Human Large Cell Lung Carcinoma Research Articles

LCMR1 Promotes Large-Cell Lung Cancer Proliferation and Metastasis by Downregulating HLA-Encoding Genes.

Lung cancer is notorious for its high global morbidity and mortality. Here, we examined whether the LCMR1 gene, which we previously cloned from a human large-cell lung carcinoma cell line, contributes to the proliferation and metastasis of large-cell lung carcinoma. To this end, we performed pan-cancer and non-small cell lung cancer (NSCLC) cell line-based LCMR1 expression profiling. Results revealed that LCMR1 was expressed at high levels in most solid tumors, including NSCLC. LCMR1 expression was the highest in the 95D large cell lung cancer cell line. Functional studies using lentivirus-based knockdown revealed that LCMR1 was critical for the proliferation, migration, and invasion of cultured large cell lung cancer cells. Moreover, blocking this gene significantly reduced tumor growth in a 95D cell xenograft mouse model. A multiple sequence-based assay revealed a mechanism by which LCMR1 diminished the RNA Pol II occupancy at the promoter of human leukocyte antigen (HLA)-encoding genes to prevent their transcription. The HLA genes play vital roles in cancer-specific antigen presentation and anticancer immunity. A correlation assay using TCGA database identified a negative relationship between the expression levels of LCMR1 and HLA coding genes. Taken together, our findings demonstrate that LCMR1 is required for large cell lung cancer cell growth and invasion and suggest its potential as a valid target in clinical treatment.

Comprehensive Characterization of Human Lung Large Cell Carcinoma Identifies Transcriptomic Signatures with Potential Implications in Response to Immunotherapy.

Lung cancer is the leading cause of cancer mortality worldwide, with non-small cell lung cancer (NSCLC) being the most prevalent histology. While immunotherapy with checkpoint inhibitors has shown outstanding results in NSCLC, the precise identification of responders remains a major challenge. Most studies attempting to overcome this handicap have focused on adenocarcinomas or squamous cell carcinomas. Among NSCLC subtypes, the molecular and immune characteristics of lung large cell carcinoma (LCC), which represents 10% of NSCLC cases, are not well defined. We hypothesized that specific molecular aberrations may impact the immune microenvironment in LCC and, consequently, the response to immunotherapy. To that end, it is particularly relevant to thoroughly describe the molecular genotype–immunophenotype association in LCC–to identify robust predictive biomarkers and improve potential benefits from immunotherapy. We established a cohort of 18 early-stage, clinically annotated, LCC cases. Their molecular and immune features were comprehensively characterized by genomic and immune-targeted sequencing panels along with immunohistochemistry of immune cell populations. Unbiased clustering defined two novel subgroups of LCC. Pro-immunogenic tumors accumulated certain molecular alterations, showed higher immune infiltration and upregulated genes involved in potentiating immune responses when compared to pro-tumorigenic samples, which favored tumoral progression. This classification identified a set of biomarkers that could potentially predict response to immunotherapy. These results could improve patient selection and expand potential benefits from immunotherapy.

Spirostane saponins with a rearranged A/B ring system isolated from the rhizomes of Ophiopogon japonicus

In this study, the popular food and medicinal herb Ophiopogon japonicus was investigated alongside a 70% ethanol extract of its rhizomes, revealing twenty-three steroidal glycosides with four undescribed steroidal saponins, named ophiopogonols A–D. Among them, ophiopogonols A–B are two unusual spirostanols with a rearranged A/B ring system (5/7/6/5/5/6 ring system) that have not previously been identified in plants. The chemical structures of all isolated steroidal glycosides were elucidated by comprehensive analysis through chemical methods, HRESIMS, and NMR spectroscopy. Further, putative biosynthetic pathways for ophiopogonols A–B were proposed. In addition, based on traditional applications of O. japonicus, cytotoxic effects of the isolates were evaluated using human large cell lung carcinoma cells (NCI–H460 cells). Sprengerinin C displayed a remarkable cytotoxic effect with IC50 values of 2.1 ± 0.8 μM by inducing apoptosis and G2/M phase cycle arrest in the NCI–H460 cell line.

Steroidal saponins with cytotoxic effects from the rhizomes of Asparagus cochinchinensis

In the ongoing research on potent antitumor agents from the rhizomes of Asparagus cochinchinensis, seven undescribed steroidal saponins asparagusoside A–G (1–7), along with twenty known ones (8–27), were isolated and elucidated via analyzing their 1D, 2D NMR, mass spectroscopic data and chemical methods. All isolated compounds were evaluated for their cytotoxic effects against human large cell lung carcinoma cells (NCI-H460) in vitro. Among them, compounds 7, 9 and 27 showed more significant antitumor activities than the positive control cisplatin (11.56 μM) with IC50 values of 1.39, 3.04, and 2.25 μM, respectively. Further research about asparagusoside G (7) showed G0/G1 arrest in NCI-H460 cell line cycle and induced cell death by apoptosis in a dose‑dependent way.

Ethiopian Medicinal Plants Traditionally Used for the Treatment of Cancer; Part 3: Selective Cytotoxic Activity of 22 Plants against Human Cancer Cell Lines.

Medicinal plants have been traditionally used to treat cancer in Ethiopia. However, very few studies have reported the in vitro anticancer activities of medicinal plants that are collected from different agro-ecological zones of Ethiopia. Hence, the main aim of this study was to screen the cytotoxic activities of 80% methanol extracts of 22 plants against human peripheral blood mononuclear cells (PBMCs), as well as human breast (MCF-7), lung (A427), bladder (RT-4), and cervical (SiSo) cancer cell lines. Active extracts were further screened against human large cell lung carcinoma (LCLC-103H), pancreatic cancer (DAN-G), ovarian cancer (A2780), and squamous cell carcinoma of the esophagus (KYSE-70) by using the crystal violet cell proliferation assay, while the vitality of the acute myeloid leukemia (HL-60) and histiocytic lymphoma (U-937) cell lines was monitored in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) microtiter assay. Euphorbia schimperiana, Acokanthera schimperi, Kniphofia foliosa, and Kalanchoe petitiana exhibited potent antiproliferative activity against A427, RT-4, MCF-7, and SiSo cell lines, with IC50 values ranging from 1.85 ± 0.44 to 17.8 ± 2.31 µg/mL. Furthermore, these four extracts also showed potent antiproliferative activities against LCLC-103H, DAN-G, A2780, KYSE-70, HL-60, and U-937 cell lines, with IC50 values ranging from 0.086 to 27.06 ± 10.8 µg/mL. Hence, further studies focusing on bio-assay-guided isolation and structural elucidation of active cytotoxic compounds from these plants are warranted.

Anticancer Activity of Novel Plant Extracts and Compounds from Adenosma bracteosum (Bonati) in Human Lung and Liver Cancer Cells.

Cancer is the second leading cause of death globally, and despite the advances in drug development, it is still necessary to develop new plant-derived medicines. Compared with using conventional chemical drugs to decrease the side effects induced by chemotherapy, natural herbal medicines have many advantages. The present study aimed to discover the potential cytotoxicity of ethanol extract and its derived fractions (chloroform, ethyl acetate, butanol, and aqueous) of Adenosma bracteosum Bonati. (A. bracteosum) on human large cell lung carcinoma (NCI-H460) and hepatocellular carcinoma (HepG2). Among these fractions, the chloroform showed significant activity in the inhibition of proliferation of both cancerous cells because of the presence of bioactive compounds including xanthomicrol, 5,4’-dihydroxy-6,7,8,3’-tetramethoxyflavone, and ursolic acid which were clearly revealed by nuclear magnetic resonance spectroscopy (1H-NMR, 13C-NMR, Heteronuclear Multiple Bond Coherence, and Heteronuclear Single Quantum Coherence Spectroscopy) analyses. According to the radical scavenging capacity, the 5,4’-dihydroxy-6,7,8,3’-tetramethoxyflavone compound (AB2) exhibited the highest anticancer activity on both NCI-H460 and HepG2 with IC50 values of 4.57 ± 0.32 and 5.67 ± 0.09 µg/mL respectively, followed by the ursolic acid with the lower percent inhibition at 13.05 ± 0.55 and 10.00 ± 0.16 µg/mL, respectively (p < 0.05). Remarkably, the AB2 compound induced to significant increase in the production of reactive oxygen species accompanied by attenuation of mitochondrial membrane potential, thus inducing the activation of caspase-3 activity in both human lung and liver cancer cells. These results suggest that A. bracteosum is a promising source of useful natural products and AB2 offers opportunities to develop the novel anticancer drugs.

Secretagogin, a marker for neuroendocrine cells, is more sensitive and specific in large cell neuroendocrine carcinoma compared with the markers CD56, CgA, Syn and Napsin A.

A common method to distinguish large cell neuroendocrine carcinoma (LCNEC) from non-neuroendocrine large cell carcinoma (non-NE LCC) is from using specific immunohistochemistry markers, such as CgA, Syn, CD56 and Napsin A, however, the results remain controversial using these markers. Secretagogin (SCGN) is a newly discovered biomarker of neuroendocrine cells. In the present study, the expression of SCGN in 33 cases of human lung large cell carcinoma (LCC), including 17 cases of LCNEC and 16 cases of non-neuroendocrine (NE) LCC and lung cancer cell lines (A549, H1650, H358, H292 and H661). The association between SCGN expression and the clinicopathological characteristics of patients, including sex, age, clinical stage and metastasis, was analyzed. The results revealed that the different lung cancer cell lines had different expression levels of SCGN, and the SCGN protein was localized in the nucleus and cytoplasm of A549 cells detected using immunofluorescence. A total of 54.5% (18/33) of specimens positively expressed the SCGN protein. Of the 17 patients with LCNEC, only 23.5% (4/17) of cases were CgA positive, 35.29% (6/17) were Syn positive, 41.2% (7/17) were CD56 positive, and 41.2% (7/17) were Napsin A positive. However, SCGN was positively detected in 94.1% (16/17) of patients with LCNEC, which was more frequent compared with that in CgA, Syn, CD56 and Napsin A. Analysis of the clinical characteristics indicated that SCGN expression was only significantly associated with pathological type in patients with lung cancer (P<0.001). Furthermore, a positive correlation was observed between SCGN expression and CgA, Syn, and CD56 expression in patients with LCNEC. SCGN was co-localized with the NE markers (CgA, Syn, and CD56) in A549 lung cancer cells and in LCNEC tissues. Thus, SCGN displayed more sensitivity and specificity in lung cancer cells with NE differentiation. A combined analysis of SCGN and other common NE markers may be a potential tool for diagnosing these tumors.

Doxycycline inhibits electric field-induced migration of non-small cell lung cancer (NSCLC) cells

Adenocarcinoma, large cell carcinoma and squamous cell carcinoma are the most commonly diagnosed subtypes of non-small cell lung cancers (NSCLC). Numerous lung cancer cell types have exhibited electrotaxis under direct current electric fields (dcEF). Physiological electric fields (EF) play key roles in cancer cell migration. In this study, we investigated electrotaxis of NSCLC cells, including human large cell lung carcinoma NCI-H460 and human lung squamous cell carcinoma NCI-H520 cells. Non-cancerous MRC-5 lung fibroblasts were included as a control. After dcEF stimulation, NCI-H460 and NCI-H520 cells, which both exhibit epithelial-like morphology, migrated towards the cathode, while MRC-5 cells, which have fibroblast-like morphology, migrated towards the anode. The effect of doxycycline, a common antibiotic, on electrotaxis of MRC-5, NCI-H460 and NCI-H520 cells was examined. Doxycycline enhanced the tested cells’ motility but inhibited electrotaxis in the NSCLC cells without inhibiting non-cancerous MRC-5 cells. Based on our finding, further in-vivo studies could be devised to investigate the metastasis inhibition effect of doxycycline in an organism level.

Connexin43 Suppresses Lung Cancer Stem Cells.

Alterations in gap junctions and their protein components, connexins, have been associated with neoplastic transformation and drug resistance, and more recently have been shown to play important roles in cancer stem cells (CSCs). However, there is less knowledge of connexins and gap junctions in lung CSCs. To address this, Connexin43 (Cx43), the major human lung epithelial gap junction protein, was expressed ectopically in poorly expressing National Cancer Institute-125 (NCI-H125) metastatic human lung adenocarcinoma cells, and phenotypic characteristics of malignant cells and abundance of CSCs were evaluated. The ectopic expression of Cx43 resulted in the formation of functional gap junctions; a more epithelial morphology; reduced proliferation, invasion, colony formation, tumorsphere formation, pluripotency marker expression, and percentage of aldehyde dehydrogenase (ALDH)-positive cells; and increased cisplatin sensitivity. Similarly, in NCI-H522 (human lung adenocarcinoma) and NCI-H661 (human lung large cell carcinoma) cell lines, which express Cx43 and functional gap junctions endogenously, the Cx43 content was lower in tumorspheres and ALDH-positive cells than in bulk cells. These results demonstrate that Cx43 can reverse several neoplastic characteristics and reduce the abundance of human lung CSCs.

Stereochemical Structure Activity Relationship Studies (S-SAR) of Tetrahydrolipstatin.

Tetrahydrolipstatin (THL), its enantiomer, and an additional six diastereomers were evaluated as inhibitors of the hydrolysis of p-nitrophenyl butyrate by porcine pancreatic lipase. IC50s were found for all eight stereoisomers ranging from a low of 4.0 nM for THL to a high of 930 nM for the diastereomer with the inverted stereocenters at the 2,3,2'-positions. While the enantiomer of THL was also significantly less active (77 nM) the remaining five stereoisomers retained significant inhibitory activities (IC50s = 8.0 to 20 nM). All eight compounds were also evaluated against three human cancer cell lines (human breast cancers MCF-7 and MDA-MB-231, human large-cell lung carcinoma H460). No appreciable cytotoxicity was observed for THL and its seven diastereomers, as their IC50s in a MTT cytotoxicity assay were all greater than 3 orders of magnitude of camptothecin.

The investigation of ceranib-2 on apoptosis and drug interaction with carboplatin in human non small cell lung cancer cells in vitro.

Ceramide is found to be involved in inhibition of cell division and induction of apoptosis in certain tumour cells. Ceranib-2 is an agent that increases ceramide levels by inhibiting ceramidase in cancer cells. Therefore, we aimed to investigate the effects of ceranib-2 on cell survival, apoptosis and interaction with carboplatin in human non-small cell lung cancer cells. The cytotoxic effect of ceranib-2 (1-100µM) was determined by MTT assay in human lung adenocarcinoma (A549) and large cell lung carcinoma (H460) cells. Carboplatin (1-100µM) and lung bronchial epithelial cells (BEAS-2B) were used as positive controls. Morphological and ultrastructural changes were analysed by light microscope and TEM. Apoptotic/necrotic cell death and acid ceramidase activity were analysed by ELISA. Combination effects of ceranib-2 and carboplatin were investigated by MTT. The expression levels of CASP3, CASP9, BAX and BCL-2 were examined by qRT-PCR. The IC50 of ceranib-2 was determined as 22μM in A549cells and 8μM in H460cells for 24h. Morphological changes and induction of DNA fragmentation have revealed apoptotic effects of ceranib-2 in both cell lines. Ceranib-2 and carboplatin has shown synergism in combined treatment at 10 and 25μM doses in H460cells for 24h. Ceranib-2 inhibited acid ceramidase activity by 44% at 25µM in H460 cells. Finally, CASP3, CASP9 and BAX expressions were increased while BCL-2 expression was reduced in both cells. Our results obtained some preliminary results about the cytotoxic and apoptotic effects of ceranib-2 for the first time in NSCLC cell lines.

Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B) has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV) infection. Therefore, we designed that the JCPyV virus-like particle (VLP) packaged with an SP-B promoter–driven thymidine kinase suicide gene (pSPB-tk) for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp) or thymidine kinase gene (pSPB-tk) under the control of the human SP-B promoter were constructed. The promoter’s tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP’s gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV) were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter–driven GFP was specifically expressed in human lung adenocarcinoma (A549) and large cell carcinoma (H460) cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk–carrying JCPyV VLPs. In mice injected with pSPB-tk–carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV), a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

Four Cu(ii) complexes based on antitumor chelators: synthesis, structure, DNA binding/damage, HSA interaction and enhanced cytotoxicity.

Four novel copper(ii) complexes [Cu(II)(Bp4mT)(μ-Cl)]2 (), [Cu(II)(μ-Bp4mT)Br]2 (), [Cu(II)(HBpT)Cl] (), and [Cu(II)(HBpT)Br] () (Bp4mT = 2-benzoylpyridine-4-methylthiosemicarbazone, HBpT = 2-benzoylpyridine thiosemicarbazone), were synthesized and characterized using single-crystal X-ray diffraction, elemental analysis, infrared, and ultraviolet-visible spectroscopy. X-ray analysis revealed that complexes and based on the Bp4mT ligand presented dimeric structures in which the Cu(ii) ions were located in a five-coordinated distorted square-pyramidal geometry, whereas both and complexes were mononuclear with the Cu(ii) ions exhibiting a tetracoordinated square planar configuration. Their interactions with calf thymus DNA (CT-DNA) were investigated using viscosity measurements and fluorescence spectroscopy. Multispectroscopic evidence has shown interactions between these complexes and human serum albumin (HSA). All these complexes have exhibited efficient oxidative cleavage of supercoiled DNA in the presence of hydrogen peroxide, presumably via an oxidative mechanism. Furthermore, in vitro cytotoxicity studies of against human liver hepatocellular carcinoma cells (HepG-2), human large cell lung carcinoma cells (NCI-H460), and human cervical carcinoma cells (HeLa) indicated their promising antitumor activity with quite low IC50 values in the range of 0.08-1.98 μM, which are 83 times lower than those of cisplatin. The mechanistic studies revealed that four complexes, which induced early apoptosis, were involved in reactive oxygen species generation and DNA cleavage for their antitumor activities.

Digging Deep for New Compounds from the Compass Plant, Silphium laciniatum.

The compass plant, Silphium laciniatum, is an iconic perennial plant of the North American tallgrass prairie. The plants of the tallgrass prairie historically have been subjected to a number of biological and environmental stresses. Among the adaptations developed by S. laciniatum is a large deep taproot. An investigation of the secondary metabolites found in the root of a S. laciniatum specimen has led to the identification of 15 new terpenoids (3-8, 10-17, and 22), which were screened for cytotoxic activity in the NCI-H460 human large-cell lung carcinoma cell line.

Digging deep for new compounds from Silphium laciniatum

The compass plant, Silphium laciniatum, is an iconic perennial plant of the North American tallgrass prairie. The plants of the tallgrass prairie have historically been subjected to a number of biological and environmental stresses. Among the adaptations developed by S. laciniatum is a large deep taproot. This study of the chemical constituents of the root of S. laciniatum was undertaken in two phases. The first was an examination of the variation in constituents based on depth of the root material. The second was the isolation of compounds with activity against the NCI-H460 human large-cell lung carcinoma cell line. This investigation has led to the identification of fifteen new terpenoids and two new semisynthetic terpenoids.

Association of structural modifications with bioactivity in three new copper(II) complexes of Schiff base ligands derived from 5-chlorosalicylaldehyde and amino acids

Three novel structurally associated copper(II) complexes [CuII(SalCl-Gly)(H2O)2] (1), [CuII(SalCl-Ala)(H2O)] (2) and [CuII(SalCl-Gly)(bipy)]·0.5H2O (3) (SalCl-Gly=5-chloro-2-hydroxybenzylidene-glycine, SalCl-Ala=5-chloro-2-hydroxybenzylidene-alanine, bipy=2,2′-bipyridine) have been synthesized and characterized by X-ray crystallography, elemental analysis, IR and fluorescence spectroscopy. Single-crystal diffraction reveals that complex 1 is an infinite 1D zigzag chain in which SalCl-Gly serves as both a chelating and a bridging ligand, while complexes 2 and 3 are mononuclear. Cu(II) ions in complexes 1–3 exhibit distorted quasi-hexacoordinated octahedral, tetracoordinated square planar, and pentacoordinated square pyramid geometry, respectively. Their interactions with calf thymus DNA (CT-DNA) have been investigated by viscosity measurements and fluorescence spectroscopy. The apparent binding constant (Kapp) values for 1–3 are 1.02×105, 0.98×105 and 1.57×105M−1, respectively. All complexes displayed efficient oxidative cleavage of supercoiled DNA in the presence of H2O2. Complex 2, whose ligand can be regarded as a methyl-modification of SalCl-Gly of 1, showed a reduced DNA cleavage activity and a little-changed DNA-binding ability compared with 1. While attaching a 2,2′-bipyridine group to 1, the resulting complex 3 was conferred an enhanced intercalation into DNA. Moreover, cytotoxicity studies of three complexes against HepG-2 (human liver hepatocellular carcinoma) and NCI-H460 (human large-cell lung carcinoma) cells indicated that, thereto, complex 3 possessed the highest inhibition on viability of tested cells.

Synergistic anti-tumor effects of the combination of a benzofuroxan derivate and sorafenib on NCI-H460 human large cell lung carcinoma cells

Lung cancer is the most frequent and lethal human cancer in the world. Because is still an unsolved health issue, new compounds or therapeutic strategies are urgently needed. Furoxans are presented as potentials candidates for lung cancer treatment. Accordingly, we evaluated the efficacy of a benzofuroxan derivative, BFD-22, alone and combined with sorafenib against NCI-H460 cell line. We showed that BFD-22 has cytotoxic effects on the NCI-H460 cells. Importantly, the Combination Index (CI) evaluation revels that BFD-22 combined with sorafenib has a stronger cytotoxic effect. In addition, the combination induces apoptosis through extrinsic pathway, leading to TRAIL-R1/DR4-triggered apoptosis. Furthermore, BFD-22 combined with sorafenib increases ROS production and simultaneously reduces perlecan expression in the NCI-H460 cells. In accordance, tumor cells were arrested in the S-phase, and these anti-proliferative effects also inhibit cell migration. This is the first study reporting an advantage of BFD-22 combined with sorafenib as a new therapeutic strategy in the fight against lung cancer.

Synthesis and cytotoxic activity of MOM-ether analogs of isosteviol

Lung cancer is one of the most common malignancies worldwide. In this Letter, novel MOM-ether analogs of isosteviol were designed and synthesized to be tested for anticancer activities against H1299 lung cancer cell lines. The effects of these derivatives were studied in H1299 human large cell lung carcinoma cells that are null for p53 and compared to normal counterparts NL-20 normal lung epithelial cells. The initial screening of twelve MOM-ether analogs of isosteviol derivatives on H1299 lung cancer cells by MTT assay revealed that two derivatives (an ester and a carbamate) were the most potent in reducing cell viability. The IC50 values for these derivatives were determined to be 14 and 21μM respectively. We compared the cytotoxicity of the best derivatives in H1299 lung cancer cells and NL-20 normal lung epithelial cells. Both derivatives showed lower cytotoxic effects on NL-20 normal lung epithelial cells. Moreover, both derivatives induced apoptosis in H1299 lung cancer cells more than NL-20 normal lung epithelial cells.

Anticancer activity of SAHA, a potent histone deacetylase inhibitor, in NCI-H460 human large-cell lung carcinoma cells in vitro and in vivo

Suberoylanilide hydroxamic acid (SAHA), a potent pan-histone deacetylase (HDAC) inhibitor, has been clinically approved for the treatment of cutaneous T-cell lymphoma (CTCL). SAHA has also been shown to exert a variety of anticancer activities in many other types of tumors, however, few studies have been reported in large-cell lung carcinoma (LCC). Our study aimed to investigate the potential antitumor effects of SAHA on LCC cells. Here, we report that SAHA was able to inhibit the proliferation of the LCC cell line NCI-H460 in a dose- and time-dependent manner, induced cell apoptosis and G2/M cell cycle arrest, decreased AKT and ERK phosphorylation, inhibited the expression of pro-angiogenic factors (VEGF, HIF-1α) in vitro, and suppressed tumor progression in an NCI-H460 cell nude mouse xenograft model in vivo. These results indicate that SAHA can exert its strong antitumor effects in LCC patient.

In vitro cytotoxic activity of Derris scandens stem extracts against lung cancer cells and their anti-oxidant and anti-microbial effects

Derris scandens (Roxb.) Benth (DS), as Tao-Wan-Priang is popularly used in Thai traditional medicine as expectorant, antitussive and cancer cure [1]. Therefore, the objectives of this study were to investigate the cytotoxic activity of DS extracts against three types of lung cancer cell lines, such as human large cell lung carcinoma cell line (COR-L23), human lung adenocarcinoma cell line (A549) and human lung squamous carcinoma cell line (NCI-H226), and comparison with activity on normal lung cells, i.e. human lung myofibroblast cell line (MRC-5) by SRB assay[2]. Antioxidant activity by DPPH assay and anti-microbial activity were also tested [3,4]. The results showed that 95% and 50% ethanolic extracts exhibited cytotoxic activity against three lung cancer cell lines COR-L23, A549 and NCI-H226. The 95% ethanolic extract was the most active against COR-L23 (IC50= 25.20 ± 3.33 µg/ml). In addition, the 50% ethanolic extract was the most active against A549 and NCI-H226 (IC50= 6.98 ± 3.45, 18.50 ± 0.92 µg/ml, respectively). In contrast, the water extract showed low cytotoxic activity against the three types of lung cancer cell lines. All three extracts showed low anti-oxidant activity in the DPPH assay with EC50 values of 41.32 ± 3.73, 61.91 ± 0.81 and > 100 µg/ml, respectively, while BHT as a positive control exhibited an EC50 value of 10.66 ± 0.97 µg/ml. The 95% ethanolic extract showed higher anti-microbial activity against B. subtilis than against S. aureus (MIC = 20 and 40 µg/ml, respectively). The 50% ethanolic extract showed as the same effects.