EGCG has inhibitory effect on a variety of cancers by inducing apoptosis and cell cycle arrest or inhibiting angiogenesis and metastasis. EGCG has been found to induce apoptosis in salivary gland carcinoma cells. But the potential anti-invasive effect of EGCG in salivary gland cancer has not been studied yet. The aim of this study is to evaluate the effect of EGCG on salivary gland adenocarcinoma SGT cell adhesion and migration to Type I collagen treatment. Western blot, adhesion and migration assay were performed to evaluate the impacts of EGCG on the expression of MMP-2/-9 and its upstream signaling molecules after treatment of type I collagen. SGT cell adhesion to type I collagen is significantly suppressed by EGCG. EGCG decreased expression of β1 integrin, phosphorylation of FAK, MMP-2/-9 compared with type I collagen treatment. In addition, EGCG inhibited the migration of SGT cells treated with type I collagen. These results suggest that EGCG could effectively inhibit the invasion and migration of human SGT cells by downregulating the expression of β1 integrin and MMP-2/-9 and phosphorylation of FAK, Akt, and Erk. Adhesion and migration to type I collagen of SGT cells can be influenced through EGCG.

Epigallocatechin-3-gallate (EGCG) and theaflavins (TF) are polyphenols included in green and black teas, respectively. Both green and black teas have been studied for their potential health benefits for cancer. Hypoxia-inducible factor (HIF) has been implicated multiple physiological and pathophysiological pathways, particularly, oncogenesis. But, the molecular pathways that govern the cell response to EGCG are not fully elucidated. The present study investigated the intracellular mechanism in oral squamous cell carcinoma (OSCC) cells treated with EGCG, focusing on HIF-1 expression and its effect on epithelial phenotype. EGCG decreased phosphorylated Raf-1 protein in YD 8 OSCC cell, but B-raf protein was not affected at all by EGCG and TF. In addition, we here found that EGCG regulated HIF-1α expression independent of Raf-1 protein. Taken together with our previous result, the result imply that EGCG is attributed to the HIF-1α expression via Raf/MEK/ERK pathway, and the HIF-1α expression is associated with the change of epithelial phenotype in OSCC cell.

Adherent cells, such as those found in epithelial tissues, must be physically associated with extracellular matrix (ECM)components to survive. Though stimulation by growth factors is an essential factor in cell survival, normal cells also requires cell adhesion to ECM proteins. The cessation of these anchorage-mediated signals seems to be a common mechanism to physiolog ically t erminate t he l ife cycle of t hese c ells b y apoptosis. This form o f cell death has been termed anoikis.In cancer, resistance to anoikis of cancer cell is important in invasion and metastasis. The present study investigated the intracellular mechanism involved in anoikis, especially in cells treated with epigallocatechin- 3-gallate(EGCG). To induce anoikis, cell culture plates were coated with 10 ㎍/ml poly-HEMA. A549 lung adenocarcinoma cells were grown in RPMI 1640 medium with/without 10% fetal bovine serum, and then cells were replated on cell culture dishes coated with poly-HEMA in the presence or absence of serum. On the other hand, EGFR inhibitor, PI3K inhibitor, and EGCG were treated to the anoikis status cells, in order to evaluate the factors of anoikis. The result revealed that growth factors or loss of adhesion can increase phosphorylate Akt. In addition, lack of cell adhesion fails to activate pro-apoptotic factors directly. Activity of Erk kinase depends on not only EGFR signaling but also cell adhesion. Akt activation is mainly affected by EGCG whereas Raf-1 activation is controlled by the presence of cell contact. In addition, EGCG increased the level of NFkB, whereas phophroylated PTEN and total PTEN were not different. In this report,increase of NFkB was correlated with Akt phosphorylation, suggesting that EGCG can protect cells from detachment–induced cell death through Akt activation and subsequent NFkB

Green tea, derived from the plant Camellia sinensis, is one of the most common beverages consumed worldwide. Epigallocatechin-3-gallate (EGCG) is the most abundant and bioactive polyphenolic constituent in green tea. Understanding how intracellular signaling pathways respond to EGCG may provide a clue to the difference of cell responses and basis for usefulness of EGCG as a chemopreventive and/or chemotherapeutic agent. In the present study, we tried to check whether EGCG could be a useful agent in chemotherapeutic treatment of oral squamous carcinoma. Furthermore, we investigated which signaling pathway is involved in biologic activities of EGCG. EGCG induced the cell death of oral squamous carcinoma cells. Furthermore, it increased phosphorylation of Akt in serum-strarved oral squamous carcinoma cells. But, initial increase of Akt activation did not affect cell survival. Activities of Raf-1 and Erk showed inconsistent response to EGCG treatment, but Erk phosphorylation is consistent with Raf-1 activity in YD 10B cells. These changes of Raf-1 and Erk activity in EGCG treated cells were different depending on cell line type. Supposedly, the difference of cell component may affect the Raf-1 and Erk reactivity to EGCG treatment. Akt activation by EGCG is independent on activities of PDK1 and PTEN, and expression of bax and bcl-2 proteins were not changed by EGCG treatment. Therefore, EGCG treatment did not induce the apoptosis of YD 10B cell. On the other hand, vascular adhesion molecule (VCAM) was decreased by EGCG treatment, so it is possible that decrease of VCAM can play certain role in survival and/or cell death in EGCG treated cells

The major component of green tea is (-)-epigallocatechin-3-gallate(EGCG) which accounts for 5080% of catechin, representing 200300 mg in a brewed cup of green tea. EGCG has been known to possess growth inhibitory and pro-apoptotic effect on human cancer cell lines such as prostate, bladder and breast cancers. In contrast, several studies have suggested that EGCG could promote cell proliferation and/or survival instead of pro-apoptotic effect. Understanding how intracellular signaling pathways respond to EGCG may provide a clue to the difference of cell responses and basis for usefulness of EGCG as a chemopreventive and/or chemotherapeutic agent. To better understand the mechanisms responsible for the chemopreventive efficacy of EGCG, the authors tried to identify the key molecules that contributes to Akt activation and can inhibit this activation. In the present study, EGCG increased Akt phosphorylation, an activeform of Akt and negatively affect on direct upstream molecules of Akt including PTEN and EGFR, though Akt phosphorylation was increased.

( - ) -epigall ocatechin - 3 -ga ll ate(EGCG) 는 녹차에서 추출되는 주된 성분으로 항산화. 세포 증식 억제 및 세 포 자멸사를 유도힌다 고 알려져 있다‘ 현 재 끼지의 여러 연구에 의하띤 EGCG는 세 포 성장을 억제하고 나아가서는 apoptoS1S까지도 유발한다. 한편 일부 연구는 EGCG가 오히려 apo ptosi s를 억 제 하고， 세 포 증식을 촉진한다고 보고하고 있다. 저자들은 EGCG가 이러한 상반된 효과틀을 보이게 되 는 기전과 그에 관련된 물질들을 파악하고지 하였다， EGCG를 세포에 처리시 초기에는 세포 생존에 관여힌다고 알려진 인 산화된 Akt 단백이 증가함이 관찰되었다 그 외에도 인산화된 Erk 단백 등의 증가로 EGCG가 세포 생존을 지속시키 는 역할을 하고 있음을 알 수 있었다‘ 이러한 현상은 COS7 과 A549 세 포 에서 관찰되었으며 Hela 세포에서는 관찰되지 않아 세 포외부에서 EGCG가 결합하게 되 는 물질 혹은 세 포내 물질 등의 차이에 의해 세 포 미다 EGCG에 대한 반응이 다른 것으로 추측된다 24시간 이상 처리된 경우 ECCG가 세 포 생존에 관린된 인자들을 감소시키는 것으로 보아 EGCG에 처음에는 세 포 생존을 유도하지만 장시간 처리 시 세 포 증식 및 생존을 억제하는 물질 임 을 확인하였다.

In t his study, we tried to identify the key elements that respond to EGCG t reatment and its role in cell survival 0 1' apop tosis by EGCG. focusing on Akt pathway and Raf-MEK-ERK pathways. Cells were serum starved for 16 h and then treated with (-) -epiga llocatechin-3-gallate. To cletermine which pathway is related to effects of EGCG on cell s, the levels of phosphorylated Akt(pAkt) and Erk (pErk) were a nalyzed by immunoblotting. A549 cell s showed the increase of pAkt in response to EGCG‘ whereas Hela cells exhi bited no difference in the levels of pAkt by EGCG treatment Phos phorylation of Akt over initial basal levels became evident a fter 1 h of EGCG treatment and peaked at 3 h pErk was also increased by EGCG in Hela cells as well as in A549 cells To determine th e effect of EGCG on growth of cells‘ A549 cells were treated wi th vari 。u s concentrations of EGCG (from 10 μ M to 300 μ M) for 3 h. Cell growth was examined by MTI assay. The resulting growth curves of A549 cell s showed that EGCG promotecl cell prolifera tion in a close-dependent manner at early phase. When cells were t rea ted with EGCG for 24 h. pAkt and pErk expressions were significantly i띠1ibited ， even at 10 μ M B-raf ex pression was also clecreased in a close-dependent manner. In teresti ngly. the presence of serum weakened t his inhibitory effect of EGCG on the ex pression of survival facto rs. Our study inrucates that EGCG stimulates cell survival of A549 cells through thc PI3K/AKT pathway. though it fina lly be haves like a suppressive agent on cell su rvival