Tea Polyphenols Induce Apoptosis Through Mitochondrial Pathway and by Inhibiting Nuclear Factor-κB and Akt Activation in Human Cervical Cancer Cells

Abstract

Phytochemicals present in tea, particularly polyphenols, have anticancer properties against several cancer types. However, studies elucidating the role and the mechanism(s) of action of tea polyphenols in cervical cancer are sparse. In this study, we investigated the mechanism of antiproliferative and apoptotic actions exerted by tea polyphenols on human papilloma virus-18-positive HeLa cervical cancer cells. Treatment of green tea polyphenol (-)-epigallocatechin gallate (EGCG) and black tea polyphenol theaflavins (TF) in HeLa cells showed a marked concentration- and time-dependent inhibition of proliferation and induced sub-G1 phase in a dose-dependent manner after 24 h. There was an attenuation of mitochondrial membrane potential with the increase of reactive oxygen species generation, p53 expression, Bax/Bcl-2 ratio, cytochrome-c release, and cleavage of procaspase-3 and -9 and poly(ADP-ribose)-polymerase, indicating the participation of a mitochondria related mechanism. In addition, EGCG as well as TF inhibited activation of Akt and nuclear factor-kappaB (NF-kappaB) via blocking phosphorylation and subsequent degradation of inhibitor of kappaBalpha and kappaBbeta subunits, thereby downregulating cyclooxygenase-2. Additionally, the protein level of cyclin D1, a transcriptional target of NF-kappaB, was also reduced significantly. Thus, we can conclude that tea polyphenols inhibit the growth of cervical cancer cells by inducing apoptosis and regulating NF-kappaB and Akt.

PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma

“…43 Excessive generation of ROS and a decline in ΔΨm has been documented in cancer cells treated with tea polyphenols. 4,6,7 Notably, in our study, these results were also observed at a low concentration of TF/EGCG-NPs (1/20th, 1/10th and 1/5th of the respective bulk IC 50 dose), again confirming the marked dose advantage achieved when TF/EGCG is delivered using a NP formulation.…”

“…35 We have already documented the potential of tea polyphenols in inhibition of NF-κB activity. 6,7 In our present study, we noted the significant effect of a low concentration of TF/EGCG-NPs on chemosensitivity to CDDP (IC 20 dose) via inhibition of NF-κB and its corresponding gene. It was found that low doses of TF/EGCG-loaded NPs (1/20th, 1/10th, and 1/5th of the respective bulk IC 50 dose) suppressed NF-κB activation more efficiently in combination with CDDP than did the bulk TF/EGCG (IC 50 dose).…”

“…34 CDDP is reported to enhance the activity of NF-κB, 35 and tea polyphenols are reported to suppress the action of NF-κB. 7 The test concentration of CDDP was found to enhance activation of NF-κB in a time-dependent manner (data not shown). To determine whether being loaded into PLGA-NPs enhances the ability of TF/EGCG to suppress CDDP-induced NF-κB, the cells were incubated with different concentrations of bulk TF/EGCG or TF/EGCG-loaded NPs for 24 hours alone or in combination with a selected dose of CDDP.…”

“…Catechins found in both black tea and green tea have been shown to suppress several key pathways linked to oncogenesis, including those involved in cell survival, proliferation, and invasion, along with angiogenesis. [6][7][8][9][10] Earlier reports from our laboratory have established that tea polyphenols have excellent potential to chemosensitize cancer cells towards chemotherapeutic drugs like CDDP. 4,11 Further, combined treatment with tea polyphenols and CDDP synergistically induced apoptosis by activation of caspase-8 and caspase-9 and overexpression of p53.…”

Triptolide Inhibits Proliferation and Induces Apoptosis of Human Melanoma A375 Cells

“…Researches have shown that disregulation of NF-κB transcription machinery is one of the factors thought to be common early events in malignant tumor progression (Meng et al, 2012). Thus, it is becoming increasingly clear that compounds that block NF-κB activation could be highly useful for the treatment of cancers (Singh et al, 2011). Bcl-2 and Bcl-X L are members of the Bcl-2 family regulated by NF-κB.…”