Cancer cell selective probe by mimicking EGCG

Kumazoe, Motofumi; Hiroi, Shun; Tanimoto, Yousuke; Miyakawa, Jyunichi; Yamanouchi, Maasa; Suemasu, Yumi; Yoshitomi, Ren; Murata, Mariko; Fujimura, Yoshinori; Takahashi, Takashi; Tanaka, Hiroshi; Tachibana, Hirofumi

doi:10.1016/j.bbrc.2020.03.021

Cited by 13 publications

(11 citation statements)

References 27 publications

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“…Consistent with their findings, we and another group showed overexpressed 67LR mediated selective toxicity in several types of hematopoietic cancer [21][22][23]. Moreover, we demonstrated that 67LR activated the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS)/cyclic guanosine monophosphate (cGMP) axis [24][25][26][27] as an early molecular event in EGCG-induced cell death. We also demonstrated that EGCG-elicited cGMP upregulation induced acid sphingomyelinase (ASM) activation through phospholipase C/protein kinase C delta systems [28].…”

Section: Introductionsupporting

confidence: 87%

“…Considering the role of FAK/Src in cell mobility and invasion [29,41,42], those mechanisms could be involved in the negative role of 67LR. Moreover, 67LR also acts as a cancer specific death receptor through activation of the cGMP/ASM axis [25][26][27] and inhibits the growth of melanoma through cytoskeletal rearrangement [19,44]. The two different roles of FAK/Src in cell mobility and apoptosis could explain the paradoxical role of 67LR in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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Src Mediates Epigallocatechin-3-O-Gallate-Elicited Acid Sphingomyelinase Activation

et al. 2020

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Epigallocatechin-3-O-gallate (EGCG) is one of the major bioactive compounds known to be present in green tea. We previously reported that EGCG shows selective toxicity through activation of the protein kinase B (Akt)/cyclic guanosine monophosphate (cGMP)/acid sphingomyelinase (ASM) axis via targeting its receptor 67-kDa laminin receptor (67LR), which is overexpressed in cancer. However, little is known about upstream mechanisms of EGCG-elicited ASM activation. In this study we show that the proto-oncogene tyrosine-protein kinase Src, also known as c-src, plays a crucial role in the anticancer effect of EGCG. We showed that EGCG elicits phosphorylation of Src at Tyr 416, a crucial phosphorylation site for its activity, and that the pharmacological inhibition of Src impedes the upstream events in EGCG-induced cell death signaling including upregulation of Akt activity, increase in cGMP levels, and activation of ASM. Moreover, focal adhesion kinase (FAK), which is involved in the phosphorylation of Src, is colocalized with 67LR. EGCG treatment enhanced interaction of FAK and 67LR. Consistent with these findings, pharmacological inhibition of FAK significantly neutralized EGCG-induced upregulation of Akt activity and activation of ASM. Taken together, FAK/Src play crucial roles in the upstream signaling of EGCG.

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Section: Introductionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Src Mediates Epigallocatechin-3-O-Gallate-Elicited Acid Sphingomyelinase Activation

et al. 2020

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“…On the other hand, we have shown that the activation of 67LR signaling induced degranulation-suppressive cytoskeletal modifications, such as actin remodeling based on the inhibition of myosin regulatory light chain phosphorylation and disappearance of membrane ruffling that is morphologically observed in degranulation . Previous studies also showed that EGCG3″Me induced both Akt activation and cGMP production in cancer cells. , The 67LR-mediated Akt phosphorylation activated endothelial nitric oxide synthase, and nitric oxide was generated . Subsequently, this mediator induced the activation of sGC, and cGMP was produced.…”

Section: Resultsmentioning

confidence: 83%

“…11 Previous studies also showed that EGCG3″Me induced both Akt activation and cGMP production in cancer cells. 35,42 The 67LR-mediated Akt phosphorylation activated endothelial nitric oxide synthase, and nitric oxide was generated. 17 Subsequently, this mediator induced the activation of sGC, and cGMP was produced.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Eriodictyol-Amplified 67-kDa Laminin Receptor Signaling Potentiates the Antiallergic Effect of O-Methylated Catechin

et al. 2021

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(−)-Epigallocatechin-3-O-(3-O-methyl) gallate (1, EGCG3″Me), an antiallergic O-methylated catechin, is present in high quantities in the green tea cultivar “Benifuuki” (Camellia sinensis L.). Previous studies have shown that EGCG3″Me inhibited basophil degranulation mediated through the cell-surface 67-kDa laminin receptor (67LR), but the mechanisms are not fully elucidated. This study aimed to investigate the mechanisms underlying the inhibitory effect of EGCG3″Me on IgE/antigen (Ag)-mediated degranulation and the combined effect of EGCG3″Me with eriodictyol (2), a bioactive flavanone. EGCG3″Me inhibited β-hexosaminidase release from the rat basophilic/mast cell line RBL-2H3 stimulated by IgE/Ag and induced acid sphingomyelinase (ASM) activity. This induction was inhibited by anti-67LR antibody treatment. The ASM-specific inhibitor desipramine inhibited EGCG3″Me-induced suppression of degranulation. The soluble guanylate cyclase (sGC) inhibitor NS2028 weakened the potency of EGCG3″Me, and the sGC activator BAY41-2272 suppressed degranulation. The ability of EGCG3″Me to induce ASM activity and inhibit degranulation was amplified by eriodictyol. Furthermore, oral administration of the lemon-peel-derived eriodyctiol-7-O-glucoside (3) potentiated the suppressive effect of EGCG3″Me-rich “Benifuuki” green tea on the IgE/Ag-induced passive cutaneous anaphylaxis (PCA) reaction in BALB/c mice. These results suggest that EGCG3″Me inhibits IgE/Ag-mediated degranulation by inducing the 67LR/sGC/ASM signaling pathway, and eriodictyol amplifies this signaling.

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“…EGCG was a well‐known anti‐tumor ingredient which was extracted from green tea (Hwang et al, 2020). Besides, the mechanisms of the anti‐tumor effects (Wei et al, 2020; Zhang et al, 2020), induction of autophagy‐related apoptosis for example (Chen et al, 2020), were well‐studied in many cancers (Kumazoe et al, 2020; Naujokat & McKee, 2020), including bladder cancer (Dettlaff et al, 2017). However, whether autophagy was involved in its anti‐cancer effect remains undiscovered.…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin‐3‐gallate induces autophagy‐related apoptosis associated with LC3B II and Beclin expression of bladder cancer cells

Yin

Kang

et al. 2021

J. Food Biochem.

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The incidence of bladder cancer in traditional green tea‐consuming countries was dramatically lower than low green tea‐consuming countries. Epigallocatechin‐3‐gallate (EGCG), an active ingredient extracted from green tea, showed effective inhibition of formation and progression of many tumors. However, whether autophagy involved in this tumor‐suppression mechanism of EGCG on bladder cancer was still unclear. In this study, we demonstrated low concentration of EGCG‐induced proliferation inhibition and increased apoptosis in bladder cancer cell lines (5,637 and T24 cells) indicated by the increased expression of apoptosis‐related protein (caspase9, caspase3 and BAX). In addition, low dose of EGCG also regulated autophagy pathway associated protein (LC3B II and Beclin) expression and this autophagy pathway was blocked by PI3K/AKT inhibitor; moreover, knockdown of ATG5 reversed EGCG‐induced apoptosis in 5,637 cells, indicating that EGCG might inhibit the bladder cancer through autophagy pathway. Our findings indicated that EGCG should be considered as a novel therapy for bladder cancer treatment by regulating autophagy pathway. Practical applications Our research proved EGCG from green tea could be used as an effective anti‐tumor ingredient by revealing another mechanism that epigallocatechin‐3‐Gallate inhibited bladder cancer cells via inducing autophagy‐related apoptosis. And green tea could be considered as a kind of tumor‐preventing beverage.

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Cancer cell selective probe by mimicking EGCG

Cited by 13 publications

References 27 publications

Src Mediates Epigallocatechin-3-O-Gallate-Elicited Acid Sphingomyelinase Activation

Src Mediates Epigallocatechin-3-O-Gallate-Elicited Acid Sphingomyelinase Activation

Eriodictyol-Amplified 67-kDa Laminin Receptor Signaling Potentiates the Antiallergic Effect of O-Methylated Catechin

Epigallocatechin‐3‐gallate induces autophagy‐related apoptosis associated with LC3B II and Beclin expression of bladder cancer cells

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