miR-1204 Positioning in 8q24.21 Involved in the Tumorigenesis of Colorectal Cancer by Targeting MASPIN.

BACKGROUND: Colorectal cancer remains to be the third leading cause of cancer mortality rates. Despite the diverse effects of the miRNA cluster located in PVT1 of 8q24.21 across various tumors, the specific biological function in colorectal cancer has not been clarified. METHODS: The amplification of the miR-1204 cluster was analyzed with the cBioPortal database, while the expression and survival analysis of the miRNAs in the cluster were obtained from several GEO databases of colorectal cancer. To investigate the functional role of miR-1204 in colorectal cancer, overexpression and silencing experiments were performed by miR-1204 mimic and inhibitor transfection in colorectal cancer cell lines, respectively. Then, the effects of miR-1204 on cell proliferation were assessed through CCK-8, colony formation, and Edu assay. In addition, cell migration was evaluated using wound healing and Transwell assay. Moreover, candidate genes identified through RNA sequencing and predicted databases were identified and validated using PCR and western blot. A Dual-luciferase reporter experiment was conducted to identify MASPIN as the target gene of miR-1204. RESULT: In colorectal cancer, the miR-1204 cluster exhibited high amplification, and the expression levels of several cluster miRNAs were also significantly increased. Furthermore, miR-1204 was found to be significantly associated with disease-specific survival according to the analysis of GSE17536. Functional experiments demonstrated that transfection of miR-1204 mimic or inhibitor could enhance or decrease cancer cell proliferation and migration. MASPIN was identified as a target of miR-1204. Additionally, the overexpression of MASPIN partially rescued the effect of miR-1204 mimics on tumorigenic abilities in LOVO cells. CONCLUSION: miR-1204 positioning in 8q24.21 promotes the proliferation and migration of colorectal cancer cells by targeting MASPIN.

Kinetics and Mechanism of the Singlet Oxygen Atom Reaction with Dimethyl Ether.

We combine in situ laser spectroscopy, quantum chemistry, and kinetic calculations to study the reaction of a singlet oxygen atom with dimethyl ether. Infrared laser absorption spectroscopy and Faraday rotation spectroscopy are used for the detection and quantification of the reaction products OH, H2O, HO2, and CH2O on submillisecond time scales. Fitting temporal profiles of products with simulations using an in-house reaction mechanism allows product branching to be quantified at 30, 60, and 150 Torr. The experimentally determined product branching agrees well with master equation calculations based on electronic structure data and transition state theory. The calculations demonstrate that the dimethyl peroxide (CH3OOCH3) generated via O-insertion into the C-O bond undergoes subsequent dissociation to CH3O + CH3O through energetically favored reactions without an intrinsic barrier. This O-insertion mechanism can be important for understanding the fate of biofuels leaking into the atmosphere and for plasma-based biofuel processing technologies.

LncRNA HOTAIR promotes the migration and invasion of cervical cancer through DNMT3B/LATS1/ YAP1 pS127 axis.

Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. As a critical regulator of the Hippo pathway, the phosphorylation status of Yes-associated protein 1 (YAP1), mainly at S127, is critical for its oncogenic function. Herein, we aim to investigate the precise molecular mechanism between long noncoding RNA HOX transcript antisense RNA (HOTAIR) and YAP1 phosphorylation in regulating tumor migration and invasion. In this study, we showed that inhibition of HOTAIR significantly decreased the migration and invasion of cancer cells both in vitro and in vivo through elevating the phosphorylation level of YAP1 on serine 127, demonstrating a tumor suppressive role of YAP1 S127 phosphorylation. Through bisulfite sequencing PCR (BSP), we found that inhibition of HOTAIR dramatically increased Large Tumor Suppressor Kinase 1 (LATS1) expression by regulating LATS1 methylation via DNA methyltransferase 3ß (DNMT3B). In accordance with this observation, DNMT3B just only altered the distribution of YAP1 in the cytoplasm and the nucleus by inhibiting its phosphorylation, but did not change its total expression. Mechanistically, we discovered that HOTAIR suppressed YAP1 S127 phosphorylation by regulating the methylation of LATS1 via DNMT3B, the consequence of which is the translocation of YAP1 into the nucleus, reinforcing its coactivating transcriptional function, which in turn promotes the migration and invasion of cancer cells. Collectively, our data reveal that the phosphorylation of YAP1 S127 plays a vital role in the function of HOTAIR in tumorigenicity, and should be taken into consideration in future therapeutic strategies for cervical cancer.

FSP1-mediated ferroptosis in cancer: from mechanisms to therapeutic applications.

Ferroptosis is a new discovered regulated cell death triggered by the ferrous ion (Fe2+)-dependent accumulation of lipid peroxides associated with cancer and many other diseases. The mechanism of ferroptosis includes oxidation systems (such as enzymatic oxidation and free radical oxidation) and antioxidant systems (such as GSH/GPX4, CoQ10/FSP1, BH4/GCH1 and VKORC1L1/VK). Among them, ferroptosis suppressor protein 1 (FSP1), as a crucial regulatory factor in the antioxidant system, has shown a crucial role in ferroptosis. FSP1 has been well validated to ferroptosis in three ways, and a variety of intracellular factors and drug molecules can alleviate ferroptosis via FSP1, which has been demonstrated to alter the sensitivity and effectiveness of cancer therapies, including chemotherapy, radiotherapy, targeted therapy and immunotherapy. This review aims to provide important frameworks that, bring the regulation of FSP1 mediated ferroptosis into cancer therapies on the basis of existing studies.

Synergistic Effect of Treatment with Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Lipopolysaccharide on the Inflammatory Response of Porcine Pulmonary Microvascular Endothelial Cells.

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) often causes secondary bacterial infection in piglets, resulting in inflammatory lung injury and leading to high mortality rates and significant economic losses in the pig industry. Microvascular endothelial cells (MVECs) play a crucial role in the inflammatory response. Previous studies have shown that HP-PRRSV can infect porcine pulmonary MVECs and damage the endothelial glycocalyx. To further understand the role of pulmonary MVECs in the pathogenesis of HP-PRRSV and its secondary bacterial infection, in this study, cultured porcine pulmonary MVECs were stimulated with a HP-PRRSV HN strain and lipopolysaccharide (LPS). The changes in gene expression profiles were analyzed through transcriptome sequencing, and the differentially expressed genes were verified using qRT-PCR, Western blot, and ELISA. Furthermore, the effects on endothelial barrier function and regulation of neutrophil trans-endothelial migration were detected using the Transwell model. HP-PRRSV primarily induced differential expression of numerous genes associated with immune response, including IFIT2, IFIT3, VCAM1, ITGB4, and CCL5, whereas LPS triggered an inflammatory response involving IL6, IL16, CXCL8, CXCL14, and ITGA7. Compared to the individual effect of LPS, when given after HN-induced stimulation, it caused a greater number of changes in inflammatory molecules, such as VCAM1, IL1A, IL6, IL16, IL17D, CCL5, ITGAV, IGTB8, and TNFAIP3A, a more significant reduction in transendothelial electrical resistance, and higher increase in neutrophil transendothelial migration. In summary, these results suggest a synergistic effect of HP-PRRSV and LPS on the inflammatory response of porcine pulmonary MVECs. This study provides insights into the mechanism of severe lung injury caused by secondary bacterial infection following HP-PRRSV infection from the perspective of MVECs, emphasizing the vital role of pulmonary MVECs in HP-PRRSV infection.

Docosahexaenoic acid promotes M2 microglia phenotype via activating PPARγ-mediated ERK/AKT pathway against cerebral ischemia-reperfusion injury.

In ischemia-reperfusion stroke, microglia play a dual role in brain injury as well as brain repair, and promoting their switch from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype is considered to be a potential therapeutic strategy. Docosahexaenoic acid (DHA) is an essential long-chain omega-3 polyunsaturated fatty acid that exhibits potent anti-inflammatory properties in the acute phase of ischemic stroke, but its effect on microglia polarization is unknown. Thus, the objective of this study was to investigate the neuroprotective effects of DHA on rat brain following ischemia-reperfusion injury, and to investigate the mechanism by which DHA regulates microglia polarization. We administered DHA 5 mg/kg intraperitoneally daily for 3 d following a transient middle cerebral artery occlusion reperfusion model in rats. The protective effects of DHA on cerebral ischemia-reperfusion injury were detected by TTC staining, HE staining, Nissler staining, and TUNEL staining. Quantitative real-time PCR, immunofluorescence, western blot, and enzyme-linked immunosorbent assay were used to detect the expression of M1 and M2 microglia-associated markers and PPARγ-mediated ERK/AKT signaling pathway proteins. We found that DHA significantly improved brain injury by decreasing the expression of the M1 phenotypic marker (iNOS, CD16) and increasing the expression of the M2 phenotypic marker (Arg-1, CD206). DHA also increased the expression of peroxisome proliferator-activated receptor gamma (PPARγ) mRNA and protein, increased the expression of the pathway protein AKT, and decreased the expression of ERK1/2. In addition, DHA promoted the expression of anti-inflammatory factor IL-10 and decreased the expression of pro-inflammatory factors TNF-α and IL-1ß. However, the PPARγ antagonist GW9662 greatly blocked these beneficial effects. These results suggest that DHA may activate PPARγ to inhibit ERK and activate AKT signaling pathways to regulate microglia polarization, thereby reducing neuroinflammation and promoting neurological recovery to alleviate cerebral ischemia-reperfusion injury.

IGF2BP1-mediated N6-methyladenosine modification promotes intrahepatic cholangiocarcinoma progression.

N6-methyladenosine (m6A) RNA methylation and its associated RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) are involved in tumor initiation and progression. Here, we explored the biological function and clinical significance of IGF2BP1 in intrahepatic cholangiocarcinoma (iCCA). We found that IGF2BP1 expression was upregulated by H3K27 acetylation enrichment of its promoter, which positively correlated with poor clinicopathological characteristics and survival. Gain- and loss-of-function experiments showed that IGF2BP1 overexpression (knockdown) enhanced (attenuated) iCCA growth and metastasis in vitro and in vivo. Mechanistically, IGF2BP1 not only regulated the c-Myc/p16 axis to promote iCCA growth and inhibit senescence, but also activated the ZIC2/PAK4/AKT/MMP2 axis to induce tumor metastasis. More importantly, BTYNB, a recently identified IGF2BP1 inhibitor, exerted promising anti-tumor efficacy in a patient-derived xenograft (PDX) model, and IGF2BP1 conditional knockout (cKO) reduced the tumor burden. These results demonstrate the crucial role of IGF2BP1 in iCCA progression via m6A-dependent modification, highlighting IGF2BP1 as a potential therapeutic target in iCCA.

Regulators of epigenetic change in ferroptosis­associated cancer (Review).

The occurrence of tumors is associated with the upregulation or downregulation of certain genes. The identification of novel tumor therapies has revealed that regulation of tumor cell death can either promote or suppress the occurrence and development of tumors. Iron­dependent lipid free oxygen radical accumulation causes tumor cells to die by ferroptosis, a form of regulated cell death. Multiple mechanisms mediate this mode of cell death, including redox homeostasis, iron metabolism, mitochondrial activity, breakdown of amino acids, lipids and sugars and epigenetic regulatory and disease­associated signaling pathways. The present review discussed epigenetic mechanism of ferroptosis with the aim of providing novel insight for optimization of the effects of antitumor therapy.

COUP-TFII promotes metastasis and epithelial-to-mesenchymal transition through upregulating Snail in human intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. The overexpression of COUP-TFII has been observed in several types of malignancies. However, its role in ICC progression remains unclear. In this study, we found that the protein level of COUP-TFII was increased, but the mRNA level was unchanged in ICC tissues. High protein expression was positively associated with tumor size, lymph node metastasis, and poor prognosis in ICC patients. Furthermore, the overexpression of COUP-TFII promoted the proliferation, migration, and invasion of ICC cells in vitro and enhanced tumor growth and metastasis in nude mouse models. Mechanistic studies revealed that COUP-TFII induced epithelial-to-mesenchymal transition in ICC cells by upregulating Snail expression. Moreover, the activation of PI3K/AKT signaling led to the upregulation of COUP-TFII protein expression in ICC. Together, these findings indicate that COUP-TFII promotes epithelial-to-mesenchymal transition and metastasis in ICC and suggest that this protein is a potential target for adjuvant therapy for these patients.

Dihydromethysticin, a natural molecule from Kava, suppresses the growth of colorectal cancer via the NLRC3/PI3K pathway.

Dihydromethysticin (DHM), a natural compound derived from Kava, has been reported to be effective against mental disorders and some malignant tumors. However, little is known about the inhibitory effect of DHM on colorectal cancer (CRC). First, we examined the impact of DHM on human colon cancer cell lines, which demonstrated that DHM inhibits proliferation, migration, and invasion and promotes apoptosis and cell cycle arrest in colon cancer cells in vitro. Using small hairpin RNA, we inhibited nucleotide-oligomerization domain-like receptor subfamily C3 (NLRC3)/phosphoinositide 3-kinase (PI3K) pathway to elucidate the partial signaling of DHM-mediated tumor suppression. Additionally, using an ectopic human CRC model, we verified whether DHM inhibits tumor growth and angiogenesis via the NLRC3/PI3K pathway in vivo. Overall, DHM showed an inhibitory effect on CRC by altering cell proliferation, migration, invasion, apoptosis, cell cycle, and angiogenesis, possibly via the NLRC3/PI3K pathway. Thus, DHM may be a promising candidate for CRC therapy.

PTPN9 induces cell apoptosis by mitigating the activation of Stat3 and acts as a tumor suppressor in colorectal cancer.

BACKGROUND: Accumulating evidence has shown that protein tyrosine phosphatases (PTPs) are involved in regulating the transduction of many signaling pathways and play important roles in modulating the progression of some cancers, but the functions of PTPs in cancers have not been well elucidated until now. Here, we aimed to identify the roles of protein tyrosine phosphatase nonreceptor type 9 (PTPN9), a cytoplasmic PTP, in the development of colorectal cancer and elucidate the regulatory mechanism involved. MATERIALS AND METHODS: Cell viability assessment, colony formation assay, caspase-3 and caspase-9 activity assay, real-time PCR, and Western blot analysis were applied. RESULTS: Our results showed that PTPN9 expression was frequently downregulated in colorectal cancer tissues compared with adjacent normal tissues. Overexpression of PTPN9 mitigated cell growth and colony formation and induced cell apoptosis in colorectal cancer. Conversely, PTPN9 knockdown promoted cell growth and survival. Moreover, PTPN9 negatively regulated the activation of Stat3 and depressed its nuclear translocation in colorectal cancer. The effects of PTPN9 knockdown on cell apoptosis were attenuated by inhibition of the Stat3 pathway. CONCLUSION: These results indicate that PTPN9 inhibits cell growth and survival by repressing the activation of Stat3 in colorectal cancer, which suggests an important underlying mechanism of regulating cell growth and provides a novel candidate therapeutic target for colorectal cancer.

Comparison of Six Automated Immunoassays With Isotope-Diluted Liquid Chromatography-Tandem Mass Spectrometry for Total Thyroxine Measurement.

BACKGROUND: Accurate serum total thyroxine (TT4) measurement is important for thyroid disorder diagnosis and management. We compared the performance of six automated immunoassays with that of isotope-diluted liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) as the reference method. We also evaluated the correlation of thyroid stimulating hormone (TSH) with TT4 measured by ID-LC-MS/MS and immunoassays. METHODS: Serum was collected from 156 patients between October 2015 and January 2016. TT4 was measured by immunoassays from Abbott (Architect), Siemens (ADVIA Centaur XP), Roche (E601), Beckman-Coulter (Dxi800), Autobio (Autolumo A2000), and Mindray (CL-1000i), and by ID-LC-MS/MS. Results were analyzed using Passing-Bablok regression and Bland-Altman plots. Minimum requirements based on biological variation were as follows: a mean bias of ≤4.5% and total imprecision (CV) of ≤3.7%. RESULTS: All immunoassays showed a correlation >0.945 with ID-LC-MS/MS; however, the slope of the Passing-Bablok regression line varied from 0.886 (Mindray) to 1.23 (Siemens) and the intercept from -12.8 (Siemens) to 4.61 (Mindray). Only Autobio, Beckman-Coulter, and Roche included the value of one in the 95% confidence interval for slope. The mean bias ranged from -10.8% (Abbott) to 9.0% (Siemens), with the lowest value noted for Roche (3.5%) and the highest for Abbott (-10.8%). Only Abbott and Roche showed within-run and total CV ≤3.7%. CONCLUSIONS: Though all immunoassays correlated strongly with ID-LC-MS/MS, most did not meet the minimum clinical requirement. Laboratories and immunoassay manufacturers must be aware of these limitations.

Relationship between the Body Mass Index and Tumor Site Postoperative Complications and Prognosis in Gastric Adenocarcinoma.

The impact of BMI on survival in gastric cancer (GC) is not clear. We sought to explore the relationship between BMI and tumor site, clinicopathologic characteristics, postoperative complications, and prognosis in GC patients. Patients who underwent gastrectomy for GC between January 2011 and June 2016 formed the study cohort (n = 827). Patients were divided into three groups according to the BMI (in kg/m²): "low" (<18.5), "normal" (18.5-24.9), and "high" (≥25.0). The preoperative level of albumin and hemoglobin in the low BMI group was lower than that in the high BMI or normal BMI group (P < 0.05). The prevalence of gastric-cardia cancer in the high BMI group was significantly higher than that in the low BMI group (P = 0.001). The prevalence of gastric-antrum cancer in the high BMI group was significantly lower than that in the low BMI group (P = 0.001) and the normal BMI group (P = 0.004). The BMI of patients with gastric-cardia cancer was significantly higher than that of patients with gastric-body cancer (P = 0.018) and gastric-antrum cancer (P < 0.001). There were no significant differences among the three groups in terms of tumor size, TNM stage, depth of tumor invasion, degree of tumor differentiation, resection margin, lymph node metastasis, or postoperative complications. BMI was not an independent factor that influenced the prognosis. We found a relationship between BMI and GC site. A low BMI may be associated with a poor prognosis and a high BMI may be related to a favorable prognosis. BMI was not an independent factor that influenced GC prognosis.

Novel markers for circulating tumor stem cells in colorectal carcinoma.

Some colorectal carcinoma (CRC) invades into vessels and has distal metastasis, largely attributable to the dissemination of tumor cells into circulation as circulating tumor cells (CTCs). Moreover, cancer stem cells (CSCs) within CTCs, which are termed as circulating tumor stem-like cells (CTSCs), are critical for formation of distal metastatic tumors. Although different cell surface markers have been used to characterize and isolate CTCs or CSCs in CRC, no good marker has been identified so far for CTSCs. Here, we show evidence that CD262+ CRC cells appeared to be highly enriched for CTSCs in CRC. CD262+ CRC cells formed more tumor spheres in culture, exhibited higher chemo-resistance, had higher ratio of developing tumors after serial adoptive transplantation in nude mice, and had higher frequency of developing distal metastatic tumor, compared to traditional CD133+ or CD44+ CRC cells. Moreover, tumor cells were significantly more frequently detected in the circulation when CD262+ CRC cells were subcutaneously transplanted. Finally, we detected high CD262 levels in the stage IV CRC specimens, which were associated with poor prognosis of the patients. Together, these data suggest CD262+ may be a novel CTSC markers and selective elimination of CD262+ CRC cells may substantially improve the current CRC therapy.

(-)-Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma.

We explored the anti-cancer capacity of (-)-oleocanthal in human hepatocellular carcinoma (HCC). (-)-Oleocanthal inhibited proliferation and cell cycle progression and induced apoptosis in HCC cells in vitro and suppressed tumor growth in an orthotopic HCC model. (-)-Oleocanthal also inhibited HCC cell migration and invasion in vitro and impeded HCC metastasis in an in vivo lung metastasis model. ( )-Oleocanthal acted by inhibiting epithelial-mesenchymal transition (EMT) through downregulation Twist, which is a direct target of STAT3. (-)-Oleocanthal also reduced STAT3 nuclear translocation and DNA binding activity, ultimately downregulating its downstream effectors, including the cell cycle protein Cyclin D1, the anti-apoptotic proteins Bcl-2 and survivin, and the invasion-related protein MMP 2. Overexpression of constitutively active STAT3 partly reversed the anti cancer effects of (-)-oleocanthal, which inhibited STAT3 activation by decreasing the activities of JAK1 and JAK2 and increasing the activity of SHP-1. These data suggest that (-)-oleocanthal may be a promising candidate for HCC treatment.

Polydatin inhibits growth of lung cancer cells by inducing apoptosis and causing cell cycle arrest.

Polydatin (PD), a small natural compound from Polygonum cuspidatum, has a number of biological functions. However, the anticancer activity of PD has been poorly investigated. In the present study, thiazolyl blue tetrazolium bromide assay was used to evaluate the inhibitory effect of PD on cell growth. Cell cycle distribution and apoptosis were investigated by flow cytometry. In addition, the expression of several proteins associated with apoptosis and cell cycle were analyzed by western blot analysis. The results demonstrated that PD significantly inhibits the proliferation of A549 and NCI-H1975 lung cancer cell lines and causes dose-dependent apoptosis. Cell cycle analysis revealed that PD induces S phase cell cycle arrest. Western blot analysis showed that the expression of Bcl-2 decreased as that of Bax increased, and the expression of cyclin D1 was also suppressed. The results suggest that PD has potential therapeutic applications in the treatment of lung cancer.

DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism.

DIM (3,3'-diindolylmethane), a small molecule compound, is a proposed cancer preventive agent that can be safely administered to humans in repeated doses. We report that administration of DIM in a multidose schedule protected rodents against lethal doses of total body irradiation up to 13 Gy, whether DIM dosing was initiated before or up to 24 h after radiation. Physiologic submicromolar concentrations of DIM protected cultured cells against radiation by a unique mechanism: DIM caused rapid activation of ataxia-telangiectasia mutated (ATM), a nuclear kinase that regulates responses to DNA damage (DDR) and oxidative stress. Subsequently, multiple ATM substrates were phosphorylated, suggesting that DIM induces an ATM-dependent DDR-like response, and DIM enhanced radiation-induced ATM signaling and NF-κB activation. DIM also caused activation of ATM in rodent tissues. Activation of ATM by DIM may be due, in part, to inhibition of protein phosphatase 2A, an upstream regulator of ATM. In contrast, DIM did not protect human breast cancer xenograft tumors against radiation under the conditions tested. In tumors, ATM was constitutively phosphorylated and was not further stimulated by radiation and/or DIM. Our findings suggest that DIM is a potent radioprotector and mitigator that functions by stimulating an ATM-driven DDR-like response and NF-κB survival signaling.

Sanguinarine is a novel VEGF inhibitor involved in the suppression of angiogenesis and cell migration.

Vascular endothelial growth factor (VEGF) is a main angiogenic factor which is known to be upregulated in lung cancer. In the present study, it was demonstrated that sanguinarine, an alkaloid obtained from the bloodroot plant, markedly repressed the VEGF-induced tube formation of human microvascular endothelial cells (HMVECs) and the migration of human A549 lung cancer cells. Furthermore, sanguinarine decreased VEGF secretion and expression in HMVECs and A549 lung cancer cells in a dose- and time-dependent manner. Additionally, sanguinarine inhibited the activation of serum starvation- and hypoxia-induced VEGF promoter activity. Sanguinarine also inhibited the VEGF-mediated Akt and p38 activation, as well as VE-cadherin protein phosphorylation. To the best of our knowledge, this is the first study demonstrating that VEGF inhibition appears to be an important mechanism involved in the antiangiogenic and anti-invasive activities of sanguinarine in lung cancer treatment.

Sanguinarine inhibits growth of human cervical cancer cells through the induction of apoptosis.

Sanguinarine, a natural benzophenanthridine alkaloid, has been shown to possess anticancer activity in vitro and in vivo. In the present study, we demonstrated that sanguinarine caused a dose-dependent inhibition of growth in HeLa and SiHa human cervical cancer cells, i.e., 2.43 µmol/l (IC50) in HeLa cells and 3.07 µmol/l in SiHa cells. Cell cycle analysis revealed that sanguinarine significantly increased the sub-G1 population, from 1.7 to 59.7% in HeLa cells and from 1.7 to 41.7% in SiHa cells. Sanguinarine caused a dose-dependent decrease in Bcl-2 and NF-κB protein expression and a significant increase in Bax protein expression. Our findings indicate that sanguinarine as an effective anticancer drug candidate inhibits the growth of cervical cancer cells through the induction of apoptosis.

[EGFR-dependent impact of indol-3-carbinol on radiosensitivity of lung cancer cells].

BACKGROUND: Indole-3-carbinol (I3C) is a naturally occurring phytochemical found in cruciferous vegetables. The aim of the present study is to investigate the influence of I3C on radiosensitivity in epidermal growth factor receptor (EGFR)-positive and EGFR-negative lung cancer cell lines. METHODS: Human lung adenocarcinoma NIH-H1975 cells and human lung squamous carcinoma NIH-H226 and NIH-H520 cells were routinely cultured in RPMI-1640. MTT assay and clonogenic assay were used to detect cell growth and survival, respectively. Western blot and RT-PRC assay was employed to detect EGFR protein and mRNA expression. RESULTS: 5 µmol/L of I3C significantly reduced radiosensitivity of EGFR-positive NIH-H1975 and NIH-H226 cells, but failed to affect radiosensitivity of EGFR-negative NIH-H520 cells. Furthermore, I3C caused an increased expression of total EGFR and pEGFR (Y845) protein in NIH-H1975 and NIH-H226 cell lines, but not in NIH-H520 cell line. A reduction of EGFR expression by EGFR-siRNA significantly inhibited I3C-caused radioresistance in NIH-H1975 cells. CONCLUSIONS: Our data presented here for the first time demonstrate that I3C reduces radiosensitivity of lung cancer cells by mediating EGFR expression, indicating that EGFR may be an important target for I3C-mediated radioresistance in lung cancer.