Construction of cellulose-based highly sensitive extended-gate field effect chiral sensor.

Chiral recognition is an emerging field of modern chemical analysis, and the development of health-related fields depends on the production of enantiomers. Cellulose is a kind of natural polymer material with certain chiral recognition ability. Limited by the chiral recognition ability of natural cellulose itself, more cellulose derivatives have been gradually developed for chiral recognition and separation. Based on the difference in action between cellulose derivatives and enantiomers, this work synthesized cellulose-tris(4-methylphenylcarbamate) (CMPC) chiral recognition mediators and a CMPC-functionalized extended-gate organic field effect transistor (EG-OFET) was constructed for the first time. Three chiral molecules were selected as model analytes to evaluate the enantiomeric recognition ability of the platform, including threonine (Thr), 2-chloromandelic acid (CA), and 1,2-diphenylethylenediamine (DPEA). The detection limit for 1,2-diphenylethylenediamine (DPEA) is down to 10-13 M. Through the amplification effect of the EG-OFET platform, the difference in the interaction between CMPC and three chiral molecules with different structures is converted into a current signal output. At the same time, the enantiomer discrimination mechanism of CMPC was further studied by means of spectroscopy and nuclear magnetic resonance.

miR-100-3p inhibits cell proliferation and induces apoptosis in human gastric cancer through targeting to BMPR2.

BACKGROUND: miR-100 has been reported to closely associate with gastric cancer (GC) initiation and progression. However, the underlying mechanism of miR-100-3p in GC is still largely unclear. In this study, we intend to study how miR-100-3p regulates GC malignancy. METHODS: The expression levels of miR-100-3p in vitro (GES-1 and GC cell lines) and in vivo (cancerous and normal gastric tissues) were examined by quantitative real-time PCR (qRT-PCR). MTT and PE/Annexin V analyses were responsible for measurement of the effects of miR-100-3p on GC cell proliferation and apoptosis. Transwell assay with or without matrigel was used to examine the capacity of migration and invasion in GC cells. The interaction of miR-100-3p with bone morphogenetic protein receptor 2 (BMPR2) was confirmed through transcriptomics analysis and luciferase reporter assay. qRT-PCR and Western blot analyses were applied to determine the expression of ERK/AKT and Bax/Bcl2/Caspase3, which were responsible for the dysfunction of miR-100-3p. RESULTS: miR-100-3p was down-regulated in GC cell lines and cancerous tissues, and was negatively correlated with BMPR2. Loss of miR-100-3p promoted tumor growth and BMPR2 expression. Consistently, the effects of miR-100-3p inhibition on GC cells were partially neutralized by knockdown of BMPR2. Over-expression of miR-100-3p simultaneously inhibited tumor growth and down-regulated BMPR2 expression. Consistently, over-expression of BMPR2 partially neutralized the effects of miR-100-3p over-expression. Further study demonstrated that BMPR2 mediated the effects downstream of miR-100-3p, which might indirectly regulate ERK/AKT and Bax/Bcl2/Caspase3 signaling pathways. CONCLUSION: miR-100-3p acted as a tumor-suppressor miRNA that down-regulated BMPR2, which consequently inhibited the ERK/AKT signaling and activated Bax/Bcl2/Caspase3 signaling. This finding provided novel insights into GC and could contribute to identify a new diagnostic and therapeutic target.

MiR-362-5p promotes the malignancy of chronic myelocytic leukaemia via down-regulation of GADD45α.

BACKGROUND: MicroRNAs (miR, miRNAs) play pivotal roles in numerous physiological and pathophysiological contexts. We investigated whether miR-362-5p act as an oncogene in chronic myeloid leukaemia (CML) and aimed to understand its potential underlying mechanisms. METHODS: We compared the miR-362-5p expression levels between CML and non-CML cell lines, and between fresh blood samples from CML patients and normal healthy controls using quantitative real-time PCR (qPCR). Cell counting kit-8 (CCK-8) and Annexin V-FITC/PI analyses were used to measure the effects of miR-362-5p on proliferation and apoptosis, and Transwell assays were used to evaluate migration and invasion. A xenograft model was used to examine in vivo tumourigenicity. The potential target of miR-362-5p was confirmed by a luciferase reporter assay, qPCR and western blotting. Involvement of the JNK1/2 and P38 pathways was investigated by western blotting. RESULTS: miR-362-5p was up-regulated in CML cell lines and fresh blood samples from CML patients, and was associated with Growth arrest and DNA damage-inducible (GADD)45α down-regulation. Inhibition of miR-362-5p simultaneously repressed tumour growth and up-regulated GADD45α expression in a xenograft model. Consistently, the knockdown of GADD45α expression partially neutralized the effects of miR-362-5p inhibition. Furthermore study suggested that GADD45α mediated downstream the effects of miR-362-5p, which might indirectly regulates the activation of the JNK1/2 and P38 signalling pathways. CONCLUSION: miR-362-5p acts as an oncomiR that down-regulates GADD45α, which consequently activates the JNK1/2 and P38 signalling. This finding provides novel insights into CML leukaemogenesis and may help identify new diagnostic and therapeutic targets.

Activation of the NF-κB pathway as a mechanism of alcohol enhanced progression and metastasis of human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC. METHODS AND RESULTS: We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in a 3-D tumor/endothelial co-culture system, we found that alcohol enhanced the migration/invasion of HepG2 cells and increased tumor angiogenesis. Consistently, higher expression of VEGF, MCP-1 and NF-κB was observed in HCC tissues of alcohol-drinkers. Alcohol induced the accumulation of intracellular reactive oxygen species (ROS) and the activation of NF-κB signaling in HepG2 cells. Conversely, blockage of alcohol-mediated ROS accumulation and NF-κB signaling inhibited alcohol-induced expression of VEGF and MCP-1, the tumor growth, angiogenesis and metastasis. CONCLUSION: This study suggested that chronic moderate alcohol consumption may promote the progression and metastasis of HCC; the oncogenic effect may be at least partially mediated by the ROS accumulation and NF-ĸB-dependent VEGF and MCP-1 up-regulation.

Effect of electroacupuncture of "Zusanli" (ST36) combined with capeOX on apoptosis and ferroptosis in nude mice with colorectal cancer. / 电针"足三里"联合capeOXæ–¹æ¡ˆå¯¹ç»“ç›´è‚ ç™Œè£¸é¼ è‚¿ç˜¤ç»†èƒžå‡‹äº¡å’Œé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. METHODS: Female Balb/c nude mice were randomly assigned to 3 groups：model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. RESULTS: Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). CONCLUSIONS: EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.

Erratum: [Corrigendum] Chloroquine potentiates the anticancer effect of sunitinib on renal cell carcinoma by inhibiting autophagy and inducing apoptosis.

[This corrects the article DOI: 10.3892/ol.2017.7635.].

Regulation of depressive-like behaviours by palmitoylation: Role of AKAP150 in the basolateral amygdala.

BACKGROUND AND PURPOSE: Protein palmitoylation is involved in learning and memory, and in emotional disorders. Yet, the underlying mechanisms in these processes remain unclear. Herein, we describe that A-kinase anchoring protein 150 (AKAP150) is essential and sufficient for depressive-like behaviours in mice via a palmitoylation-dependent mechanism. EXPERIMENTAL APPROACH: Depressive-like behaviours in mice were induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Palmitoylated proteins in the basolateral amygdala (BLA) were assessed by an acyl-biotin exchange assay. Genetic and pharmacological approaches were used to investigate the role of the DHHC2-mediated AKAP150 palmitoylation signalling pathway in depressive-like behaviours. Electrophysiological recording, western blotting and co-immunoprecipitation were performed to define the mechanistic pathway. KEY RESULTS: Chronic stress successfully induced depressive-like behaviours in mice and enhanced AKAP150 palmitoylation in the BLA, and a palmitoylation inhibitor was enough to reverse these changes. Blocking the AKAP150-PKA interaction with the peptide Ht-31 abolished the CRS-induced AKAP150 palmitoylation signalling pathway. DHHC2 expression and palmitoylation levels were both increased after chronic stress. DHHC2 knockdown prevented CRS-induced depressive-like behaviours, as well as attenuating AKAP150 signalling and synaptic transmission in the BLA in CRS-treated mice. CONCLUSION AND IMPLICATIONS: These results delineate that DHHC2 modulates chronic stress-induced depressive-like behaviours and synaptic transmission in the BLA via the AKAP150 palmitoylation signalling pathway, and this pathway may be considered as a promising novel therapeutic target for major depressive disorder.

Thermodynamically consistent master equation based on subsystem eigenstates.

Master equations under appropriate assumptions are efficient tools for the study of open quantum systems. For many-body systems, subsystems of which locally couple to thermal baths and weakly interact with each other, the local approach provides a more convenient description than the global approach. However, these local master equations are believed to generate inconsistencies with the laws of thermodynamics when intersubsystem interactions exist. Here we develop an alternative local master equation by virtue of similar approximations used in deriving the traditional Gorini-Kossakowski-Lindblad-Sudarshan master equation. In particular, we stick to using eigenstates of each subsystem to construct quantum jump operators, and the secular approximation is also employed to modify the intersubsystem interactions. Our results show that violations of thermodynamic laws will be avoided after correcting intersubsystem interactions. Finally, we study a two-qubit heat transfer model and this further shows the validity of our modified master equation.

[Correlation between Serum Interleukin-33, ß2-Microglobulin Levels and DS Stage in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the correlation between serum interleukin-33 (IL-33), ß2microglobulin (ß2-MG) levels and Durie-Salmon (DS) stage in patients with multiple myeloma (MM). METHODS: 100 MM patients admitted to the First Affiliated Hospital of Fujian Medical University from March 2019 to January 2021 were selected and divided into stage I, stage II and stage III groups according to the DS staging system. A baseline data questionnaire of patients was designed, then the relevant baseline data and laboratory test results of patients were recorded. The levels of serum IL-33 and ß2-MG of all patients were detected, and the correlation between serum IL-33, ß2-MG levels and DS stage of MM patients was analyzed. RESULTS: Among the 100 patients with MM, there were 32 cases in stage I, 39 cases in stage II and 29 cases in stage III. The levels of serum CRP and ß2-MG of patients in stage III were significantly higher than those of patients in stage I and II, and the levels of serum CRP and ß2-MG of patients in stage II were significantly higher than those of patients in stage I, the differences were statistically significant (P <0.05). The level of serum IL-33 of patients in stage III was significantly lower than that of patients in stage I and II, and the level of serum IL-33 of patients in stage II was significantly lower than that of patients in stage I, the differences were statistically significant (P <0.05). There was no statistical significant difference in other data between groups (P >0.05). Kendall's tau-b correlation analysis showed that the levels of serum CRP and ß2-MG were positively correlated with DS stage in MM patients (r =0.534, 0.776), the level of serum IL-33 was negatively correlated with DS stage in MM patients (r =-0.759). Ordered logistic regression analysis and forest plot showed that the low level of serum IL-33 and the high level of ß2-MG were the influencing factors of high DS stage in MM patients (P <0.05 ). CONCLUSION: DS stage of MM patients is closely related to the levels of serum IL-33 and ß2-MG, that is, the lower the serum IL-33 level and the higher the ß2-MG level, and the higher the DS stage of MM patients.

DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampus.

Palmitoyl acyltransferases (PATs) have been suggested to be involved in learning and memory. However, the underlying mechanisms have not yet been fully elucidated. Here, we found that the activity of DHHC2 was upregulated in the hippocampus after fear conditioning, and DHHC2 knockdown impaired fear induced memory and long-term potentiation (LTP). Additionally, the activity of DHHC2 and its synaptic expression were increased after high frequency stimulation (HFS) or glycine treatment. Importantly, fear learning selectively augmented the palmitoylation level of AKAP150, not PSD-95, and this effect was abolished by DHHC2 knockdown. Furthermore, 2-bromopalmitic acid (2-BP), a palmitoylation inhibitor, attenuated the increased palmitoylation level of AKAP150 and the interaction between AKAP150 and PSD-95 induced by HFS. Lastly, DHHC2 knockdown reduced the phosphorylation level of GluA1 at Ser845, and also induced an impairment of LTP in the hippocampus. Our results suggest that DHHC2 plays a critical role in regulating fear memory via AKAP150 signaling.

Radioprotection of 4-hydroxy-3,5-dimethoxybenzaldehyde (VND3207) in culture cells is associated with minimizing DNA damage and activating Akt.

Vanillin is a naturally occurring compound and food-flavoring agent with antioxidant and antimutagenic activities. In present study, we explored the radioprotective effect of a novel vanillin derivative VND3207 (4-hydroxy-3,5-dimethoxybenzaldehyde). VND3207 has a much higher potential in scavenging hydroxyl radical and superoxide radical than vanillin as indicated in the ESR spin-trapping measurement, and it can effectively protect plasmid DNA against 10-50 Gy gamma-ray induced breaks in vitro at the concentrations as low as 10-20 microM. Using human lymphoblastoid AHH-1 cells and human fibroblastoid HFS cells, we demonstrated that VND3207 at 5-40 microM concentrations significantly attenuated the inhibition of proliferation and occurrence of apoptosis produced by 1-8 Gy gamma-irradiation. In the cultured cells, VND3207 significantly decreased the initial production and residual level of DNA double-strand breaks (DSBs) induced by 2 or 8 Gy irradiation. Treatment of VND3207 enhanced the level of DNA-PKcs protein, a critical component of DNA DSB repair pathway in the cells with or without gamma-irradiation. Consistently, the phosphorylation of Akt protein, a mediator of survival signal, as well as its substrate GSK3beta was concurrently increased by VND3207. Our results suggest that VND3207 has radioprotection effect through its capabilities as a powerful antioxidant, in minimizing DNA damage, and activating survival signal Akt pathway, and it may be of value in the development of radioprotective compounds.

[Effect of Blocking PYR Complex Binding to DNA Site by Peptide Nucleic Acid on γ-Globin Gene Expression].

OBJECTIVE: To investigate the effect of blocking polypyrimidine complex binding to DNA site by using peptide nucleic acid (PNA) on γ-globin gene expression. METHODS: PYR-PNA, ß-PNA and RS-PNA (random sequence-PNA) were designed and synthesized, then were transfected into K562 cells with the cationic liposome lipofectamine 2000 used as vector. The expression of γ-globin gene at both the transcriptional and translational level was detected by RT-PCR and the Western blot respectively at 24 h, 48 h and 72 h after transfection with PNAs. RESULTS: Compared with RS-PNA and control groups, the expression of γ-globin gene at mRNA and protein levels in PYR-PNA group was significantly up-regulated(P<0.05), especially at 48 h after tranfection, the levels of mRNA and protein in PYR-PNA group were increased by 2.0 and 2.5 times than those in control group, respectively. CONCLUSION: PYR-PNA can significantly up-regulate the expression of γ-globin gene in K562 cells, this study may provide a new research idea for gene therapy of ß-thalassemia.

#2714, a novel active inhibitor with potent G2/M phase arrest and antitumor efficacy in preclinical models.

Arresting cell cycle has been one of the most common approaches worldwide in cancer therapy. Specifically, arresting cells in the G2/M phase is a promising therapeutic approach in the battle against lung cancer. In the present study, we demonstrated the anticancer activities and possible mechanism of compound #2714, which can prompt G2/M phase arrest followed by cell apoptosis induction in Lewis lung carcinoma LL/2 cells. In vitro, #2714 significantly inhibited LL/2 cell viability in a concentration- and time-dependent manner while exhibiting few toxicities on non-cancer cells. The mechanism study showed that cell proliferation inhibition due to the treatment with #2714 correlated with G2/M phase arrest and was followed by LL/2 cell apoptosis. The characterized changes were associated with the downregulation of phosphorylated cell division cycle 25C (Cdc25C) and upregulation of p53. Apoptosis-associated activation of cleaved caspase-3 was also detected. Moreover, #2714 strongly attenuated LL/2 cell proliferation by disrupting the phosphorylation of p44/42 mitogen-activated protein kinase (MAPK). In vivo, intraperitoneal administration of #2714 (25-100 mg/kg/day) to mice bearing established tumors in xenograft models significantly prevented LL/2 tumor growth (58.1%) without detectable toxicity. Compound #2714 significantly increased apoptosis in LL/2 lung cancer cells in mice models, as observed via terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, and the data from an immunohistochemical analysis showed that #2714 remarkably inhibited the proliferation and angiogenesis of lung cancer in vivo. Taken together, our data suggest that #2714 has a high potential anti-lung cancer efficacy with a pathway-specific mechanism of G2/M phase arrest and subsequent apoptosis induction both in vitro and in vivo; its potential to be an anticancer candidate warrants further investigation.

Chloroquine potentiates the anticancer effect of sunitinib on renal cell carcinoma by inhibiting autophagy and inducing apoptosis.

Sunitinib based adjuvant chemotherapy combined with chloroquine (CQ) for the treatment of renal cell carcinoma (RCC) is in clinical trials; however, its anti-RCC effect and the mechanism remain unclear. In the present study, the anti-RCC effect of sunitinib with CQ and the underlying mechanism was investigated. An MTT assay demonstrated that CQ enhanced the proliferation inhibitory effect of sunitinib against the OS-RC-2 RCC cell line. CQ inhibited sunitinib-induced autophagy in OS-RC-2, which was evidenced by the inhibition of autophagic vacuoles, acidic vesicular organelle formation, light chain 3 (LC3)-II recruitment to the autophagosomes and the conversion of LC3-I to LC3-II, as induced by sunitinib. The inhibition of autophagy by CQ enhanced sunitinib-induced apoptosis, which was characterized by the activation of caspase-3, caspase-9, Bcl-2 and p53. Additionally, the exposure of OS-RC-2 cells to CQ and sunitinib resulted in the inhibition of AKT, tuberous sclerosis complex 2, mechanistic target of rapamycin and p70 ribosomal S6 kinase, which are associated with cell proliferation. In in vivo study, a combination of sunitinib with CQ in mice significantly reduced OS-RC-2 cell xenograft growth compared with the sunitinib alone group. In conclusion, the present study demonstrated that CQ may enhance the anti-RCC effect of sunitinib by inhibiting the autophagy induced by sunitinib, and enhance the rate of apoptosis. Inhibiting cell proliferation may also serve a role in the synergistic antitumor effect of sunitinib and CQ. These data suggest that combination therapy of sunitinib with CQ may be a promising strategy for adjuvant chemotherapy in RCC.

Effect of Ligustrazine on liver injury after burn trauma.

This study was designed to investigate the effect of Ligustrazine on burn-induced liver injury as well as the activation of nuclear factor kappaB (NF-kappaB) in severely burned rats. Sprague-Dawley rats were divided into three groups: (1) sham group, rats who underwent sham burn; (2) control group, rats given third-degree burns over 30% total body surface area (TBSA) and lactated Ringer solution for resuscitation; (3) Ligustrazine group, rats given burn and lactated Ringer's solution with Ligustrazine inside for resuscitation. Liver injury was assessed at 24 h post-burn by serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as liver wet/dry weight ratio. Liver myeloperoxidase (MPO) activity was also analyzed. Hepatic NF-kappaB activity was examined by electrophoretic mobility shift assay (EMSA). Burn results in hepatic dysfunction and increased hepatic NF-kappaB activity, elevated liver wet/dry ratio and hepatic MPO activity. Ligustrazine inhibited these changes and alleviated burn-mediated hepatic dysfunction. The data indicated that Ligustrazine has a protective effect on burn-induced liver injury and possible mechanism may be attributed to its inhibitory action on the activation of NF-kappaB following burn trauma.

EDAG-1 promotes proliferation and invasion of human thyroid cancer cells by activating MAPK/Erk and AKT signal pathways.

Erythroid differentiation-associated gene (EDAG) is differentially expressed in normal hematopoietic progenitor/stem cells and a variety of embryonic tissues. High EDAG-1 expression is also found in human thyroid cancer cells and peripheral blood of patients with leukemia, but its functional significance was unclear. Current study aims to further clarify the expression pattern of EDAG-1 and tests its roles in proliferation and invasion of human thyroid cancer cells in vitro and in vivo. To this end, we have performed gain-of-function and loss-of-function studies to clarify how EDAG-1 regulates the proliferation, invasion, and adhesion ability of human thyroid cancer cells SW579cells. We found that overexpression of EDAG-1 promoted the proliferation, invasion, and adhesion of human thyroid cancer cells, whereas silencing of EDAG-1 reversed all these changes and reduced the tumorigenesis risk of nude mice. Mechanistically, we found that overexpression of EDAG-1 activated the MAPK/Erk and AKT signal pathways. These findings provide novel insights of the role of EDAG-1 in thyroid tumors, and may have direct clinical implication.

YL4073 is a potent autophagy-stimulating antitumor agent in an in vivo model of Lewis lung carcinoma.

Cancer cells activate autophagy in response to anticancer therapies. Autophagy induction is a promising therapeutic approach to treat cancer. In a previous study, YL4073 inhibited the growth of liver cancer and induced liver cancer cell apoptosis. Here, we demonstrated the anticancer activity and specific mechanisms of YL4073 in Lewis lung carcinoma LL/2 cells. Our results show that YL4073-induced autophagy was followed by apoptotic cell death. The anticancer and autophagy stimulating efficacy was confirmed by several factors, including the appearance of autophagic vacuoles, formation of acidic vesicular organelles, recruitment of microtubule-associated protein 1 light chain 3 II (LC3-II) to the autophagosomes, conversion and cleavage of LC3-I to LC3-II, upregulation of Beclin 1 expression, and formation of the Atg12-Atg5 conjugate in LL/2 cells after YL4073 treatment for 24 or 48 h. Furthermore, P53 activation and p-histone H3 phosphorylation occurred after cell exposure to YL4073 for 48 h, suggesting that cell apoptosis had occurred. Pharmacological inhibition of autophagy using 3-methyladenine increased cell apoptosis. Molecular level studies revealed that YL4073 inhibited survival signalling by blocking the activation of Akt and mTOR phosphorylation and reduced the expression of p-mTOR downstream targets for phosphorylation, including p70S6K, p-TSC, p-MAPK, and p-AMPK. This suggests that the Akt/mTOR/p70S6K and TSC/MAPK/AMPK pathways are involved in the effects of YL4073 treatment in LL/2 cells. In addition, YL4073 significantly inhibited LL/2 tumor growth and induced apoptosis in vivo. These data suggest that YL4073 has a significant anticancer effect, with a pathway-specific mechanism of autophagy both in vitro and in vivo.