Epigallocathechin gallate, polyphenol present in green tea, inhibits stem-like characteristics and epithelial-mesenchymal transition in nasopharyngeal cancer cell lines

Abstract

BackgroundPrevious studies have demonstrated that the consumption of green tea inhibits the growth of various cancers. Most cancers are believed to be initiated from and maintained by a small population of cancer stem-like cells (CSC) or tumor-initiating cells (TIC) that are responsible for tumor relapse and chemotherapeutic resistance. Although epigallocathechin gallate (EGCG), the most abundant catechin in green tea, has been reported to induce growth inhibition and apoptosis in some cancer cells, its effect on CSC is undefined. In this study, we enriched CSC by the sphere formation, and provided an efficient model for further experiments. Using this method, we examined the effects of EGCG regulating the nasopharyngeal carcinoma (NPC) CSC and attempted to elucidate the possible mechanisms.MethodsNPC TW01 and TW06 cell lines were enriched by sphere formation and characterized their phenotypical properties, such as invasion capacity, epithelial-mesenchymal transition (EMT) and gene expression were analyzed by quantitative real-time reverse transcription polymerase chain reaction (q-RT-PCR). EGCG-induced growth inhibition in the parental and sphere-derived cells was determined by MTT and bromodeoxyuridine (BrdU) assay. EGCG-induced apoptosis was analyzed by flow cytometry with Annexin V and PI staining. The effects of EGCG on sphere-derived cell tumorigenicity, migration and invasion were determined by soft agar assay, wound healing, and cell invasion assay. The alternation of protein expression regulated by EGCG on these sphere-derived cells was assessed by immunofluorescence staining and western blot.ResultsNPC sphere-derived cells grown in serum-free non-adherent culture showed increased expression of stem cell markers and EMT markers compared to parental cells grown in conventional culture. Although EGCG induced growth inhibition and apoptosis in the parental cells in a dose-dependent manner, it was not as effective against spheres. However, EGCG potently inhibited sphere formation and can eliminate the stem cell characteristics of NPC and inhibit the epithelial-mesenchymal transition (EMT) signatures.ConclusionsOverall, these findings show that NPC cells with sphere formations possess the properties of CSC. Using this model, we found that EGCG regulated NPC CSC, their self-renewal capacity, and inhibited their invasive characteristics. It supports the pivotal role of EGCG as a dietary compound targeting NPC and may decrease recurrence and metastasis in nasopharyngeal carcinoma cells.

Pterostilbene inhibits triple-negative breast cancer metastasis via inducing microRNA-205 expression and negatively modulates epithelial-to-mesenchymal transition

“…Therefore, we focused on evaluating the mechanisms underlying the anti-invasive effects of pterostilbene at concentrations no greater than 10 μM. Recent studies have identified many diet-derived, natural products as inhibitors of EMT, including garlic-derived chemicals [20], the soy constituent genistein and green tea polyphenols [21]. In our study, we found that, after treatment with low-dose pterostilbene (10 μM) for 24 h, MDA-MB-231 cells displayed morphological alterations from the mesenchymal phenotype to the epithelial phenotype and possessed an epithelial-like morphology.…”

Ovarian cancer: Concept of pathogenesis and principles of therapy

“…К настоящему моменту всесторонне изучена и подробно описана мультитаргетная противоопухолевая активность I3C, DIM и EGCG в отношении опухолей различного происхождения [17][18][19], в том числе и РЯ [20][21][22], а так-же обнаружена способность DIM [23,24] и EGCG [25,26] …”

“…Недавно было показано, что антиинвазивные и анти-метастатические свойства DIM in vitro и in vivo обуслов-лены подавлением экспрессии ключевых сигнальных бел-ков, опосредующих процесс эпителиально-мезенхималь-ного перехода (ЕМТ) опухолевых клеток [25]. Известно, что в результате обратимого процесса ЕМТ ОСК, вместе с измененной морфологией, вследствие перепрограмми-рования генотипа приобретают инвазивные свойства и метастатическую активность.…”

“…Кроме того, достоверно доказана способность ука-занных веществ подавлять асептическое хроническое воспаление со всеми сопровождающими его биологиче-скими процессами (патологический неоангиогенез, ги-перпролиферация, снижение иммунной функции, гене-тическая нестабильность) [8,27], а также наличие у них всех видов эпигенетической противоопухолевой актив-ности [25].…”

Cancer Chemoprevention by Traditional Chinese Herbal Medicine and Dietary Phytochemicals: Targeting Nrf2-Mediated Oxidative Stress/Anti-Inflammatory Responses, Epigenetics, and Cancer Stem Cells

“…[137] EGCG inhibits the self-renewing capacity of human prostate cancer cell lines (PC-3 and LNCaP) containing a small population of CSCs presenting CD44 + CD133 + . Furthermore, EGCG also inhibits the self-renewing capacity of CD44 + α2β1+CD133 + CSCs isolated from human primary prostate tumors, as measured by spheroid formation in suspension.…”