Tyrosine hydroxylase inhibits HCC progression by downregulating TGFß/Smad signaling.

The alteration of metabolic processes has been found to have significant impacts on the development of hepatocellular carcinoma (HCC). Nevertheless, the effects of dysfunction of tyrosine metabolism on the development of HCC remains to be discovered. This research demonstrated that tyrosine hydroxylase (TH), which responsible for the initial and limiting step in the bio-generation of the neuro-transmitters dopamine and adrenaline, et al. was shown to be reduced in HCC. Increased expression of TH was found facilitates the survival of HCC patients. In addition, decreased TH indicated larger tumor size, much more numbers of tumor, higher level of AFP, and the presence of cirrhosis. TH effectively impairs the growth and metastasis of HCC cells, a process dependent on the phosphorylation of serine residues (S19/S40). TH directly binds to Smad2 and hinders the cascade activation of TGFß/Smad signaling with the treatment of TGFß1. In summary, our study uncovered the non-metabolic functions of TH in the development of HCC and proposes that TH might be a promising biomarker for diagnosis as well as an innovative target for metastatic HCC.

Nicotinamide adenine dinucleotide kinase promotes lymph node metastasis of NSCLC via activating ID1 expression through BMP pathway.

Metastasis is a significant cause of high mortality in lung cancer. Lymph node (LN) metastasis is the most common metastatic pathway in non-small cell lung cancer and the most crucial factor affecting the prognosis of NSCLC. Nevertheless, the molecular mechanism underlying metastasis is unknown. We demonstrated that higher NADK expression suggests worsened survival prognosis, and NADK expression positively correlates with the lymph node metastasis rate and TNM and AJCC stages in NSCLC patients. Moreover, patients with LN metastasis show higher NADK expression than those without LN metastasis. NADK can promote NSCLC progression by enhancing the migration, invasion, lymph node metastasis and growth of NSCLC cells. Mechanistically, NADK inhibits the ubiquitination and degradation of BMPR1A by interacting with Smurf1, further activating the BMPs signalling pathway and promoting ID1 transcription. In conclusion, NADK may be a potential diagnostic indicator and a novel therapeutic target for metastatic NSCLC.

Phosphorylation by IKKß Promotes the Degradation of HMGCL via NEDD4 in Lung Cancer.

Inflammation and metabolic reprogramming are hallmarks of cancer. How inflammation regulates cancer metabolism remains poorly understood. In this study, we found that 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL), the enzyme that catalyzes the catabolism of leucine and promotes the synthesis of ketone bodies, was downregulated in lung cancer. Downregulation of HMGCL was associated with a larger tumor size and a shorter overall survival time. In a functional study, overexpression of HMGCL increased the content of ß-hydroxybutyrate (ß-HB) and inhibited the tumorigenicity of lung cancer cells, and deletion of HMGCL promoted de novo tumorigenesis in KP (KrasG12D;P53f/f) mice. Mechanistically, tumor necrosis factor α (TNFα) treatment decreased the HMGCL protein level, and IKKß interacted with HMGCL and phosphorylated it at Ser258, which destabilized HMGCL. Moreover, NEDD4 was identified as the E3 ligase for HMGCL and promoted its degradation. In addition, mutation of Ser258 to alanine inhibited the ubiquitination of HMGCL by NEDD4 and thus inhibited the anchorage-independent growth of lung cancer cells more efficiently than did wild-type HMGCL. In summary, this study demonstrated a link between TNFα-mediated inflammation and cancer metabolism.

Ground glass opacity resection extent assessment trial (GREAT): A study protocol of multi-institutional, prospective, open-label, randomized phase III trial of minimally invasive segmentectomy versus lobectomy for ground glass opacity (GGO)-containing early-stage invasive lung adenocarcinoma.

Background: With widely use of computed tomography (CT) screening, an increasing number of early-stage lung cancers appearing as ground glass opacity (GGO) have been detected. Therefore, attempts have been made to investigate the feasibility of segmentectomy instead of lobectomy for those patients with GGO. However, the two recently released phase III trials failed to distinguish between GGO-containing lesions from pure solid nodules in the inclusion criteria, and the surgical methods did not distinguish between minimally invasive surgery and open thoracotomy. In addition, total lesion size≤ 2cm was taken as the inclusion criterion, instead of the solid part size recommended in the eighth edition of Union for International Cancer Control/International Association for the Study of Lung Cancer/American Joint Committee on Cancer (UICC/IASLC/AJCC) staging system. Hence, this present trial aims to figure out whether minimally invasive segmentectomy shows superiority in perioperative outcomes and non-inferiority in oncological prognosis over minimally invasive lobectomy among patients with GGO-containing clinical stage T1a-T1b lung invasive adenocarcinoma (IADC). Methods/design: Sample sizes are 1024 patients, who will be randomized into minimally invasive segmentectomy and lobectomy groups . Patients will be collected from 19 hospitals in China. Patients with peripheral mixed ground glass opacity (mGGO) with 0.5cm

Gender differences in empathy, emotional intelligence and problem-solving ability among nursing students: A cross-sectional study.

BACKGROUND: Empathy, emotional intelligence (EI) and problem-solving ability are three important characteristics that influence effective communication in clinical practice. Previous studies have not adequately explored the specific relationships between these three abilities and their gender differences among nursing students. OBJECTIVE: We sought to investigate the current state of emotional intelligence, empathy, and problem-solving ability in nursing students and to identify whether gender differences affect these three characteristics and how gender differences can be used to educate nurses on empathy. DESIGN: We conducted a cross-sectional survey. PARTICIPANTS: A total of 993 nursing students from two grade A tertiary hospitals in Hunan, China participated in this study. METHODS: Data were collected using the Empathy of Clinical Nurse Scale (ENCS), Emotional Intelligence Scale of Clinical Junior Nurses (EIS) and Social Problem-Solving Inventory (SPSI). Data were analyzed using an independent samples t-test, Pearson correlation and hierarchical multiple linear regression. RESULTS: There was no significant difference in the ENCS and SPSI scores between male and female nursing students, but male nursing students had lower EIS scores (P < 0.05). A significant association was found between ENCS, EIS and SPSI on most dimensions among female nursing students, but no significant association was found between ENCS and EIS for total scores among males. We found that problem-solving ability was the most important factor affecting the variation in empathy for both male and female nursing students through hierarchical multiple regression analysis. CONCLUSIONS: Gender differences are reflected not only in the level of emotional intelligence but also in the relationships between emotional intelligence, empathy, and problem-solving ability. Nursing educators should be aware of how gender differences can affect these three traits; this is particularly important for teaching based on students' aptitudes.

How to achieve self-growth as an intern nursing student in Intensive Care Unit: A qualitative study.

AIMS: To explore the clinical experiences of the intern nursing students who did their internship in the Intensive Care Unit (ICU) at least two months. The key point is to investigate how nursing students achieved self-development in ICUs. METHODS: Using qualitative study based on the grounded theory, we enrolled 15 intern nursing students from November 2021 to April 2022 in a Grade A hospital in Hunan Province, China. RESULTS: This study developed an explanatory theoretical framework of the interns' experience in ICUs, which was described as a comprehensive growth process for ICU interns. In this process, the intern nursing students often go through three stages: pressure period, adjustment period and growth period. Self-regulation and social interaction play a key role to help them get over the negative experiences they experienced in the stress period and achieve personal development. CONCLUSION: Clinical nursing educators could make appropriate interventions based on the characteristics of students at different intership stages in ICUs. The target training of intern nursing students should focus on their theoretical knowledge, emotion regulation, communication skills and personality optimization. In addition, clinical tutors should be trained regularly to prepare well for their important roles.

What Do We Talk About Now When We Talk About Segmentectomy for GGO?

Segmentectomy has been considered as a compromised procedure in patients with early-stage lung cancer who could not tolerate standard lobectomy. By computed tomography (CT) screening, lung cancers are increasingly detected in earlier stages, especially those appearing as ground glass opacity (GGO)-containing lesions on CT scan. This has led to the revival of segmentectomy as an intentional procedure with the aim of curing selected patients, as GGO-containing lesions represent a special group of diseases that are relatively indolent in nature and seldom have lymphatic involvement. Limited resections, especially anatomical segmentectomy, may, thus, be helpful in reducing perioperative risks and preserving higher pulmonary function for patients while retaining similar oncological outcomes. However, clinical trials focusing specifically on the role of segmentectomy in the treatment of GGO-containing lung cancers are still lacking, especially in the minimally invasive surgery setting. Emerging evidence suggests that for such lesions, the oncological non-inferiority of segmentectomy to standard lobectomymay not be limited to lesions with a size ≤ 2 cm. More importantly, it is still unclear whether segmentectomy could indeed minimize perioperative risks and to what extent it could help preserve higher pulmonary function in good-risk patients with less extent of lung parenchyma resection. Hence, it is critical to reevaluate the efficacies of minimally invasive segmentectomy including not only oncological outcomes but also perioperative results and pulmonary function changes compared with lobectomy in good-risk patients with GGO-containing lung cancers. All these remain to be explored in future studies and robust evidence is still needed to prove that patients would indeed benefit from the combination of segmentectomy and minimally invasive surgery.

Stigma and related influencing factors in postoperative oral cancer patients in China: a cross-sectional study.

PURPOSE: To examine the level of stigma and identify its influencing factors among postoperative oral cancer patients in China. METHODS: In total, 274 postoperative oral cancer patients were recruited from a Grade A Tertiary Hospital in China using convenience sampling methods. Patients completed the Social Impact Scale (SIS), Medical Coping Mode Questionnaire (MCMQ), Social Support Rating Scale (SSRS), and General Self-efficacy Scale (GSE). RESULTS: Stigma reported by postoperative oral cancer patients was moderate (50.17 ± 21.24). Stepped multiple linear regression showed that the related factors influencing their feelings of stigma were educational level (ß = - 0.110, P = 0.001), smoking (ß = - 0.152, P < 0.001), betel quid (ß = - 0.120, P = 0.001), tumor location (ß = - 0.390, P < 0.001), tumor stage (ß = 0.219, P < 0.001), self-efficacy (ß = - 0.253, P < 0.001), and confrontation (ß = - 0.117, P = 0.001) and avoidance (ß = 0.123, P < 0.001), which explained 74.2% of the total variation in stigma (F = 99.378, P < 0.001). CONCLUSIONS: Stigma was positively predicted by tumor stage and avoidance but negatively predicted by education level, smoking, betel quid, tumor location, confrontation, and self-efficacy. Further work should focus on developing interventions to reduce stigma by improving protective factors and decreasing risk factors.

Loss of DSTYK activates Wnt/ß-catenin signaling and glycolysis in lung adenocarcinoma.

Aberrant activation of Wnt/ß-catenin signaling and dysregulation of metabolism have been frequently observed in lung cancer. However, the molecular mechanism by which Wnt/ß-catenin signaling is regulated and the link between Wnt/ß-catenin signaling and cancer metabolism are not fully understood. In this study, we showed that the loss of dual serine/threonine tyrosine protein kinase (DSTYK) led to the activation of Wnt/ß-catenin signaling and upregulation of its target gene, lactate dehydrogenase (LDHA), and thus the elevation of lactate. DSTYK phosphorylated the N-terminal domain of ß-catenin and inhibited Wnt/ß-catenin signaling, which led to the inhibition of cell growth, colony formation and tumorigenesis in a lung adenocarcinoma mouse model. DSTYK was downregulated in lung cancer tissues, and its expression was positively correlated with the survival of patients with lung adenocarcinoma. Taken together, these results demonstrate that the loss of DSTYK activates Wnt/ß-catenin/LDHA signaling to promote the tumorigenesis of lung cancer and that DSTYK may be a therapeutic target.

Targeting histone deacetylase enhances the therapeutic effect of Erastin-induced ferroptosis in EGFR-activating mutant lung adenocarcinoma.

BACKGROUND: Intrinsic or acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is common, thus strategies for the management of EGFR-TKIs resistance are urgently required. Ferroptosis is a recently discovered form of cell death that has been implicated in tumorigenesis and resistance treatment. Accumulating evidence suggests that ferroptosis can be therapeutically exploited for the treatment of solid tumors; however, whether ferroptosis can be targeted to treat EGFR mutant lung cancer and/or overcome the resistance to EGFR-TKIs is still unknown. METHODS: The effect of ferroptosis inducers on a panel of EGFR mutant lung cancer cell lines, including those with EGFR-TKI intrinsic and acquired (generated by long-term exposure to the third-generation EGFR-TKI osimertinib), was determined using cytotoxicity assays. Further, drug candidates to enhance the effect of ferroptosis inducers were screened through implementing WGCNA (weighted gene co-expression network analysis) and CMAP (connectivity map) analysis. Flow cytometry-based apoptosis and lipid hydroperoxides measurement were used to evaluate the cell fates after treatment. RESULTS: Compared with EGFR-TKI-sensitive cells, those with intrinsic or acquired resistance to EGFR-TKI display high sensitivity to ferroptosis inducers. In addition, Vorinostat, a clinically used inhibitor targeting histone deacetylase, can robustly enhance the efficacy of ferroptosis inducers, leading to a dramatic increase of hydroperoxides in EGFR mutant lung cancer cells with intrinsic or acquired resistance to EGFR-TKI. Mechanistically, Vorinostat promotes ferroptosis via xCT downregulation. CONCLUSIONS: Ferroptosis-inducing therapy shows promise in EGFR-activating mutant lung cancer cells that display intrinsic or acquired resistance to EGFR-TKI. Histone deacetylase inhibitor (HDACi) Vorinostat can further promote ferroptosis by inhibiting xCT expression.

Impact of treatment modality on long-term survival of stage IA small-cell lung cancer patients: a cohort study of the U.S. SEER database.

BACKGROUND: The optimal treatment modality for patients with stage IA (T1N0M0) small-cell lung cancer (SCLC) is still unclear. METHODS: Patients who received surgical resection or chemo-radiotherapy (CRT) between January 2004 and December 2014 were identified from The Surveillance, Epidemiology and End Results (SEER) database. Surgical resection included lobectomy, wedge resection, segmentectomy with lymphadenectomy [examined lymph node (ELN) ≥1]. Propensity score match analysis was utilized to balance the baseline characteristics. RESULTS: A total of 686 stage IA SCLC cases were included: 337 patients underwent surgery and 349 patients were treated by CRT alone. Surgery achieved a better outcome than CRT alone, with an adjusted hazard ratio (HR) of 0.495. Patients who underwent lobectomy demonstrated a longer overall survival (OS), compared to those who received sublobectomy (crude cohort, median OS, 69 vs. 38 months; match cohort, median OS, 67 vs. 38 months). Patients with ELN >7 presented with longer OS than those with ELN ≤7 (crude cohort, median OS, 91 vs. 49 months; matched cohort, median OS, 91 vs. 54 months). The additional efficacy of chemotherapy or radiotherapy in patients receiving lobectomy was observed. The best prognosis was achieved in the lobectomy plus CRT cohort, with a 5-year survival rate of 73.5%. CONCLUSIONS: The prolonged survival associated with lobectomy and chemotherapy or radiotherapy presents a viable treatment option in the management of patients with stage IA SCLC.

ZNF251 promotes the progression of lung cancer by activating ERK signaling.

Aberrant activation of ERK signaling is a hallmark of lung cancer. Although constitutively activating mutations of EGFR and KRAS contribute to the hyperactivation of ERK1/2, other mechanisms remain elusive. In this study, the zinc finger protein ZNF251 was found to be upregulated in clinical lung cancer samples, and it promoted the growth of lung cancer cells and the growth of primary lung KPC cells from mouse models (Ad-Cre, KrasG12D , and P53f/f ). In studying the molecular mechanism, ZNF251 was found to inhibit the expression of dual-specificity phosphatase 6, a negative regulator of ERK activation, by directly binding to its promoter region. Taken together, our data indicate the tumor-promoting effects of ZNF251 in lung cancer and suggest that ZNF251 is a therapeutic target.

Psychological resilience and related influencing factors in postoperative non-small cell lung cancer patients: A cross-sectional study.

OBJECTIVE: The psychological resilience of postoperative non-small cell lung cancer (NSCLC) patients is influenced by many factors. The purpose of this study is to investigate the current state of psychological resilience and identify its influencing factors in postoperative NSCLC patients. METHODS: This descriptive cross-sectional study used a convenience sampling method and recruited 382 inpatients from two Class A hospitals in Hunan, China. The Connor-Davidson Resilience Scale (CD-RISC), Strategies Used by People to Promote Health (SUPHH), Medical Coping Modes Questionnaire (MCMQ), and Multidimensional Scale of Perceived Social Support (MSPSS) were used. RESULTS: Postoperative NSCLC patients' psychological resilience was at a low level, with a score of (57.18 ± 8.55). Stepped Linear Regression showed that the related influencing factors of psychological resilience of postoperative NSCLC patients were age (ß = -0.313, P < .001), family average income (ß = 0.143, P < .001), self-efficacy (ß = 0.416, P < .001), confrontation (ß = 0.116, P < .001) and acceptance-resignation (ß = -0.155, P < .001), which could explain 58.0% of the total variation in psychological resilience (F = 103.68, P<.001). CONCLUSIONS: Psychological resilience is positively predicted by average income, self-efficacy, confrontation, but negatively predicted by age and acceptance-resignation. Self-efficacy is the most important variable influencing psychological resilience in postoperative NSCLC patients. In the future, a series of targeted interventions need to be implemented to strengthen patients' self-efficacy and psychological resilience, which can also improve the quality of life of postoperative NSCLC patients.

Low Expression of ASK1-Interacting Protein-1 Is Significantly Correlated with Tumor Angiogenesis and Poor Survival in Patients with Early Stage Non-Small Cell Lung Cancer.

OBJECTIVE: To investigate the expression of tumor suppressor protein ASK1-interacting protein-1 (AIP1) in cancer tissues of patients with early-stage non-small cell lung cancer (NSCLC) and its correlation with tumor progression, tumor angiogenesis and prognosis. METHODS: A total of 136 patients with stage I NSCLC who underwent radical resection of lung cancer in Qianfoshan Hospital of Shandong Province from January 2011 to December 2011 were enrolled. Immunohistochemistry was used to detect AIP1 protein in tumor tissues. Vascular endothelial CD34 immunohistochemical staining was used to count intratumoral microvessel density (MVD). SPSS 19.0 software was used to analyze the relationship between AIP1 protein expression and clinicopathological features, tumor angiogenesis and prognosis. RESULTS: Low expression of AIP1 was more common in tumor tissues with high MVD, and patients with low expression of AIP1 were more likely to have tumor recurrence. Multivariate analysis showed that low expression of AIP1 had predictive value for overall survival, disease-free survival, and disease-specific survival. CONCLUSION: Downregulation of AIP1 protein expression is associated with lung cancer progression, tumor angiogenesis and poor prognosis. Consequently, AIP1 may prove to be an important predictor of recovery from lung cancer and could become a new therapeutic target for lung cancer treatment.

SREBP2 is upregulated in esophageal squamous cell carcinoma and co­operates with c­Myc to regulate HMGCR expression.

Dysregulations of the mevalonate pathway (MVA) have been previously identified. Our previous study demonstrated that 3­hydroxy­3­methylglutaryl­coenzyme A reductase (HMGCR), the rate­limiting enzyme of the MVA pathway, was upregulated in esophageal squamous cell carcinoma (ESCC) and statin­inhibited ESCC tumorigenesis. However, the underlying mechanism of HMGCR regulation in ESCC remains unknown. In the present study, western blotting and immunohistochemistry analysis demonstrated that sterol regulatory element­binding protein 2 (SREBP2), the master regulator for HMGCR, was upregulated in ESCC clinical samples. Overexpression of SREBP2 expression in ESCC cell lines promoted the growth, migration and colony formation of cancer cells in the MTT, Boyden chamber and soft agar assays, respectively, which was inhibited by lovastatin. Downregulation of SREBP2 expression in ESCC cell lines inhibited the viability, and migration and colony formation abilities of cancer cells. Assessment of the molecular mechanism demonstrated that SREBP2 interacted with c­Myc and cooperated with c­Myc to activate HMGCR expression. Collectively, the present study identified SREBP2 as an oncogene associated with the tumorigenesis of ESCC and further demonstrated the therapeutic effects of statins in ESCC.

Low expression level of ASK1-interacting protein-1 correlated with tumor angiogenesis and poor survival in patients with esophageal squamous cell cancer.

OBJECTIVE: To investigate the expression of tumor suppressor protein ASK1-interacting protein-1 (AIP1) in human esophageal squamous cell carcinoma (ESCC) and its role in tumor progression, angiogenesis, and prognosis. METHODS: A total of 117 biopsy samples were obtained from ESCC patients. None of the patients had distant metastasis before surgery, and did not receive preoperative chemotherapy or radiotherapy. Immunohistochemistry was used to detect the expression of AIP1 protein and vascular endothelial growth factor receptor 2 (VEGFR2) in ESCC specimens collected from 117 patients who underwent esophageal cancer radical surgery. Microvessel density (MVD) was evaluated by immunohistochemical staining of vascular endothelial CD34. The correlation between AIP1 protein and clinicopathological characteristics, tumor angiogenesis, and prognosis was analyzed. RESULTS: The downregulation of AIP1 protein in esophageal carcinoma tissues was detected in 63 cases. This downregulation significantly correlated with lymph node metastasis, clinicopathological staging, and tumor MVD (P<0.05). Survival analysis showed that ESCC patients with a low expression of AIP1, a high expression of VEGFR2, and a high level of MVD had a lower 5-year survival rate (P<0.05). Multivariate analysis confirmed that the downregulation of AIP1 significantly affected patient survival. CONCLUSION: The downregulation of AIP1 correlated with ESCC progression, tumor angiogenesis, and poor prognosis. AIP1 could be a promising biomarker for predicting ESCC prognosis and a potential target for anti-angiogenic therapy.

Sublobar resections for small-sized stage Ia lung adenocarcinoma: a Sino-Japanese multicenter study.

BACKGROUND: Segmentectomy for small-sized stage Ia non-small cell lung cancer (NSCLC) may be comparable to lobectomy regarding prognosis and local recurrence. However, the clinical results of wedge resection for such patients are still under debate. In this international multicenter study, we retrospectively studied surgical outcomes of sublobar resections for patients with small-sized stage Ia adenocarcinoma to elucidate whether wedge resection is inferior to segmentectomy for such patients. METHODS: Between March 2000 and August 2011, 173 patients underwent segmentectomy (group I), and 181 patients underwent wedge resection (group II) at three institutions in Japan and China. The tumor was defined as Ground glass opacity (GGO) type when the proportion of GGO was equal or more than 50% in HRCT, while solid type was defined as the proportion of GGO less than 50%. Clinicopathologic factors, local recurrence rate, and survival were compared. RESULTS: The two groups were similar in sex, comorbidity rate, and composition of Noguchi type. There was no in-hospital death. Postoperative morbidity rate of group I was significantly higher than that of group II (11.0% vs. 2.2%, P=0.016). Local recurrence rates were similar between group I (4.0%) and group II (4.4%), while no patient with GGO type tumors had local recurrence. Overall and lung cancer-specific survivals were of no significant difference between the two groups. Lung cancer-specific survival rates at 10 years were significantly better in patients with GGO type tumors than in those with solid type tumors (100% vs. 76.9%, P<0.001). In multivariate Cox regression analyses of lung cancer-specific survival of all patients, GGO type turned out to be an independent prognostic factor, while extent of resection did not have any influence. CONCLUSIONS: Our data suggests that sublobar resection is an acceptable procedure for small lung adenocarcinomas without nodal involvement, and wedge resection may not be inferior to segmentectomy for small GGO type tumors. Our study also demonstrates that GGO type is an independent prognostic factor of disease-free survival for small-sized (diameter ≤2.0 cm) stage Ia lung adenocarcinomas.

Effect of hyperoside on the apoptosis of A549 human non­small cell lung cancer cells and the underlying mechanism.

Hyperoside (HY) is a major pharmacologically active component from Prunella vulgaris L. and Hypericum perforatum. The present study aimed to determine the anticancer effect of HY and determine the underlying mechanisms involved. Human A549 cells were treated with HY (10, 50 and 100 µM), and cell viability was detected by an MTT assay. Cell apoptosis and mitochondrial membrane potential were determined by flow cytometry. Western blot analysis was used to identify the expression of apoptosis­associated proteins and phosphorylation of MAPK. The present study demonstrated that HY significantly inhibited the viability of A549 cells in a time­ and dose­dependent manner, and enhanced the percentage of apoptotic cells. HY also significantly increased the protein phosphorylation of p38 mitogen­activated protein kinase (MAPK) and c­Jun N­terminal kinase (JNK), disrupted mitochondrial membrane penetrability, and triggered the release of mitochondrial cytochrome c and apoptosis­inducing factor into the cytosol. Treatment with HY also activated the expression of caspase­9 and caspase­3. These results suggested that HY­induced apoptosis was associated with activation of the p38 MAPK­ and JNK­induced mitochondrial death pathway. HY may offer potential for clinical applications in treating human non­small cell lung cancer and improving cancer chemotherapy.