Nano-chemotherapeutic efficacy of (−) -epigallocatechin 3-gallate mediating apoptosis in A549 cells: Involvement of reactive oxygen species mediated Nrf2/Keap1signaling

Velavan, Bakthavatchalam; Divya, Thomas; Sadagopan, Suresh Kumar Ananda; Sudhandiran, Ganapasam

doi:10.1016/j.bbrc.2018.07.105

Cited by 39 publications

(16 citation statements)

References 22 publications

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“…The involvement of ROS in the execution of cell death is a well‐known phenomenon. ROS are important signaling molecules in various cellular processes such as growth, differentiation, and apoptosis (Velavan, Divya, Sureshkumar, & Sudhandiran, 2018). Most cancer cells undergo oxidative stress due to the increased production of intrinsic ROS (Poornima, Weng, et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Neferine, an alkaloid from lotus seed embryo targets HeLa and SiHa cervical cancer cells via pro‐oxidant anticancer mechanism

Dasari

Bakthavachalam

Chinnapaka

et al. 2020

Phytotherapy Research

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Apoptosis and autophagy are important processes that control cellular homeostasis and have been highlighted as promising targets for novel anticancer drugs. This study aims to investigate the inhibitory effects and mechanisms of Neferine (Nef), an alkaloid from the lotus seed embryos of Nelumbo nucifera (N. nucifera), as a dual inducer of apoptosis and autophagy through the reactive oxygen species (ROS) activation in cervical cancer cells. Nef and N. nucifera extract suppressed the cell viability of HeLa and SiHa cells in a dose‐dependent manner. Importantly, Nef showed minimal toxicity to normal cells. Furthermore, Nef inhibited anchorage‐independent growth, colony formation and migration ability of cervical cancer cells. Nef induces mitochondrial apoptosis by increasing pro‐apoptotic protein bax, cytochrome‐c, cleaved caspase‐3 and caspase‐9, poly‐ADP ribose polymerase (PARP) cleavage, DNA damage (pH2AX) while downregulating Bcl‐2, procaspase‐3 and procaspase‐9, and TCTP. Of note, apoptotic effect by Nef was significantly attenuated in the presence of N‐acetylcysteine (NAC), suggesting pro‐oxidant activity of this compound. Nef also promoted autophagy induction through increasing beclin‐1, atg‐4, atg‐5 and atg‐12, LC‐3 activation, and P62/SQSTM1 as determined by western blot analysis. Collectively, these results demonstrate that Nef is a potent anticancer compound against cervical cancer cells through inducing apoptosis and autophagic pathway involving ROS.

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Section: Discussionmentioning

confidence: 99%

Neferine, an alkaloid from lotus seed embryo targets HeLa and SiHa cervical cancer cells via pro‐oxidant anticancer mechanism

Dasari

Bakthavachalam

Chinnapaka

et al. 2020

Phytotherapy Research

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“…Together with the inhibition of cell proliferation, migration, and angiogenesis, induction of apoptosis is one of the main mechanisms through which EGCG exerts its anti-tumour activity [140,141]. Several studies reported that EGCG is able to affect the expression and function of anti-apoptotic factors (e.g., Bcl-2, Bcl-xl) and to up-regulate pro-apoptotic molecules (e.g., Bax, caspase-3) in several cancer models [58,142,143,144]. However, the mechanisms through which EGCG modulates key cell death regulators are not completely understood.…”

Section: 67-kda Laminin Receptor Signalling Pathwaysmentioning

confidence: 99%

Molecular Targets of Epigallocatechin—Gallate (EGCG): A Special Focus on Signal Transduction and Cancer

et al. 2018

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Green tea is a beverage that is widely consumed worldwide and is believed to exert effects on different diseases, including cancer. The major components of green tea are catechins, a family of polyphenols. Among them, epigallocatechin-gallate (EGCG) is the most abundant and biologically active. EGCG is widely studied for its anti-cancer properties. However, the cellular and molecular mechanisms explaining its action have not been completely understood, yet. EGCG is effective in vivo at micromolar concentrations, suggesting that its action is mediated by interaction with specific targets that are involved in the regulation of crucial steps of cell proliferation, survival, and metastatic spread. Recently, several proteins have been identified as EGCG direct interactors. Among them, the trans-membrane receptor 67LR has been identified as a high affinity EGCG receptor. 67LR is a master regulator of many pathways affecting cell proliferation or apoptosis, also regulating cancer stem cells (CSCs) activity. EGCG was also found to be interacting directly with Pin1, TGFR-II, and metalloproteinases (MMPs) (mainly MMP2 and MMP9), which respectively regulate EGCG-dependent inhibition of NF-kB, epithelial-mesenchimal transaction (EMT) and cellular invasion. EGCG interacts with DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which modulates epigenetic changes. The bulk of this novel knowledge provides information about the mechanisms of action of EGCG and may explain its onco-suppressive function. The identification of crucial signalling pathways that are related to cancer onset and progression whose master regulators interacts with EGCG may disclose intriguing pharmacological targets, and eventually lead to novel combined treatments in which EGCG acts synergistically with known drugs.

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“…Furthermore, EGCG in the circulation is mostly albumin-associated, increasing stability but decreasing bioavailability [37]. Methods to increase bioavailability via nanomedicine and controlled delivery are currently being explored [69, 70].…”

Section: Discussionmentioning

confidence: 99%

Isocitrate dehydrogenase 1-mutated cancers are sensitive to the green tea polyphenol epigallocatechin-3-gallate

et al. 2019

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Background Mutations in isocitrate dehydrogenase 1 ( IDH1 ) occur in various types of cancer and induce metabolic alterations resulting from the neomorphic activity that causes production of D -2-hydroxyglutarate ( D- 2-HG) at the expense of α-ketoglutarate (α-KG) and NADPH. To overcome metabolic stress induced by these alterations, IDH -mutated ( IDH mut ) cancers utilize rescue mechanisms comprising pathways in which glutaminase and glutamate dehydrogenase (GLUD) are involved. We hypothesized that inhibition of glutamate processing with the pleiotropic GLUD-inhibitor epigallocatechin-3-gallate (EGCG) would not only hamper D- 2-HG production, but also decrease NAD(P)H and α-KG synthesis in IDH mut cancers, resulting in increased metabolic stress and increased sensitivity to radiotherapy. Methods We performed 13 C-tracing studies to show that HCT116 colorectal cancer cells with an IDH1 R132H knock-in allele depend more on glutaminolysis than on glycolysis for the production of D -2-HG. We treated HCT116 cells, HCT116- IDH1 R132H cells, and HT1080 cells (carrying an IDH1 R132C mutation) with EGCG and evaluated D- 2-HG production, cell proliferation rates, and sensitivity to radiotherapy. Results Significant amounts of 13 C from glutamate accumulate in D- 2-HG in HCT116- IDH1 wt/R132H but not in HCT116- IDH1 wt/wt . Preventing glutamate processing in HCT116- IDH1 wt/R132H cells with EGCG resulted in reduction of D- 2-HG production. In addition, EGCG treatment decreased proliferation rates of IDH1 mut cells and at high doses sensitized cancer cells to ionizing radiation. Effects of EGCG in IDH-mutated cell lines were diminished by treatment with the IDH1 mut inhibitor AGI-5198. Conclusions This work shows that glutamate can be directly processed into D- 2-HG and that reduction of glutamatolysis may be an effective and promising new treatment option for IDH mut cancers. Electronic supplementary material The online version of this article (10.1186/s40170-019-0198-7) contains supplementary material, which is available to authorized users.

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Nano-chemotherapeutic efficacy of (−) -epigallocatechin 3-gallate mediating apoptosis in A549 cells: Involvement of reactive oxygen species mediated Nrf2/Keap1signaling

Cited by 39 publications

References 22 publications

Neferine, an alkaloid from lotus seed embryo targets HeLa and SiHa cervical cancer cells via pro‐oxidant anticancer mechanism

Neferine, an alkaloid from lotus seed embryo targets HeLa and SiHa cervical cancer cells via pro‐oxidant anticancer mechanism

Molecular Targets of Epigallocatechin—Gallate (EGCG): A Special Focus on Signal Transduction and Cancer

Isocitrate dehydrogenase 1-mutated cancers are sensitive to the green tea polyphenol epigallocatechin-3-gallate

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Nano-chemotherapeutic efficacy of (−) -epigallocatechin 3-gallate mediating apoptosis in A549 cells: Involvement of reactive oxygen species mediated Nrf2/Keap1signaling

Cited by 39 publications

References 22 publications

Neferine, an alkaloid from lotus seed embryo targets HeLa and SiHa cervical cancer cells via pro‐oxidant anticancer mechanism

Neferine, an alkaloid from lotus seed embryo targets HeLa and SiHa cervical cancer cells via pro‐oxidant anticancer mechanism

Molecular Targets of Epigallocatechin—Gallate (EGCG): A Special Focus on Signal Transduction and Cancer

Isocitrate dehydrogenase 1-mutated cancers are sensitive to the green tea polyphenol epigallocatechin-3-gallate

Contact Info

Product

Resources

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Nano-chemotherapeutic efficacy of (−) -epigallocatechin 3-gallate mediating apoptosis in A549 cells: Involvement of reactive oxygen species mediated Nrf2/Keap1signaling