A549 Human Cancer Cells Research Articles

부추의 함황화합물이 인체 암세포 증식에 미치는 영향

To develop Allium tuberosum L. as a cancer preventive food material, thiosulfinates and biological active components were isolated from Allium tuberosum L. and the apoptotic effects of thiosulfinates in human cancer cells were examined. Thiosulfinates decreased viable cell numbers in dose- and time-dependent manners. Thiosulfinates at the 20 /mL concentration inhibited more than 60% cell proliferation in HepG2 and A549 human cancer cells, respectively. Also the morphology of cells treated with thiosulfinates of 30 /mL concentration was distorted with shrunken cell mass while the cell number was lower than that of control cells. The values in the HepG2 cells were higher than those of the A549 cells. Thiosulfinates at the 30 /mL concentration showed the formation of apoptotic bodies and a nuclear condensation, and an increase in the cell populations of the sub-G1 phase in the HepG2 cells. These results indicate that thiosulfinates from Allium tuberosum L. inhibited cell proliferation in HepG2 via apoptosis.

Mechanisms of nicotine-induced resistance to treatment with chemotherapy and radiotherapy

e22008 Background: Nicotine (NIC), used for smoking cessation in cancer patients, is associated with increased tumor growth, angiogenesis, migration, invasion, growth factor production, and inhibition of apoptosis. The effects of NIC on the efficacy of radiotherapy (XRT) and/or chemotherapy (CT) have not been well characterized. Methods: A review of the literature produced a construct demonstrating that NIC generates more than 100 interactions with 40 proteins involved in tumor promotion and progression. From this construct, nicotinic acetylcholine receptors (nAChR), PI3K/Akt, and MAPK were identified as potential critical upstream targets modulating the effects of NIC. The effect of NIC on cell proliferation, cell survival, and protein activation was analyzed following CT, XRT, or chemoradiotherapy (CRT) in FaDu, A549, and H460 human cancer cell lines. Results: Proliferation measured with the WST-1 (tetrazolium) assay demonstrated that NIC increased proliferation following cisplatin, XRT, and cisplatin with XRT. NIC administration increased cell survival (colony survival) following XRT and following CT (cisplatin, doxorubicin, or etoposide) regimens in all cell lines. nAChR expression was verified in each cell line using Western blot. Non-specific inhibition of nAChR demonstrated no consistent effect on preventing NIC induced resistance to CT, XRT, or CRT; however, specific inhibition of the alpha-3- or alpha-7-nAChR had variable cell specific ability to prevent NIC induced resistance. Inhibition of MAPK activity (using PD98059) produced marked reduction in proliferation of all cell lines, but generally had no effect on NIC induced resistance. PI3K inhibition (using LY294002) generally increased sensitivity to cisplatin and XRT; however, some PI3K activity was required to achieve the full effect of cisplatin. NIC prevented LY294002 induced sensitization to chemotherapy with no effect on sensitization to XRT. Conclusions: Nicotine induces a broad spectrum of resistance to CT, XRT, and CRT and serves as an excellent model of treatment resistance. Mechanisms of NIC induced resistance to CT and XRT appear to diverge. These findings have significant clinical implications including smoking cessation, treatment efficacy, and outcomes research in cancer patients. No significant financial relationships to disclose.

Geranyl Bearing Polyisoprenylated Benzoylphloroglucinol Derivatives from Hypericum sampsonii

Abstract Two new geranyl bearing polyisoprenylated benzoylphloroglucinol derivatives, hypersampsone G (1) and hypersampsone H (2) were isolated from the fruit of Hypericum sampsonii. Their structures were determined on the basis of spectroscopic data and the structure of 1 was confirmed by X-ray crystallographic analysis. Antitumor activities on A549 human cancer cells of the two compounds were tested.

Gadolinium texaphyrin (Gd-Tex)-malonato-platinum conjugates: Synthesis and comparison with carboplatin in normal and Pt-resistant cell lines

The synthesis of a new PEG-solubilized gadolinium texaphyrin (Gd-Tex) conjugate containing a malonate-Pt(NH(3))(2) moiety is described. The effect of the tumor localizing Gd-Tex macrocycle on platinum activity was evaluated in cell culture. The malonate moiety, analogous to that present in carboplatin, is expected to release an aquated Pt(NH(3))(2) species under physiological conditions. The half-life in phosphate-buffered saline was found to be ca. 3 days at room temperature, and the hydrolytic product released from the conjugate was collected and confirmed as Pt-based by flameless atomic absorption spectrophotometry. Anti-proliferative activity was tested using A549 human lung cancer and A2780 human ovarian cancer cell lines. In both cell lines, the activity of the Gd-Tex conjugate was found to be similar to that of carboplatin. Efficacy against a Pt-resistant ovarian cell line greater than that displayed by carboplatin was also observed.

Synthesis and Cytotoxicity of Bidesmosidic Betulin and Betulinic Acid Saponins

The naturally occurring cytotoxic saponin 28-O-beta-d-glucopyranosylbetulinic acid 3beta-O-alpha-l-arabinopyranoside (3) was easily synthesized along with seven bidesmosidic saponins starting from the lupane-type triterpenoids betulin (1) and betulinic acid (2). As highlighted by the preliminary cytotoxicity evaluation against A549, DLD-1, MCF7, and PC-3 human cancer cell lines, the bidesmosidic betulin saponin 22a, bearing alpha-l-rhamnopyranoside moieties at both C-3 and C-28 positions, was determined to be a potent cytotoxic agent (IC(50) 1.8-1.9 microM).

Propindilactones E−J, Schiartane Nortriterpenoids from Schisandra propinqua var. propinqua

Six new nortriterpenoids, propindilatones E-J (1-6), and two known (7, 8) schiartane-type nortriterpenoids were isolated from the stems of Schisandra propinqua var. propinqua. Their structures were elucidated by extensive spectroscopic analyses, and the structure of compound 4 was confirmed through single-crystal X-ray diffraction. The absolute configuration of compounds 1-3 was established using CD methods. Compounds 4-6 were noncytotoxic against K562, A549, and HT-29 human cancer cells.

Bcl-2 및 IAP family의 발현 변화와 caspase 활성을 통한 봉독의 인체폐암세포 apoptosis 유도

본 연구에서 봉독의 apoptosis 유도에 의한 항암기전 효능을 A549 인체폐암세포를 대상으로 조사하였으며, apoptosis 유발에 관여할 것으로 예상되는 중요한 유전자들의 발현 및 활성에 미치는 봉독의 영향을 조사하였다. A549 세포의 생존율은 봉독의 처리 농도 증가에 따라 강력하게 억제되었으며, 이는 염색질 응축 현상을 동반한 apoptosis 유발에 의한 것임을 알 수 있었다. 봉독 처리에 의한 apoptosis 유발은 Bax 및 Bcl-xL의 발현 변화 없이 Bcl-2의 발현 감소에 따른 상대적인 Bax의 발현 증가와 IAP family에 속하는 인자들의 발현 감소 및 caspase의 활성화와 연관성이 있었다. Bee venom is used to treat inflammatory diseases in Korean traditional medicine and has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in bee venom-induced apoptosis are still uncharacterized in human lung cancer cells. In the present study, we investigated the effects of bee venom on the apoptosis of A549 human lung epithelial cancer cells. Treatment of bee venom inhibited the cell viability and induced apoptosis in a concentration-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometry analysis. Bee venom-induced apoptosis in A549 cells was associated with a marked inhibition of anti-apoptotic Bcl-2 expression without significant changes in the levels of Bax and Bcl-xL. Bee venom treatment also inhibited the levels of IAP family members such as cIAP-1 and cIAP-2 and induced the proteolytic activation of caspase-3 and caspase-9. Although further studies are needed, the present results suggest that apoptotic signals evoked by bee vemon in A549 cancer cells may converge caspases activation through a down-regulation of Bcl-2 rather than an up-regulation of Bax. These findings provide important insights into the possible molecular mechanisms of the anti-cancer activity of bee vemon in human cancer cells.

Synthesis and anticancer activity of lipophilic platinum(II) complexes of 3,5-diisopropylsalicylate

Novel lipophilic platinum(II) complexes (LSPt-1–3), containing 3,5-diisopropylsalicylate (DIPS) as a leaving group and 2NH 3 or 1 R,2 R-diaminocyclohexane or (4 R,5 R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane as the carrier, have been synthesized, characterized and evaluated in vitro and in vivo. The octanol/water distribution coefficient of the complexes has also been measured. The results showed that the complexes achieved a typical square planar and the octanol/water distribution coefficient log P was 4.27, 4.37 and 4.31. The complexes were tested by SRB method to be more cytotoxic than Carboplatin, Oxaliplatin and Eptaplatin against 3AO, A549, NCI-H460 and SGC-7901 human cancer cell lines. Among complexes, LSPt-2 was much more effective than Carboplatin and Oxaliplatin in treating the NCI-H460 non-small-cell lung tumor-bearing mice. Its optimal activity was 38.8% ( T/ C) at a dose of 30 mg/kg following i.p. administration. LD 50 for the complex was found to be 230.9 mg/kg. LSPt-2 exhibited great anticancer activity, good lipophilic ability and low toxicity and therefore, it is a promising candidate for effective and stable pharmaceutical liposomal platinum anticancer drug.

Antioxidant Activities and Anticancer Cell Proliferation Properties of Wild Strawberries

Fruit extracts from 17 to 18 representatives of three strawberry species [Fragaria virginiana Mill., F. chiloensis (L.) Mill., and F. ×ananassa Duchesne ex Rozier] were tested for the ability to inhibit proliferation of A549 human lung epithelial cancer cells. The fruit extracts also were tested for activities against free radicals, (peroxyl radicals, hydroxyl radicals, singlet oxygen, and superoxide radicals), the activities of antioxidant enzymes [glutathione peroxidase (EC 1.11.1.9), superoxide dismutase (EC 1.15.1.1), guaiacol peroxidase (EC 1.11.1.7), ascorbate peroxidase (EC 1.11.1.11), monodehydroascorbate reductase (EC 1.6.5.4), dehydroascorbate reductase (EC 1.8.5.1), and glutathione reductase (EC 1.6.4.2)], and the activities of nonenzyme antioxidant components, ascorbic acid and glutathione. Correlations between the proliferation of cancer cells and these antioxidant activities were calculated. At the species level, F. virginiana fruit extract inhibited the proliferation of A549 human lung epithelial cancer cells to a significantly greater extent (34% inhibition) than the extracts from fruit of either F. chiloensis (26%) or F. ×ananassa (25%) (P < 0.0001). Extracts from fruit of F. virginiana also had significantly greater antioxidant activities and higher activities of antioxidant enzymes and nonenzyme components than did extracts from the other two species. Among individual genotypes, there was a high positive correlation between antiproliferation of A549 cancer cells, antioxidant activities against free radicals, activities of antioxidant enzymes, and activities of nonenzyme components. Although all fruit extracts from all the strawberry genotypes inhibited proliferation of A594 cancer cells, fruit extracts from seven F. virginiana genotypes showed significantly greater antiproliferative effects than any of the F. ×ananassa or F. chiloensis genotypes. These genotypes, CFRA 0982, JP 95-1-1, NC 95-19–1, RH 30, NC 96-48-1, JP 95-9-6, and LH 50-4, may be especially useful in developing cultivars with greater anticancer potential.

Upregulation of NAD(P)H:Quinone Oxidoreductase By Radiation Potentiates the Effect of Bioreductive β-Lapachone on Cancer Cells

We found that (β-Lapachone ((β-Lap), a novel bioreductive drug, caused rapid apoptosis, clonogenic cell death in A549 human lung epithelial cancer cells in vitro in a dose-dependent manner. The clonogenic cell death caused by (β-Lap could be significantly inhibited by dicoumarol, an inhibitor of NAD(P)H:quinone oxidoreductase (NO01), also by siRNA for NO01, demonstrating that N001-induced bioreduction of (β-Lap is an essential step in (β-Lap-induced cell death. Irradiation of A549 cells with 4 Gy caused a long-lasting upregulation of N001, thereby increasing N001mediated (β-Lap-induced cell deaths. Although the direct cause of (β-Lap-induced apoptosis is not yet clear, (β-Lap treatment reduced the expression of p53, NF-κB, whereas it increased cytochrome C release, caspase-3 activity, δ2AX foci formation. Importantly, (β-Lap treatment immediately after irradiation enhanced radiation-induced cell death, indicating that (β-Lap sensitizes cancer cells to radiation, in addition to directly killing some of the cells. The growth of A549 tumors induced in immunocompromised mice could be markedly suppressed by local radiation therapy when followed by (β-Lap treatment. This is the first study to demonstrate that combined radiotherapy, (β-Lap treatment can have a significant effect on human tumor xenografts.

Alboatisins A−C, ent-Atisene Diterpenoids from Isodon albopilosus

Three biogenetically interesting ent-kaurane-derived metabolites, alboatisins A-C (1-3), featuring a C-13-oxygenated ent-atisane skeleton, have been isolated from the aerial parts of Isodon albopilosus. Their structures were determined on the basis of spectroscopic evidence. Compound 2 exhibited cytotoxicity against A549 and HT-29 human cancer cells, with IC50 values of 8.3 and 7.9 microM, respectively.

Aurora kinase inhibition downregulates NF-κB and sensitises tumour cells to chemotherapeutic agents

We have identified that Aurora-A activates NF-κB via IκBα phosphorylation. Here, we analysed different human tumour cell types for their NF-κB activity. We found that there is an association between cell resistance to chemotherapeutic agents and NF-κB activation. A549 human lung adenocarcinoma cells and SKOV3 human ovarian cancer cells have high levels of NF-κB and are resistant to cytotoxic agents such as adriamycin and VP-16 (etoposide). We also found that in A549 and SKOV3 cells treated with a small molecule inhibitor towards Aurora kinases, the NF-κB activity was downregulated and the efficacy of cytotoxic drugs was enhanced. In addition, the transcriptional targets Bcl-X L and Bcl-2 were downregulated. This study provides evidence for a potential mechanism of chemoresistance and may be useful for the enhancement of certain chemotherapeutics regimens.

(172) Strawberries Inhibit Cancer Cell Proliferation

Representatives of three species of strawberries (Fragaria virginiana, F. chiloensis and F. ×ananassa) were evaluated for antioxidant capacity, scavenging capacity for reactive oxygen species (ROO·, ·OH, 1O2 and O2 .-), and inhibitory effect on proliferation of A549 human lung epithelial cancer cells. Differences among the strawberry genotypes were observed for all three qualities. High antioxidant and scavenging capacities were found in `CFRA 0982', `JP 95-1-1', NC 95-19-1 and RH 30. Lowest antioxidant and scavenging capacities were found in `Allstar'. There was also a relationship between scavenging capacity and the inhibition of cancer cell proliferation. The correlations (R2) between the scavenging capacities for the reactive oxygen species and the inhibition of cancer cell proliferation were 0.8074, 0.8279, 0.7862 and 0.7761 for ROO·, ·OH, 1O2 and O2.-, respectively. These results suggest that antioxidants, specifically their scavenging capacities, may play an important role in the antiproliferative activity of strawberries. This study also identified strawberry germplasm of value in developing cultivars useful for cancer prevention.

Antitumor agents 251: Synthesis, cytotoxic evaluation, and structure–activity relationship studies of phenanthrene-based tylophorine derivatives (PBTs) as a new class of antitumor agents

Polar phenanthrene-based tylophorine derivatives (PBTs) were designed, synthesized and evaluated as potential antitumor agents. These compounds contain a core phenanthrene structure and can be synthesized efficiently in excellent yield. The newly synthesized PBTs were evaluated for cytotoxic activity against the A549 human cancer cell line. Among them, N-(2,3-methylenedioxy-6-methoxy-phenanthr-9-ylmethyl)-l-2-piperidinemethanol (34) and N-(2,3-methylenedioxy-6-methoxy-phenanthr-9-ylmethyl)-5-aminopentanol (28) showed the highest potency with IC50 values of 0.16 and 0.27μM, respectively, which are comparable to those of currently used antitumor drugs. A structure–activity relationship (SAR) study was also explored to facilitate the further development of this new compound class.

New Cassaine Diterpenoid Amides with Cytotoxic Activities from the Bark ofErythrophleum fordii

A phytochemical investigation of the bark of Erythrophleum fordii led to six new cassaine diterpenoid amides (2, 4-8), together with two known compounds of the same skeleton, nor-cassamide ( 1) and nor-erythrosuamide (3). The structures were mainly established on the basis of 1D, 2D NMR and HR-MS analysis. The compounds 1, 2, 4, 6-8 exhibited selective cytotoxic activities (IC50 values < 10 microM) against A2780, KB, Bel-7402, BGC-823, MCF-7, HCT-8, Hela, PC-3M, A549 and Ketr3 human cancer cell lines in the MTT test.

Cytotoxic Prenylflavonoids from Artocarpus elasticus

Five new prenylated flavonoids, artelastoheterol (1), artelasticinol (2), cycloartelastoxanthone (3), artelastoxanthone (4), and cycloartelastoxanthendiol (5), along with five known compounds, were isolated from the root bark of Artocarpus elasticus. The structures of 1-5 were elucidated by spectroscopic methods and through comparison with data reported in the literature. The previously known compound artonol A (6) exhibited cytotoxic activity against the A549 human cancer cell line, with an ED50 value of 1.1 microg/mL.

Mechanisms of Cytotoxicity of Selected Organogold(III) Compounds

The effects of a few cytotoxic organogold(III) compounds on ovarian A2780 human cancer cells were investigated in comparison to cisplatin and oxaliplatin. The tested compounds produced significant antiproliferative effects and promoted apoptosis to a greater extent than platinum drugs while causing only modest cell cycle modifications. The mechanistic implications of these findings are discussed: mitochondrial pathways are proposed to be directly involved in the apoptotic process in relation to selective inhibition of thioredoxin reductase.

Synthesis and in vitro cytotoxicity of novel hydrophilic chiral 2-alkoxy-1,4-butanediamine platinum (II) complexes

Twenty-six new hydrophilic chiral 2-alkoxy-1,4-butanediamine platinum (II) complexes having a seven-membered ring structure between a bidentate carrier ligand and a platinum atom have been synthesized and most of them were evaluated for their in vitro cytotoxicity toward A549 human non-small cell lung carcinoma and HCT-116 human colon cancer cell lines. The cytotoxicities of platinum complexes are related to the nature of the carrier ligand and leaving group. Complex 5′b, viz. cis-dichloro[(2 R)-ethoxy-1,4-butanediamine] platinum (II), exhibits the greatest potency among those 21 tested platinum complexes in both cell lines.

Inhibition of Activator Protein-1, NF-κB, and MAPKs and Induction of Phase 2 Detoxifying Enzyme Activity by Chlorogenic Acid

Chlorogenic acid, the ester of caffeic acid with quinic acid, is one of the most abundant polyphenols in the human diet. The antioxidant and anticarcinogenic properties of chlorogenic acid have been established in animal studies. However, little is known about the molecular mechanisms through which chlorogenic acid inhibits carcinogenesis. In this study, we found that chlorogenic acid inhibited the proliferation of A549 human cancer cells in vitro. The results of the soft agar assay indicated that chlorogenic acid suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ cells in a dose-dependent manner. Pretreatment of JB6 cells with chlorogenic acid blocked UVB- or TPA-induced transactivation of AP-1 and NF-κB over the same dose range. At low concentrations, chlorogenic acid decreased the phosphorylation of c-Jun NH2-terminal kinases, p38 kinase, and MAPK kinase 4 induced by UVB/12-O-tetradecanoylphorbol-13-acetate, yet higher doses were required to inhibit extracellular signal-regulated kinases. Chlorogenic acid also increased the enzymatic activities of glutathione S-transferases (GST) and NAD(P)H: quinone oxidoreductase. Further studies indicated that chlorogenic acid could stimulate the nuclear translocation of Nrf2 (NF-E2-related factor) as well as subsequent induction of GSTA1 antioxidant response element (ARE)-mediated GST activity. The phosphatidylinositol 3-kinase pathway might be involved in the activation of Nrf2 translocation. These results provide the first evidence that chlorogenic acid could protect against environmental carcinogen-induced carcinogenesis and suggest that the chemopreventive effects of chlorogenic acid may be through its up-regulation of cellular antioxidant enzymes and suppression of ROS-mediated NF-κB, AP-1, and MAPK activation.

A549 폐암세포와 Sarcoma-180 복강암에 대한 인삼(人蔘) 증류약침(蒸溜藥鍼)의 영향에 관(關)한 실험적(實驗的) 연구(硏究)

A549 폐암세포와 Sarcoma-180 복강암에 대한 인삼(人蔘) 증류약침(蒸溜藥鍼)의 영향에 관(關)한 실험적(實驗的) 연구(硏究)