Abstract:
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.
