<scp>CLEFMA</scp> induces intrinsic and extrinsic apoptotic pathways through <scp>ERK1</scp>/2 and p38 signalling in uterine cervical cancer cells

Lee, Chung‐Yuan; Hsiao, Yi‐Hsuan; Chen, Pei‐Ni; Wu, Heng-Hsiung; Lu, Chih-Yun; Yang, Shun‐Fa; Wang, Po-Hui

doi:10.1111/jcmm.17671

Cited by 5 publications

(4 citation statements)

References 44 publications

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“…ERK1/2 are downstream components of the phosphorylation cascade of MAPK, which is closely related to biological functions including cell proliferation, differentiation, migration and invasion (50,51). Although ERK1/2 protein often acts as a survival promoting factor in the MAPK family (52,53), an increasing number of studies have demonstrated that activation of the ERK1/2 protein can induce cell apoptosis (54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway

Zhang,

Qi,

et al. 2023

Oncol Rep

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Activin A, a member of the transforming growth factor-β (TGF-β) superfamily, has been implicated in the tumorigenesis and progression of various cancers. However, it remains unclear whether activin A induces apoptosis in human lung adenocarcinoma cells through the endoplasmic reticulum (ER) stress pathway. In the present study, BrdU, flow cytometry and western blotting were used to examine cell proliferation, apoptosis and protein expression, respectively. The present study revealed that activin A inhibited human lung adenocarcinoma A549 cell proliferation, induced apoptosis, and upregulated the protein levels of C/EBP homologous protein (CHOP), growth arrest and DNA damage-inducible protein 34 (GADD34), cleaved-caspase-3 and caspase-12. Furthermore, the administration of activin A did not alter the levels of suppressor of mothers against decapentaplegic 3 (Smad3) or phosphorylated (p)-Smad3 proteins, whereas, it significantly elevated the levels of ActRIIA and p-extracellular signal regulated kinase proteins 1 and 2 (ERK1/2) proteins in A549 cells. The apoptotic effects of activin A on A549 cells were attenuated by the ERK inhibitor FR180204, which also downregulated CHOP and caspase-12 protein levels. Additionally, activin A increased intracellular calcium flux in A549 cells, and the calcium ion chelator BAPTA acetoxymethyl ester (BAPTA-AM) inhibited activin A-induced A549 cell apoptosis, whereas the calcium agonist ionomycin significantly increased apoptosis of A549 cells induced by activin A. These findings indicated that the activation of the ER stress pathway resulting in apoptosis of A549 cells triggered by activin A is facilitated by the ActRIIA-ERK1/2 signaling and calcium signaling. The present findings suggest that the agonists of ERK and calcium signaling exhibit promising clinical therapeutic potential for the induction of apoptosis in lung adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway

Zhang,

Qi,

et al. 2023

Oncol Rep

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“…The way curcumin analogs boost the efficacy of anti-immune checkpoint inhibitors also represents a new research field under development [ 30 ]. Finally, among the 25 recently reviewed curcumin analogs [ 15 ], at least eight have been the subject of continuous investigations with respect to their pleiotropic anticancer effects, in 2023 alone [ 254 , 255 , 256 , 257 , 258 , 259 , 260 , 261 ]. As these molecules may overcome limitations of bioavailability and pharmacokinetics that were recently reviewed based on clinical data [ 17 ], the hope is that the current research might soon lead to clinical trials involving cancer patients for at least some of them.…”

Section: Discussionmentioning

confidence: 99%

Curcuminoids as Anticancer Drugs: Pleiotropic Effects, Potential for Metabolic Reprogramming and Prospects for the Future

Pouliquen

Trošelj

Anto³

2023

Pharmaceutics

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The number of published studies on curcuminoids in cancer research, including its lead molecule curcumin and synthetic analogs, has been increasing substantially during the past two decades. Insights on the diversity of inhibitory effects they have produced on a multitude of pathways involved in carcinogenesis and tumor progression have been provided. As this wealth of data was obtained in settings of various experimental and clinical data, this review first aimed at presenting a chronology of discoveries and an update on their complex in vivo effects. Secondly, there are many interesting questions linked to their pleiotropic effects. One of them, a growing research topic, relates to their ability to modulate metabolic reprogramming. This review will also cover the use of curcuminoids as chemosensitizing molecules that can be combined with several anticancer drugs to reverse the phenomenon of multidrug resistance. Finally, current investigations in these three complementary research fields raise several important questions that will be put among the prospects for the future research related to the importance of these molecules in cancer research.

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“…Similarly, in papillomavirus (HPV)-positive cervical cancer cells, curcumin suppresses proliferation and migration by directly targeting the viral oncoprotein E6 protein, subsequently activating p53 and p21 [186]. Interestingly, Lee et al [187] discovered that the curcumin derivative, CLEFMA, triggers intrinsic and extrinsic apoptotic pathways by activating ERK1/2 and p38 signaling [187]. Conversely, EF24 suppresses cellular migration and MMP-9 expression by inhibiting p38 signaling [188].…”

Section: Curcuminmentioning

confidence: 99%

Role of natural products in tumor therapy from basic research and clinical perspectives

Wang,

Liu,

et al. 2024

Acta Materia Medica

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Cancer is the leading cause of morbidity and mortality worldwide and is an important barrier to lengthening life expectancy in every country. Natural products are receiving increased attention from researchers globally and increasing numbers of natural products are approved for clinical studies involving cancer in recent years. To gain more insight into natural products that have undergone clinical trials for cancer treatment, a comprehensive search was conducted. The https://clinicaltrials.gov website was searched for relevant clinical trials and natural product information up to December 2022. The search terms included different types of cancers, such as colorectal, lung, breast, gynecologic, kidney, bladder, melanoma, pancreatic, hepatocellular, gastric and haematologic. Then, PubMed and Web of Science were searched for relevant articles up to February 2024. Hence, we listed existing clinical trials about natural products used in the treatment of cancers and discussed the preclinical and clinical studies of some promising natural products and their targets, indications, and underlying mechanisms of action. Our intent was to provide basic information to readers who are interested or majoring in natural products and obtain a deeper understanding of the progress and actions of natural product mechanisms of action.

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CLEFMA induces intrinsic and extrinsic apoptotic pathways through ERK1/2 and p38 signalling in uterine cervical cancer cells

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 5 publications

References 44 publications

Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway

Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway

Curcuminoids as Anticancer Drugs: Pleiotropic Effects, Potential for Metabolic Reprogramming and Prospects for the Future

Role of natural products in tumor therapy from basic research and clinical perspectives

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