ribose) polymerase cleavage by caspases leads to induction of necrosis and enhanced apoptosis. Mol Cell Biol 1999, 19:5124-5133. 84355, 10373561.
79. Mah LJ, El-Osta A, Karagiannis TC. GammaH2AX: a sensitive molecular marker of DNA damage and repair. Leukemia 2010, 24:679-686. 10.1038/leu.2010.6, 20130602.
80. Clingen PH, Wu JY, Miller J, Mistry N, Chin F, Wynne P, Prise KM, Hartley JA. Histone H2AX phosphorylation as a molecular pharmacological marker for DNA interstrand crosslink cancer chemotherapy. Biochem Pharmacol 2008, 76:19-27. 10.1016/j.bcp.2008.03.025, 18508035.
81. Wilson AJ, Holson E, Wagner F, Zhang YL, Fass DM, Haggarty SJ, Bhaskara S, Hiebert SW, Schreiber SL, Khabele D. The DNA damage mark pH2AX differentiates the cytotoxic effects of small molecule HDAC inhibitors in ovarian cancer cells. Cancer Biol Ther 2011, 12:484-493. 10.4161/cbt.12.6.15956, 3218590, 21738006.
82. Cheung-Ong K, Giaever G, Nislow C. DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology. Chem Biol 2013, 20:648-659. 10.1016/j.chembiol.2013.04.007, 23706631.