New piperidine derivative <scp>DTPEP</scp> acts as dual‐acting anti‐breast cancer agent by targeting <scp>ER</scp>α and downregulating <scp>PI</scp>3K/Akt‐<scp>PKC</scp>α leading to caspase‐dependent apoptosis

Arun, Ashutosh; Ansari, Mohd. Imran; Popli, Pooja; Jaiswal, Swati; Mishra, Anand; Dwivedi, Anila; Hussain, Mohd Kamil; Konwar, Rituraj

doi:10.1111/cpr.12501

Cited by 17 publications

(20 citation statements)

References 51 publications

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“…Thus, PI3K/Akt pathway‐related transduction, including its mechanisms of activation, signal‐transducing molecules and effects on gene expression, contributes to tumorigenesis. Abnormal activation of the PI3k/AKT pathway is observed in numerous solid tumours, including BC, and this pathway controls a series of cellular processes, including cell proliferation, cell cycle, apoptosis, autophagy and cell migration. For example, miR‐613 acts as an upstream regulator that disturbs the interaction between YAP and WBP2, influencing the activity of the EGFR/PI3K pathway in triple‐negative BC cells .…”

Section: Discussionmentioning

confidence: 99%

PLCA8 suppresses breast cancer apoptosis by activating the PI3k/AKT/NF‐κB pathway

Mao

Chen

Jia

et al. 2019

J Cellular Molecular Medi

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The cysteine‐rich lysosomal protein placenta‐specific 8 (PLAC8), also called onzin, has been shown to be involved in many types of cancers, and its role is highly dependent on cellular and physiological contexts. However, the precise function of PLAC8 in breast cancer (BC) progression remains unclear. In this study, we investigated both the clinical significance and biological functions of PLAC8 in BC progression. First, high PLAC8 expression was observed in primary BC tissues compared with adjacent normal tissues through immunohistochemistry analysis. The results of in vitro and in vivo assays further confirmed that PLAC8 overexpression promotes cell proliferation and suppress BC cell apoptosis, whereas PLAC8 silencing has the opposite effect. In addition, the forced expression of PLAC8 greatly induces cell migration, partially by affecting the EMT‐related genes, including down‐regulating E‐cadherin expression and facilitating vimentin expression. Further mechanistic analysis confirmed that PLAC8 contributes to cell proliferation and suppresses cell apoptosis in BC by activating the PI3K/AKT/NF‐κB pathway. The results of our study provide new insights into an oncogenic role of PLAC8 and reveal a novel PLAC8/ PI3K/AKT/NF‐κB pathway as a potential therapeutic target for BC.

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Section: Discussionmentioning

confidence: 99%

PLCA8 suppresses breast cancer apoptosis by activating the PI3k/AKT/NF‐κB pathway

Mao

Chen

Jia

et al. 2019

J Cellular Molecular Medi

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“…70,72 Targeting ERα reportedly causes changes in the expression of components of the PI3K/AKTprotein kinase Cα signaling pathway, resulting in cell apoptosis. 73 Also, the activation of ERα results in increased expression of the PI3K/AKT/NF-κB signaling pathway, leading to tumor invasion and metastasis in breast cancer. 74 As discussed above, membrane ERα is linked to G proteins, transmitting signals from the outside to the inside of the cell.…”

Section: Erα and Signaling Pathwaysmentioning

confidence: 99%

“…In hormone-related cancers, such as breast, endometrial and ovarian cancers, ERα expression contributes to disease progression mostly by regulating the PI3K/AKT signaling pathway. 69,73 Emerging evidence shows that ERα is also crucial to the progression of prostate cancer. 91 Overexpression of ERα in prostate cancer is strongly associated with adverse survival outcomes.…”

Section: Erα and Cancermentioning

confidence: 99%

<p>ERα, A Key Target for Cancer Therapy: A Review</p>

Liu

Yao

2020

OTT

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Estrogen receptor α (ERα) is closely associated with both hormone-dependent and hormone-independent tumors, and it is also essential for the development of these cancers. The functions of ERα are bi-faceted; it can contribute to cancer progression as well as cancer inhibition. Therefore, understanding ERα is vital for the treatment of those cancers that are closely associated with its expression. Here, we will elaborate on ERα based on its structure, localization, activation, modification, and mutation. Also, we will look at coactivators of ERα, elucidate the signaling pathway activated by ERα, and identify cancers related to its activation. A comprehensive understanding of ERα could help us to find new ways to treat cancers.

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“…It also down‐regulated PI3K and Akt expression as well as altered the downstream EMT markers such as E‐cadherin, N‐cadherin, vimentin and Snail . Apoptosis plays a vital role in the progression of multiple cancers and basically activated by a mitochondria‐induced intrinsic or a death receptor‐induced extrinsic pathway, both of which are correlated with mitochondria and Bcl‐2 family anti‐apoptotic proteins . Another two studies on HCT‐116 cells investigated the underlying mechanism of coptisine's anti‐apoptotic effect characterized by affecting diverse apoptosis‐associated targets including ROS, Bcl‐2/‐XL, Bid, Bax, cytochrome c, Apaf‐a, AIF, XIAP, caspase‐3 and caspase‐9.…”

Section: Anti‐cancer Propertymentioning

confidence: 99%

“…25 Apoptosis plays a vital role in the progression of multiple cancers and basically activated by a mitochondria-induced intrinsic or a death receptorinduced extrinsic pathway, both of which are correlated with mitochondria and Bcl-2 family anti-apoptotic proteins. [26][27][28] Another two studies on HCT-116 cells investigated the underlying mechanism of F I G U R E 2 Non-liner relationships between CC alkaloid dosages and plasma concentration (Cmax). There is an obvious process of limitation, and the bioavailability decreased along with the elevated dosage coptisine's anti-apoptotic effect characterized by affecting diverse apoptosis-associated targets including ROS, Bcl-2/-XL, Bid, Bax, cytochrome c, Apaf-a, AIF, XIAP, caspase-3 and caspase-9.…”

Section: Anti -C An Cer Propert Ymentioning

confidence: 99%

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

Luo

Deng

et al. 2019

J Cellular Molecular Medi

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Coptisine is a natural small‐molecular compound extracted from Coptis chinensis (CC) with a history of using for thousands of years. This work aimed at summarizing coptisine's activity and providing advice for its clinical use. We analysed the online papers in the database of SciFinder, Web of Science, PubMed, Google scholar and CNKI by setting keywords as ‘coptisine’ in combination of ‘each pivotal pathway target’. Based on the existing literatures, we find (a) coptisine exerted potential to be an anti‐cancer, anti‐inflammatory, CAD ameliorating or anti‐bacterial drug through regulating the signalling transduction of pathways such as NF‐κB, MAPK, PI3K/Akt, NLRP3 inflammasome, RANKL/RANK and Beclin 1/Sirt1. However, we also (b) observe that the plasma concentration of coptisine demonstrates obvious non‐liner relationship with dosage, and even the highest dosage used in animal study actually cannot reach the minimum concentration level used in cell experiments owing to the poor absorption and low availability of coptisine. We conclude (a) further investigations can focus on coptisine's effect on caspase‐1‐involved inflammasome assembling and pyroptosis activation, as well as autophagy. (b) Under circumstance of promoting coptisine availability by pursuing nano‐ or microrods strategies or applying salt‐forming process to coptisine, can it be introduced to clinical trial.

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New piperidine derivative DTPEP acts as dual‐acting anti‐breast cancer agent by targeting ERα and downregulating PI3K/Akt‐PKCα leading to caspase‐dependent apoptosis

Abstract: We identified a new dual-acting anti-breast cancer molecules as a proof of concept which is capable of targeting both ER-positive and ER-negative breast cancer.

Cited by 17 publications

References 51 publications

PLCA8 suppresses breast cancer apoptosis by activating the PI3k/AKT/NF‐κB pathway

PLCA8 suppresses breast cancer apoptosis by activating the PI3k/AKT/NF‐κB pathway

<p>ERα, A Key Target for Cancer Therapy: A Review</p>

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

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