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Molecular Biology Reports Jun 2024Non-small cell lung cancer (NSCLC) is the leading cause of cancer morbidity and mortality worldwide, and new diagnostic markers are urgently needed. We aimed to...
BACKGROUND
Non-small cell lung cancer (NSCLC) is the leading cause of cancer morbidity and mortality worldwide, and new diagnostic markers are urgently needed. We aimed to investigate the mechanism by which hsa_circ_0096157 regulates autophagy and cisplatin (DDP) resistance in NSCLC.
METHODS
A549 cells were treated with DDP (0 μg/mL or 3 μg/mL). Then, the autophagy activator rapamycin (200 nm) was applied to the A549/DDP cells. Moreover, hsa_circ_0096157 and Nrf2 were knocked down, and Nrf2 was overexpressed in A549/DDP cells. The expression of Hsa_circ_0096157, the Nrf2/ARE pathway-related factors Nrf2, HO-1, and NQO1, and the autophagy-related factors LC3, Beclin-1, and p62 was evaluated by qRT‒PCR or western blotting. Autophagosomes were detected through TEM. An MTS assay was utilized to measure cell proliferation. The associated miRNA levels were also tested by qRT‒PCR.
RESULTS
DDP (3 μg/mL) promoted hsa_circ_0096157, LC3 II/I, and Beclin-1 expression and decreased p62 expression. Knocking down hsa_circ_0096157 resulted in the downregulation of LC3 II/I and Beclin-1 expression, upregulation of p62 expression, and decreased proliferation. Rapamycin reversed the effect of interfering with hsa_circ_0096157. Keap1 expression was lower, and Nrf2, HO-1, and NQO1 expression was greater in the A549/DDP group than in the A549 group. HO-1 expression was repressed after Nrf2 interference. In addition, activation of the Nrf2/ARE pathway promoted autophagy in A549/DDP cells. Moreover, hsa_circ_0096157 activated the Nrf2/ARE pathway. The silencing of hsa_circ_0096157 reduced Nrf2 expression by releasing miR-142-5p or miR-548n. Finally, we found that hsa_circ_0096157 promoted A549/DDP cell autophagy by activating the Nrf2/ARE pathway.
CONCLUSION
Knockdown of hsa_circ_0096157 inhibits autophagy and DDP resistance in NSCLC cells by downregulating the Nrf2/ARE signaling pathway.
Topics: Humans; Cisplatin; NF-E2-Related Factor 2; Carcinoma, Non-Small-Cell Lung; Drug Resistance, Neoplasm; Autophagy; Signal Transduction; Lung Neoplasms; A549 Cells; Gene Expression Regulation, Neoplastic; MicroRNAs; Cell Proliferation; Cell Line, Tumor; Antioxidant Response Elements; Antineoplastic Agents; Heme Oxygenase-1
PubMed: 38822881
DOI: 10.1007/s11033-024-09552-z -
Cellular & Molecular Biology Letters May 2024Canine mammary tumors (CMTs) in intact female dogs provide a natural model for investigating metastatic human cancers. Our prior research identified elevated expression...
BACKGROUND
Canine mammary tumors (CMTs) in intact female dogs provide a natural model for investigating metastatic human cancers. Our prior research identified elevated expression of Anterior Gradient 2 (AGR2), a protein disulfide isomerase (PDI) primarily found in the endoplasmic reticulum (ER), in CMT tissues, highly associated with CMT progression. We further demonstrated that increased AGR2 expression actively influences the extracellular microenvironment, promoting chemotaxis in CMT cells. Unraveling the underlying mechanisms is crucial for assessing the potential of therapeutically targeting AGR2 as a strategy to inhibit a pro-metastatic microenvironment and impede tumor metastasis.
METHODS
To identify the AGR2-modulated secretome, we employed proteomics analysis of the conditioned media (CM) from two CMT cell lines ectopically expressing AGR2, compared with corresponding vector-expressing controls. AGR2-regulated release of 14-3-3ε (gene: YWHAE) and α-actinin 4 (gene: ACTN4) was validated through ectopic expression, knockdown, and knockout of the AGR2 gene in CMT cells. Extracellular vesicles derived from CMT cells were isolated using either differential ultracentrifugation or size exclusion chromatography. The roles of 14-3-3ε and α-actinin 4 in the chemotaxis driven by the AGR2-modulated CM were investigated through gene knockdown, antibody-mediated interference, and recombinant protein supplement. Furthermore, the clinical relevance of the release of 14-3-3ε and α-actinin 4 was assessed using CMT tissue-immersed saline and sera from CMT-afflicted dogs.
RESULTS
Proteomics analysis of the AGR2-modulated secretome revealed increased abundance in 14-3-3ε and α-actinin 4. Ectopic expression of AGR2 significantly increased the release of 14-3-3ε and α-actinin 4 in the CM. Conversely, knockdown or knockout of AGR2 expression remarkably reduced their release. Silencing 14-3-3ε or α-actinin 4 expression diminished the chemotaxis driven by AGR2-modulated CM. Furthermore, AGR2 controls the release of 14-3-3ε and α-actinin 4 primarily via non-vesicular routes, responding to the endoplasmic reticulum (ER) stress and autophagy activation. Knockout of AGR2 resulted in increased α-actinin 4 accumulation and impaired 14-3-3ε translocation in autophagosomes. Depletion of extracellular 14-3-3ε or α-actinin 4 reduced the chemotaxis driven by AGR2-modulated CM, whereas supplement with recombinant 14-3-3ε in the CM enhanced the CM-driven chemotaxis. Notably, elevated levels of 14-3-3ε or α-actinin 4 were observed in CMT tissue-immersed saline compared with paired non-tumor samples and in the sera of CMT dogs compared with healthy dogs.
CONCLUSION
This study elucidates AGR2's pivotal role in orchestrating unconventional secretion of 14-3-3ε and α-actinin 4 from CMT cells, thereby contributing to paracrine-mediated chemotaxis. The insight into the intricate interplay between AGR2-involved ER stress, autophagy, and unconventional secretion provides a foundation for refining strategies aimed at impeding metastasis in both canine mammary tumors and potentially human cancers.
Topics: Animals; Dogs; 14-3-3 Proteins; Female; Actinin; Mammary Neoplasms, Animal; Cell Line, Tumor; Chemotaxis; Autophagy; Endoplasmic Reticulum Stress; Mucoproteins; Oncogene Proteins
PubMed: 38822246
DOI: 10.1186/s11658-024-00601-w -
Molecular Immunology Jul 2024Chlamydia trachomatis (CT) is the leading cause of bacterial sexually transmitted diseases worldwide, which can cause diseases such as pelvic inflammatory disease, and...
Chlamydia trachomatis (CT) is the leading cause of bacterial sexually transmitted diseases worldwide, which can cause diseases such as pelvic inflammatory disease, and cervical and fallopian tube inflammation, and poses a threat to human health. Rosmarinic acid (RosA) is an active ingredient of natural products with anti-inflammatory and immunomodulatory effects. This study aimed to investigate the role of RosA in inhibiting autophagy-regulated immune cells-CD8+ T cells via the Ras/Raf/MEK/ERK signaling pathway in a CT-infected mouse model. Mice were inoculated with CT infection solution vaginally, and the mechanistic basis of RosA treatment was established using H&E staining, flow cytometry, immunofluorescence, transmission electron microscopy, and western blot. The key factors involved in RosA treatment were further validated using the MEK inhibitor cobimetinib. Experimental results showed that both RosA and the reference drug azithromycin could attenuate the pathological damage to the endometrium caused by CT infection; flow cytometry showed that peripheral blood CD8+ T cells increased after CT infection and decreased after treatment with RosA and the positive drug azithromycin (positive control); immunofluorescence showed that endometrial CD8 and LC3 increased after CT infection and decreased after RosA and positive drug treatment; the results of transmission electron microscopy showed that RosA and the positive drug azithromycin inhibited the accumulation of autophagosomes; western bolt experiments confirmed the activation of autophagy proteins LC3Ⅱ/Ⅰ, ATG5, Beclin-1, and p62 after CT infection, as well as the inhibition of Ras/Raf/MEK/ERK signaling. RosA and azithromycin inhibition of autophagy proteins activates Ras/Raf/MEK/ERK signaling. In addition, the MEK inhibitor cobimetinib attenuated RosA's protective effect on endometrium by further activating CD8+ T cells on a CT-induced basis, while transmission electron microscopy, immunofluorescence, and western blots showed that cobimetinib blocked ERK signals activation and further induced phagocytosis on a CT-induced basis. These data indicated that RosA can activate the Ras/Raf/MEK/ERK signaling pathway to inhibit autophagy, and RosA could also regulate the activation of immune cells-CD8+T cells to protect the reproductive tract of CT-infected mice.
Topics: Animals; CD8-Positive T-Lymphocytes; Autophagy; Female; Chlamydia Infections; Chlamydia trachomatis; Mice; Depsides; MAP Kinase Signaling System; Rosmarinic Acid; Cinnamates; ras Proteins; raf Kinases; Disease Models, Animal; Mice, Inbred C57BL
PubMed: 38820902
DOI: 10.1016/j.molimm.2024.05.007 -
Hearing Research Aug 2024The study focuses on the underlying regulatory mechanism of age-related hearing loss (ARHL), which results from autophagy dysregulation mediated by miR-130b-3p targeting...
The study focuses on the underlying regulatory mechanism of age-related hearing loss (ARHL), which results from autophagy dysregulation mediated by miR-130b-3p targeting PPARγ. We constructed miR-130b-3p knockout (antagomir) and PPARγ over-expression (OE-PPARγ) mice model by injecting mmu-miR-130b-3p antagomir and HBAAV2/Anc80-m-Pparg-T2A-mCHerry into the right ear' round window of each mouse, respectively. In vitro, we introduced oxidative stress within HEI-OC1 cells by HO and exogenously changed the miR-130b-3p and PPARγ levels. MiRNA level was detected by RT-qPCR, proteins by western blotting and immunohistochemistry. Morphology of autophagosomes was observed by electron microscopy. In vivo, the cochlea of aged mice showed higher miR-130b-3p expression and lower PPARγ expression, while exogenous inhibition of miR-130b-3p up-regulated PPARγ expression. Autophagy-related biomarkers expression (ATG5, Beclin-1 and LC3B II/I) decreased in aged mice, which reversely increased after the inhibition of miR-130b-3p. The elevation of PPARγ demonstrated similar effects. Contrarily, exogenous overexpression of miR-130b-3p resulted in the decrease of ATG5, Beclin-1 and LC3B II/I. We created oxidative stress within HEI-OC1 by HO, subsequently observed the formation of autophagosomes under electron microscope, so as the elevated cell apoptosis rate and weakened cell viability. MiR-130b-3p/PPARγ contributed to the premature senescence of these HO-induced HEI-OC1 cells. MiR-130b-3p regulated HEI-OC1 cell growth by targeting PPARγ, thus leading to ARHL.
Topics: Animals; PPAR gamma; Autophagy; MicroRNAs; Oxidative Stress; Mice, Knockout; Disease Models, Animal; Mice; Presbycusis; Cell Line; Aging; Mice, Inbred C57BL; Age Factors; Signal Transduction; Hearing; Cochlea; Apoptosis; Gene Expression Regulation
PubMed: 38820739
DOI: 10.1016/j.heares.2024.109029 -
Frontiers in Cellular and Infection... 2024Parasites possess remarkable abilities to evade and manipulate the immune response of their hosts. is a parasitic tapeworm that causes cystic echinococcosis in animals...
Parasites possess remarkable abilities to evade and manipulate the immune response of their hosts. is a parasitic tapeworm that causes cystic echinococcosis in animals and humans. The hydatid fluid released by the parasite is known to contain various immunomodulatory components that manipulate host´s defense mechanism. In this study, we focused on understanding the effect of hydatid fluid on dendritic cells and its impact on autophagy induction and subsequent T cell responses. Initially, we observed a marked downregulation of two C-type lectin receptors in the cell membrane, CLEC9A and CD205 and an increase in lysosomal activity, suggesting an active cellular response to hydatid fluid. Subsequently, we visualized ultrastructural changes in stimulated dendritic cells, revealing the presence of macroautophagy, characterized by the formation of autophagosomes, phagophores, and phagolysosomes in the cell cytoplasm. To further elucidate the underlying molecular mechanisms involved in hydatid fluid-induced autophagy, we analyzed the expression of autophagy-related genes in stimulated dendritic cells. Our results demonstrated a significant upregulation of and , indicating the induction of autophagy machinery in response to hydatid fluid exposure. Additionally, using confocal microscopy, we observed an accumulation of LC3 in dendritic cell autophagosomes, confirming the activation of this catabolic pathway associated with antigen presentation. Finally, to evaluate the functional consequences of hydatid fluid-induced autophagy in DCs, we evaluated cytokine transcription in the splenocytes. Remarkably, a robust polyfunctional T cell response, with inhibition of Th2 profile, is characterized by an increase in the expression of and genes. These findings suggest that hydatid fluid-induced autophagy in dendritic cells plays a crucial role in shaping the subsequent T cell responses, which is important for a better understanding of host-parasite interactions in cystic echinococcosis.
Topics: Dendritic Cells; Animals; Echinococcus granulosus; Autophagy; Echinococcosis; T-Lymphocytes; Mice; Lectins, C-Type; Cytokines; Female; Autophagosomes
PubMed: 38817444
DOI: 10.3389/fcimb.2024.1334211 -
Advances in Medical Sciences May 2024Epidural analgesia has emerged as a commonly used method for relieving labor pain. However, epidural-related maternal fever (ERMF) is characterized by a high occurrence...
PURPOSE
Epidural analgesia has emerged as a commonly used method for relieving labor pain. However, epidural-related maternal fever (ERMF) is characterized by a high occurrence rate and can have detrimental consequences for the well-being of both the mother and the fetus. This study aimed to investigate the functional role and underlying mechanism of dexmedetomidine (DEX) in ERMF.
MATERIALS AND METHODS
Ropivacaine (ROP)-induced human umbilical vein endothelial cells (HUVECs) were treated with DEX and/or transfected with ALKBH5 or FUNDC1 overexpression plasmid. qPCR and Western blot were adopted for mitophagy and pyroptosis marker protein detection. Autophagosomes were observed through electron microscopy, Caspase-1/PI double-positive cells were determined using flow cytometry. Inflammation-related factors were quantified using ELISA. The N-methyladenosine (mA) modification of FUNDC1 mRNA was examined using methylated RNA immunoprecipitation (MeRIP) and the binding between ALKBH5 and FUNDC1 mRNA was confirmed by RNA immunoprecipitation (RIP).
RESULTS
In ROP-induced HUVECs, there was a significant upregulation in ALKBH5 and FUNDC1, resulting in a notable increase in inflammation, pyroptosis, and mitophagy. The administration of DEX demonstrated the ability to alleviate ROP-induced pyroptosis and promote protective mitophagy. Interestingly, DEX treatment significantly reduced the interaction between ALKBH5 and FUNDC1 mRNA, while simultaneously increasing the mA level of FUNDC1 mRNA in ROP-treated cells. Moreover, the overexpression of FUNDC1 partially reversed the effects of ALKBH5 overexpression on mitophagy and pyroptosis in HUVECs.
CONCLUSIONS
DEX can promote mitophagy and inhibit pyroptosis through the ALKBH5/FUNDC1 axis in ERMF, indicating its potential as a therapeutic strategy for clinical ERMF treatment.
PubMed: 38815927
DOI: 10.1016/j.advms.2024.05.002 -
The Journal of Biological Chemistry May 2024Extracellular secretion is an essential mechanism for α-synuclein (α-syn) proteostasis. Although it has been reported that neuronal activity affects α-syn secretion,...
Extracellular secretion is an essential mechanism for α-synuclein (α-syn) proteostasis. Although it has been reported that neuronal activity affects α-syn secretion, the underlying mechanisms remain unclear. Here, we investigated the autophagic processes that regulate the physiological release of α-syn in mouse primary cortical neurons and SH-SY5Y cells. Stimulating neuronal activity with glutamate or depolarization with high KCl enhanced α-syn secretion. This glutamate-induced α-syn secretion was blocked by a mixture of NMDA receptor antagonist AP5 and AMPA receptor antagonist NBQX, as well as by cytosolic Ca chelator BAPTA-AM. Additionally, mTOR inhibitor rapamycin increased α-syn and p62/SQSTM1 (p62) secretion, and this effect of rapamycin was reduced in primary cortical neurons deficient in the autophagy regulator beclin 1 (derived from BECN1 mice). Glutamate-induced α-syn and p62 secretion was suppressed by the knockdown of ATG5, which is required for autophagosome formation. Glutamate increased LC3-II generation and decreased intracellular p62 levels, and the increase in LC3-II levels was blocked by BAPTA-AM. Moreover, glutamate promoted co-localization of α-syn with LC3-positive puncta, but not with LAMP1-positive structures in the neuronal somas. Glutamate-induced α-syn and p62 secretion were also reduced by the knockdown of RAB8A, which is required for autophagosome fusion with the plasma membrane. Collectively, these findings suggest that stimulating neuronal activity mediates autophagic α-syn secretion in a cytosolic Ca-dependent manner, and autophagosomes may participate in autophagic secretion by functioning as α-syn carriers.
PubMed: 38815862
DOI: 10.1016/j.jbc.2024.107419 -
Frontiers in Bioscience (Landmark... May 2024Ibrutinib could increase the risk of atrial fibrillation (AF) in chronic lymphocytic leukemia (CLL) patients. However, the precise mechanism underlying ibrutinib-induced...
BACKGROUND
Ibrutinib could increase the risk of atrial fibrillation (AF) in chronic lymphocytic leukemia (CLL) patients. However, the precise mechanism underlying ibrutinib-induced AF remains incompletely elucidated.
METHODS
We investigated the proportion of ibrutinib-treated CLL patients with new-onset AF. Optical mapping was conducted to reveal the proarrhythmic effect of ibrutinib on HL-1 cells. Fluorescence staining and western blot were used to compare connexins 43 and 40 expression in ibrutinib-treated and control groups. To identify autophagy phenotypes, we used western blot to detect autophagy-related proteins, transmission electron microscopy to picture autophagosomes, and transfected mCherry-GFP-LC3 virus to label autophagosomes and lysosomes. Hydroxychloroquine as an autophagy inhibitor was administered to rescue ibrutinib-induced Cx43 and Cx40 degradation.
RESULTS
About 2.67% of patients developed atrial arrhythmias after ibrutinib administration. HL-1 cells treated with ibrutinib exhibited diminished conduction velocity and a higher incidence of reentry-like arrhythmias compared to controls. Cx43 and Cx40 expression reduced along with autophagy markers increased in HL-1 cells treated with ibrutinib. Inhibiting autophagy upregulated Cx43 and Cx40.
CONCLUSIONS
The off-target effect of ibrutinib on the PI3K-AKT-mTOR signaling pathway caused connexin degradation and atrial arrhythmia via promoting autophagy.
CLINICAL TRIAL REGISTRATION
ChiCTR2100046062, https://clin.larvol.com/trial-detail/ChiCTR2100046062.
Topics: Humans; Adenine; TOR Serine-Threonine Kinases; Autophagy; Proto-Oncogene Proteins c-akt; Piperidines; Signal Transduction; Phosphatidylinositol 3-Kinases; Connexin 43; Female; Atrial Fibrillation; Connexins; Male; Aged; Middle Aged; Gap Junction alpha-5 Protein; Arrhythmias, Cardiac
PubMed: 38812314
DOI: 10.31083/j.fbl2905201 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... May 2024This study investigated the protective effect of ginsenoside Rg_1(GRg_1) on oxygen and glucose deprivation/reoxygenation(OGD/R)-injured rat adrenal...
This study investigated the protective effect of ginsenoside Rg_1(GRg_1) on oxygen and glucose deprivation/reoxygenation(OGD/R)-injured rat adrenal pheochromocytoma(PC12) cells and whether the underlying mechanism was related to the regulation of inositol-requiring enzyme 1(IRE1)-c-Jun N-terminal kinase(JNK)-C/EBP homologous protein(CHOP) signaling pathway. An OGD/R model was established in PC12 cells, and PC12 cells were randomly classified into control, model, OGD/R+GRg_1(0.1, 1, 10 μmol·L~(-1)), OGD/R+GRg_1+rapamycin(autophagy agonist), OGD/R+GRg_1+3-methyladenine(3-MA,autophagy inhibitor), OGD/R+GRg_1+tunicamycin(endoplasmic reticulum stress agonist), OGD/R+GRg_1+4-phenylbutyric acid(4-PBA, endoplasmic reticulum stress inhibitor), and OGD/R+GRg_1+3,5-dibromosalicylaldehyde(DBSA, IRE1 inhibitor) groups. Except the control group, the other groups were subjected to OGD/R treatment, i.e., oxygen and glucose deprivation for 6 h followed by reoxygenation for 6 h. Cell viability was detected by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide(MTT) assay. Apoptosis was detected by Hoechst 33342 staining, and the fluorescence intensity of autophagosomes by the monodansylcadaverine(MDC) assay. Western blot was employed to determine the expression of autophagy-related proteins(Beclin1, LC3-Ⅱ, and p62) and the pathway-related proteins [IRE1, p-IRE1, JNK, p-JNK, glucose-regulated protein 78(GRP78), and CHOP]. The results showed that GRg_1 dose-dependently increased the viability of PC12 cells and down-regulated the expression of Beclin1, LC3-Ⅱ, p-IRE1, p-JNK, GRP78, and CHOP, compared with the model group. Furthermore, GRg_1 decreased the apoptosis rate and MDC fluorescence intensity and up-regulated the expression of p62 protein. Compared with the OGD/R+GRg_1(10 μmol·L~(-1)) group, OGD/R+GRg_1+rapamycin and OGD/R+GRg_1+tunicamycin groups showed increased apoptosis rate and MDC fluorescence intensity, up-regulated protein levels of Beclin1, LC3-Ⅱ, p-IRE1, p-JNK, GRP78, and CHOP, decreased relative cell survival rate, and down-regulated protein level of p62. The 3-MA, 4-PBA, and DBSA groups exerted the opposite effects. Taken together, GRg_1 may ameliorate OGD/R-induced PC12 cell injury by inhibiting autophagy via the IRE1-JNK-CHOP pathway.
Topics: Animals; Rats; PC12 Cells; Transcription Factor CHOP; Glucose; Ginsenosides; Protein Serine-Threonine Kinases; Apoptosis; Signal Transduction; Autophagy; Endoribonucleases; JNK Mitogen-Activated Protein Kinases; Oxygen; Endoplasmic Reticulum Stress; Multienzyme Complexes
PubMed: 38812175
DOI: 10.19540/j.cnki.cjcmm.20231128.405 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... May 2024To explore the active substances exerting anti-tumour effect in lemon essential oil and the molecular mechanism inhibiting the proliferation of head and neck cancer...
To explore the active substances exerting anti-tumour effect in lemon essential oil and the molecular mechanism inhibiting the proliferation of head and neck cancer cells SCC15 and CAL33, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay(MTT) was utilized to identify the active component inhibiting the proliferation of head and neck cancer cells, namely citral. The IC_(50) of citral inhibiting the proliferation of head and neck cancer cells and normal cells were also determined. In addition, a 5-ethynyl-2'-deoxyuridine(EdU) staining assay was used to detect the effect of citral on the proliferation rate of head and neck cancer cells, and a colony formation assay was used to detect the effect of citral on tumor sphere formation of head and neck cancer cells in vitro. The cell cycle arrest and apoptosis induction of head and neck cancer cells by citral were evaluated by flow cytometry, and Western blot was used to detect the effect of citral on the expression levels of cell cycle-and apoptosis-related proteins in head and neck cancer cells. The findings indicated that citral could effectively inhibit the proliferation and growth of head and neck cancer cells, with anti-tumor activity, and its half inhibitory concentrations for CAL33 and SCC15 were 54.78 and 25.23 μg·mL~(-1), respectively. Furthermore, citral arrested cell cycle at G_2/M phase by down-regulating cell cycle-related proteins such as S-phase kinase associated protein 2(SKP2), C-MYC, cyclin dependent kinase 1(CDK1), and cyclin B. Moreover, citral increased the cysteinyl aspartate-specific proteinase-3(caspase-3), cysteinyl aspartate-specific proteinase-9(caspase-9), and cleaved poly ADP-ribose polymerase(PARP). It up-regulated the level of autophagy-related proteins including microtubule associated protein 1 light chain 3B(LC3B), sequestosome 1(P62/SQSTM1), autophagy effector protein Beclin1(Beclin1), and lysosome-associate membrane protein 1(LAMP1), suggesting that citral could effectively trigger cell apoptosis and cell autophagy in head and neck cancer cells. Furthermore, the dual-tagged plasmid system mCherry-GFP-LC3 was used, and it was found that citral impeded the fusion of autophagosomes and lysosomes, leading to autophagic flux blockage. Collectively, our findings reveal that the main active anti-proliferation component of lemon essential oil is citral, and this component has a significant inhibitory effect on head and neck cancer cells. Its underlying molecular mechanism is that citral induces apoptosis and autophagy by cell cycle arrest and ultimately inhibits cell proliferation.
Topics: Humans; Cell Proliferation; Acyclic Monoterpenes; Head and Neck Neoplasms; Apoptosis; Cell Line, Tumor; Oils, Volatile; Monoterpenes; Cell Cycle Checkpoints; Citrus; Plant Oils
PubMed: 38812137
DOI: 10.19540/j.cnki.cjcmm.20240115.704