Tea polyphenols enhance cisplatin chemosensitivity in cervical cancer cells via induction of apoptosis

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Abstract

Aim

Constitutive activation of nuclear factor-kappaB (NF-κB) and Akt has been implicated in chemoresistance as well as inhibition of apoptosis to cisplatin (CDDP), therefore, we examined whether (−) epigallocateocatechin-3-gallate (EGCG) or theaflavins (TF) could sensitize human cancer cells to CDDP via induction of apoptosis mediated by the inactivation of NF-κB and Akt signaling.

Main methods

Human cervical cancer cells (HeLa and SiHa cells) were treated with EGCG or TF and CDDP alone and with their combinations, further their effects on cell viability were evaluated. Western blotting was used for examining the apoptotic signaling proteins and inhibition of NF-κB activation. Levels of reactive oxygen species (ROS) production and mitochondria membrane potential (ΔΨm) were examined by flow cytometry.

Key findings

The combined treatment of EGCG or TF with CDDP elicited significant inhibition of cell growth in comparison to either of them in both cell lines (p < 0.05). Combinatorial treatment of both compounds potentially induced apoptosis by inhibiting the activation of Akt and NF-κB through blocking phosphorylation of inhibitor kappa Bα. These combinations acted in concert to induce increase in ROS level, release of cytochrome-c and expression of p53 and Bax, with decrease in cellular glutathione contents, ΔΨm, and Bcl-2 expression, thereby eventually resulting in the activation of caspases, poly(ADP)ribose polymerase cleavage and apoptosis of cancer cells.

Significance

Study suggests that both EGCG and TF chemosensitize the cervical cancer cells to CDDP-induced growth inhibition and apoptosis. By these combinations ∽ 4 folds increase in CDDP induced-apoptosis with dose advantage of ∽ 3 times could be achieved.

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