Skip to main content

Advertisement

SpringerLink
Log in

Arsenic-induced prostate cancer: an enigma

  • Review Article
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Arsenic exhibits varying degrees of toxicity depending on its many chemical forms. The carcinogenic properties of arsenic have already been established. However, the precise processes underlying the development of diseases following acute or chronic exposure to arsenic remain poorly known. Most of the existing investigation has focused on studying the occurrence of cancer following significant exposure to elevated levels of arsenic. Nevertheless, multiple investigations have documented diverse health consequences from prolonged exposure to low levels of arsenic. Inorganic arsenic commonly causes lung, bladder, and skin cancer. Some investigations have shown an association between arsenic in drinking water and prostate cancer, but few investigations have focused on exploring this connection. There is currently a lack of relevant animal models demonstrating a clear link between inorganic arsenic exposure and the development of prostate cancer. Nevertheless, studies using cellular model systems have demonstrated that arsenic can potentially promote the malignant transformation of human prostate epithelial cells in vitro. The administration of elevated levels of arsenic has been demonstrated to elicit cell death in instances of acute experimental exposure. Conversely, in cases of chronic exposure, arsenic prompts cellular proliferation and sustains cellular viability, thereby circumventing the constraints imposed by telomere shortening and apoptosis. Furthermore, cells consistently exposed to the stimulus exhibit an augmented ability to invade surrounding tissues and an enhanced potential to form tumors. This review aims to portray mechanistic insights into arsenic-induced prostate cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The articles analyzed during the current study are available in the literature and listed in the references.

Code availability

Not applicable.

References

  1. IARC. “Arsenic, metals, fibres, and dusts.” IARC Monogr Eval Carcinog Risks Hum. 2012;100:11–465.

    Google Scholar 

  2. S. Chou, C. Harper, and L. Ingerman, 2007 “Toxicological profile for arsenic. Atlanta, GA: US Department of Health and Human Services,” Public Health Service, Agency for Toxic Substances and Disease Registry

  3. Goutam Mukherjee A, et al. “Mixed contaminants: occurrence, interactions, toxicity, detection, and remediation.” Molecules. 2022;27(8):2577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bulka CM, Jones RM, Turyk ME, Stayner LT, Argos M. “Arsenic in drinking water and prostate cancer in Illinois counties: an ecologic study.” Environ Res. 2016;148:450–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. A. H. Smith, 2001 “Is the proposed new arsenic water standaard of 10 ug/l sufficiently protective of public health,” ed.

  6. Roh T, Lynch CF, Weyer P, Wang K, Kelly KM, Ludewig G. “Low-level arsenic exposure from drinking water is associated with prostate cancer in Iowa.” Environ Res. 2017;159:338–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ahn J, Boroje IJ, Ferdosi H, Kramer ZJ, Lamm SH. “Prostate cancer incidence in U.S. Counties and low levels of arsenic in drinking water.” Int J Environ Res Pub Health. 2020;17(3):960.

    Article  CAS  Google Scholar 

  8. Waalkes MP, Liu J, Diwan BA. “Transplacental arsenic carcinogenesis in mice.” Toxicol Appl Pharmacol. 2007;222(3):271–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Benbrahim-Tallaa L, Waalkes MP. “Inorganic arsenic and human prostate cancer.” Environ Health Perspect. 2008;116(2):158–64.

    Article  CAS  PubMed  Google Scholar 

  10. Hanlon DP, Ferm VH. “Placental permeability of arsenate ion during early embryogenesis in the hamster.” Experientia. 1977;33(9):1221–2.

    Article  CAS  PubMed  Google Scholar 

  11. Hong YS, Song KH, Chung JY. “Health effects of chronic arsenic exposure.” J Prev Med Public Health. 2014;47(5):245–52.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Tchounwou PB, Patlolla AK, Centeno JA. “Carcinogenic and systemic health effects associated with arsenic exposure–a critical review.” Toxicol Pathol. 2003;31(6):575–88.

    CAS  PubMed  Google Scholar 

  13. Buchet JP, Lauwerys R, Roels H. “Urinary excretion of inorganic arsenic and its metabolites after repeated ingestion of sodium metaarsenite by volunteers.” Int Arch Occup Environ Health. 1981;48(2):111–8.

    Article  CAS  PubMed  Google Scholar 

  14. Mukherjee AG, et al. “The cellular and molecular immunotherapy in prostate cancer.” Vaccines (Basel). 2022. https://doi.org/10.3390/vaccines10081370.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sekhoacha M, Riet K, Motloung P, Gumenku L, Adegoke A, Mashele S. “Prostate cancer review: genetics, diagnosis, treatment options, and alternative approaches.” Molecules. 2022. https://doi.org/10.3390/molecules27175730.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mukherjee AG, Gopalakrishnan AV. “Unlocking the mystery associated with infertility and prostate cancer: an update.” Med Oncol. 2023;40(6):160.

    Article  CAS  PubMed  Google Scholar 

  17. Wen S, Chang HC, Tian J, Shang Z, Niu Y, Chang C. “Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer.” Am J Pathol. 2015;185(2):293–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cittadini A, Isidori AM, Salzano A. “Testosterone therapy and cardiovascular diseases.” Cardiovasc Res. 2022;118(9):2039–57.

    Article  CAS  PubMed  Google Scholar 

  19. Wanjari UR, et al. “Role of metabolism and metabolic pathways in prostate cancer.” Metabolites. 2023. https://doi.org/10.3390/metabo13020183.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hjelmborg JB, et al. “The heritability of prostate cancer in the Nordic Twin Study of Cancer.” Cancer Epidemiol Biomarkers Prev. 2014;23(11):2303–10.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bluemn EG, Nelson PS. “The androgen/androgen receptor axis in prostate cancer.” Curr Opin Oncol. 2012;24(3):251–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ziaran S, Varchulova Novakova Z, Bohmer D, Danisovic L. Biomarkers for determination prostate cancer: implication for diagnosis and prognosis”. Neoplasma. 2015;62(5):683–91.

    Article  CAS  PubMed  Google Scholar 

  23. Benbrahim-Tallaa L, Webber MM, Waalkes MP. “Acquisition of androgen independence by human prostate epithelial cells during arsenic-induced malignant transformation,.” Environ Health Perspect. 2005;113(9):1134–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Benbrahim-Tallaa L, Webber MM, Waalkes MP. “Mechanisms of acquired androgen independence during arsenic-induced malignant transformation of human prostate epithelial cells.” Environ Health Perspect. 2007;115(2):243–7.

    Article  CAS  PubMed  Google Scholar 

  25. Tokar EJ, Diwan BA, Waalkes MP. “Arsenic exposure transforms human epithelial stem/progenitor cells into a cancer stem-like phenotype.” Environ Health Perspect. 2010;118(1):108–15.

    Article  CAS  PubMed  Google Scholar 

  26. Xu Y, Tokar EJ, Sun Y, Waalkes MP. “Arsenic-transformed malignant prostate epithelia can convert noncontiguous normal stem cells into an oncogenic phenotype.” Environ Health Perspect. 2012;120(6):865–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. J. Centeno, M. Gray, J. Mullick, P. Tchounwou, and C. Tseng, 2005 “Arsenic in drinking water and health issues. Treatments and effects in ecology and human health,” ed: Resolution Press, Christ Church.

  28. Abernathy CO, et al. “Arsenic: health effects, mechanisms of actions, and research issues.” Environ Health Perspect. 1999;107(7):593–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mukherjee AG, Valsala Gopalakrishnan A. “The interplay of arsenic, silymarin, and NF-ĸB pathway in male reproductive toxicity: a review.” Ecotoxicol Environ Saf. 2023;252:114614.

    Article  CAS  PubMed  Google Scholar 

  30. Hughes MF. “Arsenic toxicity and potential mechanisms of action.” Toxicol Lett. 2002;133(1):1–16.

    Article  CAS  PubMed  Google Scholar 

  31. J. A. Centeno et al., 2006 “Environmental pathology and health effects of arsenic poisoning,” in Managing arsenic in the environment: from soil to human health, pp. 311–327.

  32. 1980 “Arsenic and arsenic compounds,”, IARC Monogr Eval Carcinog Risk Chem Hum, 23: 39–141

  33. Szymańska JA, Chmielnicka J. “[Health effects of exposure of humans to inorganic arsenic compounds],” (in pol). Med Pr. 1991;42(3):199–206.

    PubMed  Google Scholar 

  34. Kapaj S, Peterson H, Liber K, Bhattacharya P. “Human health effects from chronic arsenic poisoning–a review.” J Environ Sci Health A Tox Hazard Subst Environ Eng. 2006;41(10):2399–428.

    Article  CAS  PubMed  Google Scholar 

  35. Chen CJ, Kuo TL, Wu MM. “Arsenic and cancers.” Lancet. 1988;1(8582):414–5.

    Article  CAS  PubMed  Google Scholar 

  36. Kurokawa M, et al. “Investigation of skin manifestations of arsenicism due to intake of arsenic-contaminated groundwater in residents of Samta, Jessore, Bangladesh.” Arch Dermatol. 2001;137(1):102–3.

    CAS  PubMed  Google Scholar 

  37. Smith AH, Goycolea M, Haque R, Biggs ML. “Marked increase in bladder and lung cancer mortality in a region of Northern Chile due to arsenic in drinking water.” Am J Epidemiol. 1998;147(7):660–9.

    Article  CAS  PubMed  Google Scholar 

  38. Hopenhayn-Rich C, Biggs ML, Smith AH. “Lung and kidney cancer mortality associated with arsenic in drinking water in Córdoba, Argentina,.” Int J Epidemiol. 1998;27(4):561–9.

    Article  CAS  PubMed  Google Scholar 

  39. States JC, Barchowsky A, Cartwright IL, Reichard JF, Futscher BW, Lantz RC. “Arsenic toxicology: translating between experimental models and human pathology.” Environ Health Perspect. 2011;119(10):1356–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pi J, et al. “Decreased serum concentrations of nitric oxide metabolites among Chinese in an endemic area of chronic arsenic poisoning in inner Mongolia.” Free Radic Biol Med. 2000;28(7):1137–42.

    Article  CAS  PubMed  Google Scholar 

  41. Gonsebatt ME, et al. “Lymphocyte replicating ability in individuals exposed to arsenic via drinking water.” Mutat Res. 1994;313(2–3):293–9.

    Article  CAS  PubMed  Google Scholar 

  42. Gonsebatt ME, et al. “Cytogenetic effects in human exposure to arsenic.” Mutat Res. 1997;386(3):219–28.

    Article  CAS  PubMed  Google Scholar 

  43. States JC. “Translating experimental data to human populations,” in arsenic: exposure sources. Health Risks Mech Toxicity. 2015;2015:535–48.

    Google Scholar 

  44. Nail AN, Ferragut Cardoso AP, Montero LK, States JC. “miRNAs and arsenic-induced carcinogenesis.” Adv Pharmacol. 2023;96:203–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cohen SM, Arnold LL, Beck BD, Lewis AS, Eldan M. “Evaluation of the carcinogenicity of inorganic arsenic.” Crit Rev Toxicol. 2013;43(9):711–52.

    Article  CAS  PubMed  Google Scholar 

  46. Cohen SM, Arnold LL, Eldan M, Lewis AS, Beck BD. “Methylated arsenicals: the implications of metabolism and carcinogenicity studies in rodents to human risk assessment.” Crit Rev Toxicol. 2006;36(2):99–133.

    Article  CAS  PubMed  Google Scholar 

  47. Cohen SM, Purtilo DT, Ellwein LB. “Ideas in pathology Pivotal role of increased cell proliferation in human carcinogenesis.” Mod Pathol. 1991;4(3):371–82.

    CAS  PubMed  Google Scholar 

  48. Tokar EJ, et al. “Arsenic-specific stem cell selection during malignant transformation.” J Natl Cancer Inst. 2010;102(9):638–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Achanzar WE, Brambila EM, Diwan BA, Webber MM, Waalkes MP. “Inorganic arsenite-induced malignant transformation of human prostate epithelial cells.” J Natl Cancer Inst. 2002;94(24):1888–91.

    Article  CAS  PubMed  Google Scholar 

  50. Waalkes MP, et al. “Arsenic exposure in utero exacerbates skin cancer response in adulthood with contemporaneous distortion of tumor stem cell dynamics.” Cancer Res. 2008;68(20):8278–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sun Y, Tokar EJ, Waalkes MP. “Overabundance of putative cancer stem cells in human skin keratinocyte cells malignantly transformed by arsenic.” Toxicol Sci. 2012;125(1):20–9.

    Article  CAS  PubMed  Google Scholar 

  52. Tokar EJ, Diwan BA, Ward JM, Delker DA, Waalkes MP. “Carcinogenic effects of ‘whole-life’ exposure to inorganic arsenic in CD1 mice.” Toxicol Sci. 2011;119(1):73–83.

    Article  CAS  PubMed  Google Scholar 

  53. Ngalame NN, Makia NL, Waalkes MP, Tokar EJ. “Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration.” Toxicol Appl Pharmacol. 2016;312:11–8.

    Article  CAS  PubMed  Google Scholar 

  54. Dodson M, et al. “Low-level arsenic causes proteotoxic stress and not oxidative stress.” Toxicol Appl Pharmacol. 2018;341:106–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lau A, Whitman SA, Jaramillo MC, Zhang DD. “Arsenic-mediated activation of the Nrf2-Keap1 antioxidant pathway.” J Biochem Mol Toxicol. 2013;27(2):99–105.

    Article  CAS  PubMed  Google Scholar 

  56. Clewell HJ, et al. “Concentration- and time-dependent genomic changes in the mouse urinary bladder following exposure to arsenate in drinking water for up to 12 weeks.” Toxicol Sci. 2011;123(2):421–32.

    Article  CAS  PubMed  Google Scholar 

  57. García-Esquinas E, et al. “Arsenic exposure and cancer mortality in a US-based prospective cohort: the strong heart study.” Cancer Epidemiol Biomarkers Prev. 2013;22(11):1944–53.

    Article  PubMed  Google Scholar 

  58. Yang CY, Chang CC, Chiu HF. “Does arsenic exposure increase the risk for prostate cancer?” J Toxicol Environ Health A. 2008;71(23):1559–63.

    Article  CAS  PubMed  Google Scholar 

  59. Román MD, Niclis C, Aballay LR, Lantieri MJ, Díaz MDP, Muñoz SE. “Do exposure to arsenic, occupation and diet have synergistic effects on prostate cancer risk?” Asian Pac J Cancer Prev. 2018;19(6):1495–501.

    PubMed  PubMed Central  Google Scholar 

  60. Kojima C, et al. “Requirement of arsenic biomethylation for oxidative DNA damage.” J Natl Cancer Inst. 2009;101(24):1670–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Bardach AE, et al. “Epidemiology of chronic disease related to arsenic in Argentina: a systematic review.” Sci Total Environ. 2015;538:802–16.

    Article  CAS  PubMed  Google Scholar 

  62. Brown KG, Ross GL. “Arsenic, drinking water, and health: a position paper of the American Council on Science and Health.” Regul Toxicol Pharmacol. 2002;36(2):162–74.

    Article  CAS  PubMed  Google Scholar 

  63. Chen CJ, Wang CJ. “Ecological correlation between arsenic level in well water and age-adjusted mortality from malignant neoplasms.” Cancer Res. 1990;50(17):5470–4.

    CAS  PubMed  Google Scholar 

  64. Gunduz O, et al. “Statistical analysis of causes of death (2005–2010) in villages of Simav Plain, Turkey, with high arsenic levels in drinking water supplies.” Arch Environ Occup Health. 2015;70(1):35–46.

    Article  PubMed  Google Scholar 

  65. Hinwood AL, Jolley DJ, Sim MR. “Cancer incidence and high environmental arsenic concentrations in rural populations: results of an ecological study.” Int J Environ Health Res. 1999;9(2):131–41.

    Article  CAS  Google Scholar 

  66. Lewis DR, Southwick JW, Ouellet-Hellstrom R, Rench J, Calderon RL. “Drinking water arsenic in Utah: a cohort mortality study.” Environ Health Perspect. 1999;107(5):359–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Núñez O, Fernández-Navarro P, Martín-Méndez I, Bel-Lan A, Locutura JF, López-Abente G. “Arsenic and chromium topsoil levels and cancer mortality in Spain.” Environ Sci Pollut Res Int. 2016;23(17):17664–75.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Rivara MI, Cebrián M, Corey G, Hernández M, Romieu I. Cancer risk in an arsenic-contaminated area of Chile”. Toxicol Ind Healt. 1997;13(2–3):321–38.

    Article  CAS  Google Scholar 

  69. Wu MM, Kuo TL, Hwang YH, Chen CJ. “Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases.” Am J Epidemiol. 1989;130(6):1123–32.

    Article  CAS  PubMed  Google Scholar 

  70. Keltie E, et al. “Arsenic speciation and metallomics profiling of human toenails as a biomarker to assess prostate cancer cases: Atlantic PATH cohort study.” Front Public Health. 2022;10: 818069.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Tsai SM, Wang TN, Ko YC. “Mortality for certain diseases in areas with high levels of arsenic in drinking water.” Arch Environ Health. 1999;54(3):186–93.

    Article  CAS  PubMed  Google Scholar 

  72. Tibbetts J. “Arsenic and prostate cancer: acquiring androgen independence.” Environ Health Sci. 2005. https://doi.org/10.1289/ehp.113-a614b.

    Article  Google Scholar 

  73. Andrew AS, et al. “Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic.” Environ Health Perspect. 2006;114(8):1193–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Baastrup R, et al. “Arsenic in drinking-water and risk for cancer in Denmark.” Environ Health Perspect. 2008;116(2):231–7.

    Article  CAS  PubMed  Google Scholar 

  75. Brawley OW. “Trends in prostate cancer in the United States.” J Natl Cancer Inst Monogr. 2012;2012(45):152–6.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Hsueh YM, et al. “Levels of plasma selenium and urinary total arsenic interact to affect the risk for prostate cancer.” Food Chem Toxicol. 2017;107(Pt A):167–75.

    Article  CAS  PubMed  Google Scholar 

  77. Shearer JJ, Wold EA, Umbaugh CS, Lichti CF, Nilsson CL, Figueiredo ML. “Inorganic arsenic-related changes in the stromal tumor microenvironment in a prostate cancer cell-conditioned media model.” Environ Health Perspect. 2016;124(7):1009–15.

    Article  CAS  PubMed  Google Scholar 

  78. Zimta AA, et al. “Biological and molecular modifications induced by cadmium and arsenic during breast and prostate cancer development.” Environ Res. 2019;178: 108700.

    Article  CAS  PubMed  Google Scholar 

  79. Bosland MC. “Testosterone treatment is a potent tumor promoter for the rat prostate.” Endocrinology. 2014;155(12):4629–33.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Bosland MC, Schlicht MJ, Horton L, McCormick DL. “The MNU plus testosterone rat model of prostate carcinogenesis.” Toxicol Pathol. 2022;50(4):478–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Reddy PS, Rani GP, Sainath SB, Meena R, Supriya C. “Protective effects of N-acetylcysteine against arsenic-induced oxidative stress and reprotoxicity in male mice.” J Trace Elem Med Biol. 2011;25(4):247–53.

    Article  CAS  PubMed  Google Scholar 

  82. Burns FJ, Uddin AN, Wu F, Nádas A, Rossman TG. “Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: a dose-response study.” Environ Health Perspect. 2004;112(5):599–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bosland MC, Horton L. “Sodium arsenite does not affect prostate carcinogenesis in a chemically-hormonally-induced rat model.” Toxicology. 2022;474:153212.

    Article  CAS  PubMed  Google Scholar 

  84. El-Atta HM, et al. “DNA fragmentation, caspase 3 and prostate-specific antigen genes expression induced by arsenic, cadmium, and chromium on nontumorigenic human prostate cells.” Biol Trace Elem Res. 2014;162(1–3):95–105.

    Article  CAS  PubMed  Google Scholar 

  85. Pelch KE, Tokar EJ, Merrick BA, Waalkes MP. “Differential DNA methylation profile of key genes in malignant prostate epithelial cells transformed by inorganic arsenic or cadmium.” Toxicol Appl Pharmacol. 2015;286(3):159–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Singh B, Kulawiec M, Owens KM, Singh A, Singh KK. “Sustained early disruption of mitochondrial function contributes to arsenic-induced prostate tumorigenesis.” Biochemistry (Mosc). 2016;81(10):1089–100.

    Article  CAS  PubMed  Google Scholar 

  87. Benbrahim-Tallaa L, Waterland RA, Styblo M, Achanzar WE, Webber MM, Waalkes MP. “Molecular events associated with arsenic-induced malignant transformation of human prostatic epithelial cells: aberrant genomic DNA methylation and K-ras oncogene activation.” Toxicol Appl Pharmacol. 2005;206(3):288–98.

    Article  CAS  PubMed  Google Scholar 

  88. Yao Y, Dai W. “Genomic instability and cancer.” J Carcinog Mutagen. 2014. https://doi.org/10.4172/2157-2518.1000165.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Bianchi NO, Bianchi MS, Richard SM. “Mitochondrial genome instability in human cancers.” Mutat Res. 2001;488(1):9–23.

    Article  CAS  PubMed  Google Scholar 

  90. Loenen WA. “S-adenosylmethionine: jack of all trades and master of everything?” Biochem Soc Trans. 2006;34(Pt 2):330–3.

    Article  CAS  PubMed  Google Scholar 

  91. Zhao CQ, Young MR, Diwan BA, Coogan TP, Waalkes MP. “Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression.” Proc Natl Acad Sci U S A. 1997;94(20):10907–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Stirzaker C, Song JZ, Davidson B, Clark SJ. “Transcriptional gene silencing promotes DNA hypermethylation through a sequential change in chromatin modifications in cancer cells.” Cancer Res. 2004;64(11):3871–7.

    Article  CAS  PubMed  Google Scholar 

  93. Counts JL, Goodman JI. “Hypomethylation of DNA: a nongenotoxic mechanism involved in tumor promotion.” Toxicol Lett. 1995;82–83:663–72.

    Article  PubMed  Google Scholar 

  94. Vorce RL, Goodman JI. “Altered methylation of ras oncogenes in benzidine-induced B6C3F1 mouse liver tumors.” Toxicol Appl Pharmacol. 1989;100(3):398–410.

    Article  CAS  PubMed  Google Scholar 

  95. Benbrahim-Tallaa L, Waterland RA, Dill AL, Webber MM, Waalkes MP. “Tumor suppressor gene inactivation during cadmium-induced malignant transformation of human prostate cells correlates with overexpression of de novo DNA methyltransferase.” Environ Health Perspect. 2007;115(10):1454–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Wang Z, Yang C. “Metal carcinogen exposure induces cancer stem cell-like property through epigenetic reprograming: a novel mechanism of metal carcinogenesis.” Semin Cancer Biol. 2019;57:95–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Yu Z, Pestell TG, Lisanti MP, Pestell RG. “Cancer stem cell.” Int J Biochem Cell Biol. 2012;44(12):2144–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Ngalame NNO, Luz AL, Makia N, Tokar EJ. “Arsenic alters exosome quantity and cargo to mediate stem cell recruitment into a cancer stem cell-like phenotype.” Toxicol Sci. 2018;165(1):40–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Treas JN, Tyagi T, Singh KP. “Effects of chronic exposure to arsenic and estrogen on epigenetic regulatory genes expression and epigenetic code in human prostate epithelial cells.” PLoS ONE. 2012;7(8): e43880.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Pardal R, Clarke MF, Morrison SJ. “Applying the principles of stem-cell biology to cancer.” Nat Rev Cancer. 2003;3(12):895–902.

    Article  CAS  PubMed  Google Scholar 

  101. Donnenberg VS, Luketich JD, Landreneau RJ, DeLoia JA, Basse P, Donnenberg AD. “Tumorigenic epithelial stem cells and their normal counterparts.” Ernst Schering Found Symp Proc. 2006;5:245–63.

    Google Scholar 

  102. Donnenberg VS, Landreneau RJ, Donnenberg AD. “Tumorigenic stem and progenitor cells: implications for the therapeutic index of anti-cancer agents.” J Control Release. 2007;122(3):385–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Yang Y, McDonald AC, Wang X, Pan Y, Wang M. “Arsenic exposures and prostate cancer risk: a multilevel meta-analysis.” J Trace Elem Med Biol. 2022;72: 126992.

    Article  CAS  PubMed  Google Scholar 

  104. Ngalame NN, Tokar EJ, Person RJ, Waalkes MP. “Silencing KRAS overexpression in arsenic-transformed prostate epithelial and stem cells partially mitigates malignant phenotype.” Toxicol Sci. 2014;142(2):489–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Li D, et al. “A systematic review and meta-analysis of bidirectional effect of arsenic on ERK signaling pathway.” Mol Med Rep. 2018;17(3):4422–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Lau AT, Li M, Xie R, He QY, Chiu JF. “Opposed arsenite-induced signaling pathways promote cell proliferation or apoptosis in cultured lung cells.” Carcinogenesis. 2004;25(1):21–8.

    Article  CAS  PubMed  Google Scholar 

  107. Weber MJ, Gioeli D. “Ras signaling in prostate cancer progression.” J Cell Biochem. 2004;91(1):13–25.

    Article  CAS  PubMed  Google Scholar 

  108. Feldman BJ, Feldman D. “The development of androgen-independent prostate cancer.” Nat Rev Cancer. 2001;1(1):34–45.

    Article  CAS  PubMed  Google Scholar 

  109. Gioeli D. “Signal transduction in prostate cancer progression.” Clin Sci (Lond). 2005;108(4):293–308.

    Article  CAS  PubMed  Google Scholar 

  110. Carter BS, Epstein JI, Isaacs WB. “ras gene mutations in human prostate cancer.” Cancer Res. 1990;50(21):6830–2.

    CAS  PubMed  Google Scholar 

  111. McCubrey JA, et al. “Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance.” Adv Enzyme Regul. 2006;46:249–79.

    Article  CAS  PubMed  Google Scholar 

  112. Ngalame NN, Tokar EJ, Person RJ, Xu Y, Waalkes MP. “Aberrant microRNA expression likely controls RAS oncogene activation during malignant transformation of human prostate epithelial and stem cells by arsenic.” Toxicol Sci. 2014;138(2):268–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Ji H, et al. “Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer.” Cancer Sci. 2014;105(12):1541–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Chiu HW, Chen YA, Ho SY, Wang YJ. “Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells.” PLoS ONE. 2012;7(2): e31579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Xu B, et al. “miR-143 decreases prostate cancer cells proliferation and migration and enhances their sensitivity to docetaxel through suppression of KRAS.” Mol Cell Biochem. 2011;350(1–2):207–13.

    Article  CAS  PubMed  Google Scholar 

  116. Clapé C, et al. “miR-143 interferes with ERK5 signaling, and abrogates prostate cancer progression in mice.” PLoS One. 2009;4(10):e7542.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Reya T, Morrison SJ, Clarke MF, Weissman IL. “Stem cells, cancer, and cancer stem cells.” Nature. 2001;414(6859):105–11.

    Article  CAS  PubMed  Google Scholar 

  118. Leong KG, Gao WQ. “The Notch pathway in prostate development and cancer.” Differentiation. 2008;76(6):699–716.

    Article  CAS  PubMed  Google Scholar 

  119. Lessard J, Sauvageau G. “Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells.” Nature. 2003;423(6937):255–60.

    Article  CAS  PubMed  Google Scholar 

  120. Huss WJ, Gray DR, Greenberg NM, Mohler JL, Smith GJ. “Breast cancer resistance protein-mediated efflux of androgen in putative benign and malignant prostate stem cells.” Cancer Res. 2005;65(15):6640–50.

    Article  CAS  PubMed  Google Scholar 

  121. Zhou S, et al. “The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype.” Nat Med. 2001;7(9):1028–34.

    Article  CAS  PubMed  Google Scholar 

  122. Hochedlinger K, Yamada Y, Beard C, Jaenisch R. “Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues.” Cell. 2005;121(3):465–77.

    Article  CAS  PubMed  Google Scholar 

  123. Huang S, Guo W, Tang Y, Ren D, Zou X, Peng X. “miR-143 and miR-145 inhibit stem cell characteristics of PC-3 prostate cancer cells.” Oncol Rep. 2012;28(5):1831–7.

    Article  CAS  PubMed  Google Scholar 

  124. Al-Eryani L, et al. “Differentially expressed mRNA targets of differentially expressed miRNAs predict changes in the TP53 axis and carcinogenesis-related pathways in human keratinocytes chronically exposed to arsenic.” Toxicol Sci. 2018;162(2):645–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Dezhong L, et al. “miR-150 is a factor of survival in prostate cancer patients.” J buon. 2015;20(1):173–9.

    PubMed  Google Scholar 

  126. Zhou Q, Xi S. “A review on arsenic carcinogenesis: epidemiology, metabolism, genotoxicity and epigenetic changes.” Regul Toxicol Pharmacol. 2018;99:78–88.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank the VIT, Vellore, Tamil Nadu, India, for providing all the facilities to carry out this work.

Funding

No funding was received.

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India

    Anirban Goutam Mukherjee & Abilash Valsala Gopalakrishnan

Authors
  1. Anirban Goutam Mukherjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abilash Valsala Gopalakrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, AVG.; resources and data curation, AGM; writing—original draft preparation, AGM; writing—review and editing, AVG, AGM; visualization, AVG; supervision, AVG; project administration, AVG. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Abilash Valsala Gopalakrishnan.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

We assure you this manuscript has not been published in part or whole or is under consideration for publication elsewhere in any language. All the authors have thoroughly studied the manuscript and approved its consent and submission to the "Medical Oncology" journal.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mukherjee, A.G., Gopalakrishnan, A.V. Arsenic-induced prostate cancer: an enigma. Med Oncol 41, 50 (2024). https://doi.org/10.1007/s12032-023-02266-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-023-02266-5

Keywords

Search

Navigation