(−)-Epigallocatechin-3-gallate derivatives combined with cisplatin exhibit synergistic inhibitory effects on non-small-cell lung cancer cells

Abstract

Background Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The inhibition of epidermal growth factor receptor (EGFR) signaling by tyrosine kinase inhibitors or monoclonal antibodies plays a key role in NSCLC treatment. Unfortunately, these treatment strategies are limited by eventual resistance and cell lines with differential EGFR status. Therefore, new therapeutic strategies for NSCLC are urgently required. Methods To improve the stability and absorption of (−)-epigallocatechin-3-gallate (EGCG), we synthesized a series of EGCG derivatives. The antitumor activities of EGCG derivatives with or without cisplatin were investigated in vitro and vivo. Cell proliferation, cell cycle distribution and apoptosis were measured in NSCLC cell lines and in vivo in a NCI-H441 xenograft model. Results We found that the EGCG derivatives inhibited cell viability and colony formation, caused cell cycle redistribution, and induced apoptosis. More importantly, the combination of the EGCG derivative and cisplatin led to increased growth inhibition, caused cell cycle redistribution, and enhanced the apoptosis rate compared to either compound alone. Consistent with the experiments in vitro, EGCG derivatives plus cisplatin significantly reduced tumor growth. Conclusions The combination treatment was found to inhibit the EGFR signaling pathway and decrease the expression of p-EGFR, p-AKT, and p-ERK in vitro and vivo. Our results suggest that compound 3 is a novel potential compound for NSCLC patients.

PTEN/AKT/mTOR signaling mediates anticancer effects of epigallocatechin‑3‑gallate in ovarian cancer

“…EGCG exerts its anticancer activity by suppressing cell proliferation, migration and invasion, and by inducing apoptosis in lung cancer cells (8)(9)(10)(11). A number of studies on the anticancer activity of EGCG focus on lung cancer cells (12)(13)(14)(15)(16); however, few studies (17,18) focus on ovarian cancer cells.…”

Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells

“…Furthermore, EGCG induced apoptosis and cell cycle arrest in ovarian cancer cell lines, inhibiting cancer cell growth in vitro [143,144]. Derivatives of EGCG induced apoptosis and inhibited proliferation of non-small-lung-cancer cell lines, especially in combination with the chemotherapeutic cisplatin [106]. EGCG has additionally shown synergistic activity with other anti-cancer treatments, such as tamoxifen (hormone therapy) and nonsteroidal anti-inflammatory drugs (NSAIDs, i.e., cyclooxygenase-2 (COX-2) inhibitors) [145].…”

“…Natural compounds have been investigated for their effects on numerous cancers, including gynaecological malignancies [79], glioblastoma [102], pancreatic cancer [103], breast cancer [104,105], lung cancer [106], prostate cancer [107], colorectal cancer [108,109] and melanoma/skin cancers [110][111][112]. Compounds are mainly selected for their anti-inflammatory properties although evidence has now been obtained that numerous compounds may induce direct killing of cancer cells, i.e., by apoptosis, but also because they can mediate cellular mechanisms and signalling pathways [113].…”

Syntheses and Anticancer Activities of Novel Glucosylated (-)-Epigallocatechin-3-Gallate Derivatives Linked via Triazole Rings

“…And O-alkylated EGCG analogues 8 and 9 were prepared in 30%-45% yields by reacting [24,27]. Finally, compounds 10 and 11 were treated with potassium hydroxide (KOH) solution (dissolved in CH 3 OH) in CH 3 OH at 0 ºC for 72 h to yield triazole-linked glucose-EGCG derivatives 12 and with 52% to 55% yields [28].…”