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Molecules 2018, 23(4), 930; https://doi.org/10.3390/molecules23040930

Chemoresistance to Cancer Treatment: Benzo-α-Pyrene as Friend or Foe?

1
International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Wernher and Beit Building (South), University of Cape Town Medical Campus, Anzio Road, Observatory 7925, Cape Town, South Africa
2
Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa
3
Pharmacogenomics and Drug Metabolism Group, Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa
4
Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 3 April 2018 / Revised: 13 April 2018 / Accepted: 15 April 2018 / Published: 17 April 2018
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Abstract

Background: Environmental pollution such as exposure to pro-carcinogens including benzo-α-pyrene is becoming a major problem globally. Moreover, the effects of benzo-α-pyrene (BaP) on drug pharmacokinetics, pharmacodynamics, and drug resistance warrant further investigation, especially in cancer outpatient chemotherapy where exposure to environmental pollutants might occur. Method: We report here on the effects of benzo-α-pyrene on esophageal cancer cells in vitro, alone, or in combination with chemotherapeutic drugs cisplatin, 5-flurouracil, or paclitaxel. As the study endpoints, we employed expression of proteins involved in cell proliferation, drug metabolism, apoptosis, cell cycle analysis, colony formation, migration, and signaling cascades in the WHCO1 esophageal cancer cell line after 24 h of treatment. Results: Benzo-α-pyrene had no significant effect on WHCO1 cancer cell proliferation but reversed the effect of chemotherapeutic drugs by reducing drug-induced cell death and apoptosis by 30–40% compared to drug-treated cells. The three drugs significantly reduced WHCO1 cell migration by 40–50% compared to control and BaP-treated cells. Combined exposure to drugs was associated with significantly increased apoptosis and reduced colony formation. Evaluation of survival signaling cascades showed that although the MEK-ERK and Akt pathways were activated in the presence of drugs, BaP was a stronger activator of the MEK-ERK and Akt pathways than the drugs. Conclusion: The present study suggest that BaP can reverse the effects of drugs on cancer cells via the activation of survival signaling pathways and upregulation of anti-apoptotic proteins such as Bcl-2 and Bcl-xL. Our data show that BaP contribute to the development of chemoresistant cancer cells. View Full-Text
Keywords: environmental pollution; benzo-α-pyrene; procarcinogen; esophageal cancer; cisplatin; 5-fluorouracil; paclitaxel; chemoresistance; drug metabolizing enzymes; apoptosis environmental pollution; benzo-α-pyrene; procarcinogen; esophageal cancer; cisplatin; 5-fluorouracil; paclitaxel; chemoresistance; drug metabolizing enzymes; apoptosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Dzobo, K.; Hassen, N.; Senthebane, D.A.; Thomford, N.E.; Rowe, A.; Shipanga, H.; Wonkam, A.; Parker, M.I.; Mowla, S.; Dandara, C. Chemoresistance to Cancer Treatment: Benzo-α-Pyrene as Friend or Foe? Molecules 2018, 23, 930.

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