Skip to main content

Advertisement

SpringerLink
Log in

Low-concentration BPAF- and BPF-induced cell biological effects are mediated by ROS in MCF-7 breast cancer cells

  • Environmental Quality Benchmarks for Aquatic Ecosystem Protection: Derivation and Application
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Reactive oxygen species (ROS) induced by bisphenol A (BPA) have been implicated in cellular oxidative damage and carcinogenesis. It is not known whether the potential alternatives of BPA, bisphenol AF (BPAF), and bisphenol F (BPF) can also induce ROS involved in mediating biological responses. This study evaluated the toxicity of BPAF and BPF on cell proliferation, DNA damage, intracellular calcium homeostasis, and ROS generation in MCF-7 human breast cancer cells. The results showed that BPAF at 0.001–1 μM and BPF at 0.01–1 μM significantly increased cell viability and at 25 and 50 μM, both compounds decreased cell viability. At 0.01–10 μM, both BPAF and BPF increased DNA damage and significantly elevated ROS and intracellular Ca2+ levels in MCF-7 cells. These biological effects were attenuated by the ROS scavenger N-acetylcysteine (NAC), indicating that ROS played a key role in the observed biological effects of BPAF and BPF on MCF-7 cells. These findings can deepen our understanding on the toxicity of BPAF and BPF, and provide basis data to further evaluate the potential health harm and establish environmental standard of BPAF and BPF.

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
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • An J, Zou W, Zhong YF, Zhang XY, Wu MH, Yu ZQ, Ye TW (2012) The toxic effects of Aroclor 1254 exposure on the osteoblastic cell line MC3T3-E1 and its molecular mechanism. Toxicology 295:8–14

    Article  CAS  Google Scholar 

  • Audebert M, Dolo L, Perdu E, Cravedi JP, Zalko D (2011) Use of the γH2AX assay for assessing the genotoxicity of bispenol a and bisphenol F in human cell lines. Arch Toxicol 85:1463–1473

    Article  CAS  Google Scholar 

  • Cabaton N, Dumont C, Severin I, Perdu E, Zalko D, Cherkaoui-Malki M, Chagnon MC (2009) Genotoxic and endocrine activities of bis(hydroxyphenyl)methane(bisphenol F) and its derivatives in the HepG2 cell line. Toxicology 255:15–24

    Article  CAS  Google Scholar 

  • Cho YJ, Park SB, Han M (2015) Di-(2-ethylhexyl)-phthalate induces oxidative stress in human endometrial stromal cells in vitro. Mol Cell Endocrinol 407:9–17

    Article  CAS  Google Scholar 

  • Danzl E, Sei K, Soda S, Ike M, Fujita M (2009) Biodegradation of bisphenol a, bisphenol F and bisphenol S in seawater. Int J Environ Res Public Health 6:1472–1484

    Article  CAS  Google Scholar 

  • Felty Q, Roy D (2004) Mitochondrial signals to nucleus regulate estrogen-induced cell growth. Med. Hypotheses 64:133–141

    Article  Google Scholar 

  • Felty Q, Xiong WC, Sun D, Sarkar S, Singh KP, Parkash J, Roy D (2005) Estrogen-induced mitochondrial reactive oxygen species as signal-transducing messengers. Biochemistry 44:6900–6909

    Article  CAS  Google Scholar 

  • Feng YX, Yin J, Jiao ZH, Shi JC, Li M, Shao B (2012) Bisphenol AF may cause testosterone reduction by directly affecting testis function in adult male rats. Toxicol Lett 211:201–209

    Article  CAS  Google Scholar 

  • Fic A, Žegura B, Dolenc MS, Filipic M, Mašic LP (2013) Mutagenicity and DNA damage of bisphenol a and its structural analogues in HepG2 cells. Arh Hig Rada Toksikol 64:189–200

    Article  CAS  Google Scholar 

  • Fic A, Zegura B, Gramec D, Mašic LP (2014) Estrogenic and androgenic activities of TBBPA and TBMEPH, metabolites of novel brominated flame retardants, and selected bisphenols, using the XenoScreen XL YES/YAS assay. Chemosphere 112:362–369

    Article  CAS  Google Scholar 

  • Gallart-Ayala H, Moyano E, Galceran MT (2011) Analysis of bisphenols in soft drinks by on-line solid phase extraction fast liquid chromatography-tandem mass spectrometry. Anal Chim Acta 683:227–233

    Article  CAS  Google Scholar 

  • García MA, Peňa D, Alvarez L, Cocca C, Pontillo C, Bergoc R, De Pisarev DK, Randi A (2010) Hexachlorobenzene induces cell proliferation and IGF-I signaling pathway in an estrogen receptor α-dependent manner in MCF-7 breast cancer cell line. Toxicol Lett 192:195–205

    Article  Google Scholar 

  • Ge LC, Chen ZH, Liu H, Zhang KS, Su Q, Ma XY, Huang HB, Zhao ZD, Wang YY, Giesy JP, Wang HS (2014) Signaling related with biphasic effects of bisphenol a (BPA) on Sertoli cell proliferation: a comparative proteomic analysis. Biochim Biophys Acta 1840:2663–2673

    Article  CAS  Google Scholar 

  • Halliwell B (2007) Oxidative stress and cancer: have we moved forward? Biochem J 401:1–11

    Article  CAS  Google Scholar 

  • Han S, Wang CW, Wang WL, Jiang J (2014) Mitogen-activated protein kinase 6 controls root growth in Arabidopsis by modulating Ca2+ based Na+ flux in root cell under salt stress. J Plant Physiol 171:26–34

    Article  CAS  Google Scholar 

  • Healy BF, English KR, Jagals P, Sly PD (2015) Bisphenol a expsore pathways in early childhood: reviewing the need for improved risk assessment models (review). J Expo Sci Env Epid 25:544–556

    Article  CAS  Google Scholar 

  • Huang C-C, Aronstam RS, Chen D-R, Huang Y-W (2010) Oxidative stress, calcium homeostasis, and altered gene expression in human lung epithelial cells exposed to ZnO nanoparticles. Toxicol in Vitro 24:45–55

    Article  CAS  Google Scholar 

  • Kim K-H, Kim J-Y, Kwak J-H, Pyo S (2015) Different anticancer effects of Saxifragifolin a on estrogen receptor-positive and estrogen receptor-negative breast cancer cells. Phytomedicine 22:820–828

    Article  CAS  Google Scholar 

  • Klaunig JE, Kamendulis LM, Hocevar BA (2010) Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol 38:96–109

    Article  CAS  Google Scholar 

  • Lata K, Mukherjee TK (2014) Knockdown of receptor for advanced glycation end products attenuate 17α-ethinyl-estradiol dependent proliferation and survival of MCF-7 breast cancer cells. Biochim Biophys Acta 1840:1083–1091

    Article  CAS  Google Scholar 

  • Lee S, Kim YK, Shin TY, Kim SH (2013) Neurotoxic effects of bisphenol AF on calcium-induced ROS and MAPKs. Neurotox Res 23:249–259

    Article  CAS  Google Scholar 

  • Lei BL, Xu J, Peng W, Wen Y, Zeng XY, Yu ZQ, Wang YP, Chen T (2017a) In vitro profiling of toxicity and endocrine disrupting effects of bisphenol analogues by employing MCF-7 cell and two-hybrid yeast bioassay. Environ Toxicol 32:278–289

    Article  CAS  Google Scholar 

  • Lei BL, Peng W, Xu G, Wu MH, Wen Y, Xu J, Yu ZQ, Wang YP (2017b) Activation of G protein-coupled receptor 30 by thiodiphenol promotes proliferation of estrogen receptor α-positive breast cancer cells. Chem Aust 169:204–211

    CAS  Google Scholar 

  • Li M, Guo J, Gao WH, Yu JL, Han XY, Zhang J, Shao B (2014) Bisphenol AF-induced endogenous transcription is mediated by ERα and ERK1/2 activation in human breast cancer cells. PLOS one 9. Doi:10.1371/journal.pone.0094725

  • Li N, Xia T, Nel AE (2008) The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic Biol Med 44:1689–1699

    Article  CAS  Google Scholar 

  • Liao CY, Kannan K (2013) Concentrations and profiles of bisphenol a and other bisphenol analogues in foodstuffs from the United States and their implications for human exposure. J Agr Food Chem 61:4655–4662

    Article  CAS  Google Scholar 

  • Liao CY, Liu F, Guo Y, Moon HB, Nakata H, Wu Q, Kannan K (2012b) Occurrence of eight bisphenol analogues in indoor dust from the United States and several Asian countries: implications for human exposure. Environ Sci Technol 46:9138–9145

    Article  CAS  Google Scholar 

  • Liao CY, Liu F, Moon HB, Yamashita N, Yun S, Kannan K (2012a) Bisphenol analogues in sediments from industrialized areas in the United States, Japan, and Korea: spatial and temporal distribution. Environ Sci Technol 46:11558–11565

    Article  CAS  Google Scholar 

  • Liu SL, Lin X, Shi DY, Cheng J, Wu CQ, Zhang YD (2002) Reactive oxygen species stimulated human hepatoma cell proliferation via cross-talk between PI3-K/PKB and JNK signaling pathways. Arch Biochem Biophys 406:173–182

    Article  CAS  Google Scholar 

  • Mahalingaiah PKS, Singh MKP (2014) Chronic oxidative stress increase growth and tumorigenic potential of MCF-7 breast cancer cells. PLoS One 9. doi:10.1371/journal.pone.008737.too1

  • Mokra K, Kocia M, Michalowicz J (2015) Bisphenol a and its analogs exhibit different apoptotic potential in peripheral blood mononuclear cells (in vitro study). Food Chem Toxicol 84:79–88

    Article  CAS  Google Scholar 

  • Muchekehu RW, Harvey BJ (2008) 17β-estradiol rapidly mobilizes intracellular calcium from ryanodine-receptor-gated stores via a PKC-PKA-Erk-dependent pathway in the human eccrine sweat gland cell line NCL-SG3. Cell Calcium 44:276–288

    Article  CAS  Google Scholar 

  • Pan F, Xu T, Yang LJ, Jiang XQ, Zhang L (2014) Probing the binding of an endocrine disrupting compound-bisphenol F to human serum albumin: insights into the interactions of harmful chemicals with functional biomacromolecules. Spectrochim. Acta A 132:795–802

    Article  CAS  Google Scholar 

  • Pisapia L, Del Pozzo G, Barba P, Caputo L, Mita L, Viaggiano E, Russo GL, Nicolucci C, Rossi S, Bencivenga U, Mita DG, Diano N (2012) Effects of some endocrine disruptors on cell cycle progression and murine dendritic cell differentiation. Gen Comp Endrocrinol 178:54–63

    Article  CAS  Google Scholar 

  • Pupo M, Pisano A, Lappano R, Santolla MF, De Francesco EM, Abonante S, Rosano C, Maggiolini M (2012) Bisphenol A induces gene expression changes and proliferative effects through GPER in breast cancer cells and cancer associated fibroblasts. Environ Health Perspect 120:1177–1187

  • Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER (2005) A transmembrane intracellular estrogen receptor mediates rapid cell signalling. Science 307:1625–1630

  • Roy D, Cai QY, Felty Q, Narayan S (2007) Estrogen-induced generation of reactive oxygen and nitrogen species, gene damage, and estrogen-dependent cancers. J. Toxicol. Environ. Health B Crit Rev 10:235–257

    CAS  Google Scholar 

  • Ruan T, Liang D, Song SJ, Song MY, Wang HL, Jiang GB (2015) Evaluation of the in vitro estrogenicity of emerging bisphenol analogs and their respective estrogenic contributions in municipal sewage sludge in China. Chemosphere 124:150–155

    Article  CAS  Google Scholar 

  • Sastre-Serra J, Company MM, Garau I, Oliver J, Roca P (2010) Estrogen down-regulates uncoupling proteins and increase oxidative stress in breast cancer. Free Radical Bio Med 48:506–512

    Article  Google Scholar 

  • Shang Y, Zhang L, Jiang YT, Li Y, Lu P (2014) Airborne quinones induce cytotoxicity and DNA damage in human lung epithelial A549 cells: the role of reactive oxygen species. Chemosphere 100:42–49

    Article  CAS  Google Scholar 

  • Sheng ZC, Zhu BZ (2011) Low concentrations of bisphenol a induce mouse spermatogonial cell proliferation by a protein-coupled recetor 30 and estrogen receptor-alpha. Environ Health Perspect 119:1775–1780

  • Song SJ, Ruan T, Wang T, Liu RZ, Jing GB (2012) Distribution and preliminary exposure assessment of bisphenol AF (BPAF) in various environment matrices around a manufacturing plant in China. Environ Sci Technol 46:13136–13143

    Article  CAS  Google Scholar 

  • Thomas P, Dong J (2006) Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: a potential novel mechanism of endocrine disruption. J Steroid Biochem 102:175–179

    Article  CAS  Google Scholar 

  • Ventura C, Núnez M, Miret N, Lamas DM, Randi A, Venturino A, Rivera E, Cocca C (2012) Differential mechanisms of action are involved in chlorpyrifos effects in estrogen-dependent or –independent breast cancer cells exposed to low or high concentrations of the pesticide. Toxicol Lett 213:184–193

    Article  CAS  Google Scholar 

  • Wei Y, Zhang Z, Liao H, Wu L, Wu X, Zhou D, Xi X, Zhu Y, Feng Y (2012) Nuclear estrogen receptor-mediated Notch signaling and GPR30-mediated PI3K/AKT signaling in the regulation of endometrial cancer proliferation. Oncol Rep 27:504–510

    CAS  Google Scholar 

  • Yang YJ, Guan J, Yin J, Shao B, Li H (2014) Urinary levels of bisphenol analogues in residents living near a manufacturing plant in south China. Chemosphere 112:481–486

    Article  CAS  Google Scholar 

  • Yang YJ, Yin J, Yang Y, Zhou NY, Zhang J, Shao B, Wu YN (2012) Determination of bisphenol AF (BPAF) in tissues, serum, urine and feces of orally dosed rats by ultra-high-pressure liquid chromatography-electrospray tandem mass spectrometry. J Chromatogr B 901:93–97

    Article  CAS  Google Scholar 

  • Yuan L, Dietrich AK, Nardulli AM (2014) 17beta-estradiol alters oxidative stress response protein expression and oxidative damage in the uterus. Mol Cell Endocrinol 382:218–226

    Article  CAS  Google Scholar 

  • Yue W, Yager JD, Wang JP, Jupe ER, Santen RJ (2013) Estrogen receptor dependent and independent mechanisms of breast cancer carcinogenesis. Steroids 78:161–170

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the supports of the National Natural Science Foundation of China (No. 21507078, 41430644, 41373098), the Open Fund of State Key Laboratory of Organic Geochemistry (No. OGL-201410), and the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT13078).

Author information

Authors and Affiliations

  1. Institute of Environmental Pollution and Health, College of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China

    Bingli Lei, Su Sun, Jie Xu, Yingxin Yu, Gang Xu, Minghong Wu & Wei Peng

  2. State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environment Sciences, Beijing, 100012, China

    Chenglian Feng

Authors
  1. Bingli Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Su Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chenglian Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yingxin Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Minghong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wei Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Bingli Lei or Yingxin Yu.

Additional information

Responsible editor: Philippe Garrigues

Electronic supplementary material

Figure 1S

(DOCX 1148 kb).

Figure 2S

(DOCX 931 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lei, B., Sun, S., Xu, J. et al. Low-concentration BPAF- and BPF-induced cell biological effects are mediated by ROS in MCF-7 breast cancer cells. Environ Sci Pollut Res 25, 3200–3208 (2018). https://doi.org/10.1007/s11356-017-9709-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-017-9709-7

Keywords

Search

Navigation