• Journal of Life Science
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• v.25 no.4
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• pp.441-449
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• 2015

Endlicheria anomala, a neotropical plant, is found in northern South America and the Amazon region. It is traditionally used to remove poisons and cure gangrene. According to recent data, this plant has diverse biological properties such as anti-oxidative, anti-inflammatory and anti-melanogenic properties. However, the anti-cancer effect of E. anomala and its molecular mechanisms remain unclear. In this study, we examined the anti-cancer effect and the active mechanism of methanol extract of E. anomala (MEEA) in human lung adenocarcinoma cells (A549) and human liver cancer cells (HepG2). Our data revealed that MEEA showed cytotoxic activity in a dose-dependent manner and induced apoptosis both in A549 and HepG2 cells. We verified evidences of apoptosis via formation of chromatin condensation, apoptotic body and accumulation of cells in the subG1 phase. Following observed apoptosis-related phenomena, we found that the induction of apoptosis by MEEA was associated with the increase of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) expression. Furthermore, MEEA-induced apoptosis was characterized with proteolytic activation of caspase-3, degradation of poly ADP ribose polymerase (PARP), and up-regulation of pro-apoptotic Bax expression. Taken together, these findings indicate that MEEA may have potential cancer therapeutic utility in A549 and HepG2 cells.

• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.345-349
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• 2015

Betulinic acid, a pentacyclic triterpene isolated from Jujube tree (Zizyphus jujuba Mill), has been known for a wide range of biological and medicinal properties such as antibacterial, antimalarial, anti-inflammatory, antihelmintic, antinociceptive, and anticancer activities. In the study, we investigated the antiviral activity on influenza A/PR/8 virus infected A549 human lung adenocarcinoma epithelial cell line and C57BL/6 mice. Betulinic acid showed the anti-influenza viral activity at a concentration of $50{\mu}M$ without a significant cytotoxicity in influenza A/PR/8 virus infected A549 cells. Also, betulinic acid significantly attenuated pulmonary pathology including increased necrosis, numbers of inflammatory cells and pulmonary edema induced by influenza A/PR/8 virus infection compared with vehicle- or oseltamivir-treated mice in vivo model. The down-regulation of IFN-${\gamma}$ level, which is critical for innate and adaptive immunity in viral infection, after treating of betulinic acid in mouse lung. Based on the obtained results, it is suggested that betulinic acid can be the potential therapeutic agent for virus infection via anti-inflammatory activity.

• Applied Biological Chemistry
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• v.51 no.3
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• pp.212-218
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• 2008

This study was performed to determine the antimutagenic and anticancer effects of ethanol extract of buckwheat sprout using Ames test and SRB assay, respectively. An ethyl acetate fraction (200 ${\mu}/plate$) from the ethanol extract of buckwheat sprout showed inhibition rate of 80.6% against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Salmonella typhimurium TA100 strain. Also the ethyl acetate fraction (200 ${\mu}/plate$) showed higher antimutagenic activity than other fractions against the mutagenesis induced by 4-nitroquinoline-1-oxide (4NQO) in Salmonella typhimurium TA98 and TA100. In addition, the ethyl acetate fraction (200 ${\mu}/plate$) showed high antimutagenic effect of 80.9% and 85.9% against the mutation of TA98 and TA100 strains induced by 3-amino-1,4-dimethyl-5H-pyrido-(4,3-b)indol (Trp-P-1), respectively. The cytotoxic effects of each solvent fraction from the ethanol extract of buckwheat sprout against human cancer cell lines including lung carcinoma (A549), gastric carcinoma (AGS), breast adenocarcinoma (MCF-7), hepatocellular carcinoma (Hep3B), and colon adenocarcinoma (Colo 205) were investigated. The ethyl acetate fraction of buckwheat sprout ethanol extract at the concentration of 1.0 mg/ml showed strong cytotoxic activities of 70.3, 94.8, 79.6, 82.3, and 73.2% against A549, AGS, MCF-7, Hep3B and Colo 205 cancer cell lines, respectively.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.161-166
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• 2014

Lung cancer is the most common causes of cancer-related deaths worldwide, and a lack of effective methods for early diagnosis has greatly impacted the prognosis and survival rates of the affected patients. Tumor-initiating cells (TICs) are considered to be largely responsible for tumor genesis, resistance to tumor therapy, metastasis, and recurrence. In addition to representing a good potential treatment target, TICs can provide clues for the early diagnosis of cancer. MicroRNA (miRNA) alterations are known to be involved in the initiation and progression of human cancer, and the detection of related miRNAs in TICs is an important strategy for lung cancer early diagnosis. As Hsa-miR-155 (miR-155) can be used as a diagnostic marker for non-small cell lung cancer (NSCLC), a smart molecular beacon of miR-155 was designed to image the expression of miR-155 in NSCLC cases. TICs expressing CD133 and CD338 were obtained from A549 cells by applying an immune magnetic bead isolation system, and miR-155 was detected using laser-scanning confocal microscopy. We found that intracellular miR-155 could be successfully detected using smart miR-155 molecular beacons. Expression was higher in TICs than in A549 cells, indicating that miR-155 may play an important role in regulating bio-behavior of TICs. As a non-invasive approach, molecular beacons could be implemented with molecular imaging to diagnose lung cancer at early stages.

• Journal of Pharmacopuncture
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• v.22 no.4
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• pp.269-278
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• 2019

Objectives: Naesohwangryeon-tang (NHT) is a type of traditional herbal formula, however, little is known about its antitumor activity. In this study, the antitumor properties of NHT was evaluated in human lung adenocarcinoma cells. Methods: To check the inhibitory effect of NHT, MTT assay was performed. Cell cycle analysis and detection of ROS production were conducted by flow cytometry. To evaluate the signaling pathway, Western blotting was conducted. Results: Our results showed that the decrease of cell proliferation by NHT stimulation occurred more significantly in A549 cells than in NCI-H460 cells. In addition, NHT-induced apoptosis was associated with the activation of caspases and production of reactive oxygen species (ROS). NHT-induced apoptosis was attenuated after pretreatments with z-VAD-fmk or N-acetylcysteine, suggesting that NHT-induced apoptosis was caspaseand ROS-dependent. Interestingly, NHT treatment led to the development of autophagic vesicular organelles and upregulation of several autophagy-related genes. The pretreatment of bafilomycin A1 decreased apoptosis slightly but increased cell viability in the presence of NHT. Conclusion: These findings indicated that NHT induces both apoptosis and cell-protective autophagy in human lung cancer cells. This data suggests that NHT might be a novel herbal drug for lung cancer.

• Molecules and Cells
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• v.41 no.8
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• pp.733-741
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• 2018

Mutations in spliceosome components have been implicated in carcinogenesis of various types of cancer. One of the most frequently found is U2AF1 S34F missense mutation. Functional analyses of this mutation have been largely limited to hematological malignancies although the mutation is also frequently seen in other cancer types including lung adenocarcinoma (LUAD). We examined the impact of knockdown (KD) of wild type (wt) U2AF1 and ectopic expression of two splice variant S34F mutant proteins in terms of alternative splicing (AS) pattern and cell cycle progression in A549 lung cancer cells. We demonstrate that induction of distinct AS events and disruption of mitosis at distinct sub-stages result from KD and ectopic expression of the mutant proteins. Importantly, when compared with the splicing pattern seen in LUAD patients with U2AF1 S34F mutation, ectopic expression of S34F mutants but not KD was shown to result in common AS events in several genes involved in cell cycle progression. Our study thus points to an active role of U2AF1 S34F mutant protein in inducing cell cycle dysregulation and mitotic stress. In addition, alternatively spliced genes which we describe here may represent novel potential markers of lung cancer development.

• Food Science and Preservation
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• v.11 no.2
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• pp.221-226
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• 2004

This study was carried out to determine the antimutagenic and anticancer effects of Allium victoriolis using Ames test and cytotoxicity. Allium victorialis extracted with ethanol and then further fractionated to chloroform, ethyl acetate and water. The inhibition rate of ethanol extract (200 $\mu\textrm{g}$/plate) of Allium victorialis in the Salmonella typhimurium TA100 strain showed 88.2% against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG). The suppression ratio against 4-nitroquinoline-1-oxide(4NQO) in the Salmonella typhimurium TA98 and TA100 strains showed 76.4% and 83.0%, respectively. The cytotoxicity effects of Allium victorialis extract against the cell lines with human lung carcinoma (A549), human breast adenocarcinoma (MCF-7) and human gastric cacinoma (KATOIII) were inhibited with the increase of extract concentration. The treatment of 0.5 $\mu\textrm{g}$/plate Allium victorialis of ethanol extract showed strong cytotoxicities of 74.2%, 71.3% and 67.4% against A549, MCF-7 and KATOIII, respectively.

• Journal of Life Science
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• v.31 no.2
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• pp.199-208
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• 2021

Euonymus porphyreus, a species of plant in the Celastraceae family, is widely distributed in East Asia, especially in Southern China. The botanical characteristics of E. porphyreus have been reported, but its antioxidative and anticancer activities remain unclear. In this study, we evaluated the antioxidative and anticancer effects of ethanol extracts of E. porphyreus (EEEP) and the molecular mechanism of its anticancer activity in human lung adenocarcinoma A549 cells. The total polyphenol and flavonoid compound contents from EEEP were 115.42 mg/g and 23.07 mg/g, respectively. EEEP showed significant antioxidative effects with a concentration at 50% of the inhibition (IC50) value of 11.09 ㎍/ml, as measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. EEEP showed cytotoxic activity by increasing the SubG1 cell population of A549 cells in a dose-dependent manner. Apoptosis in A549 cells treated with EEEP was evident due to increased apoptotic cells and apoptotic bodies, as detected by Annexin V and 4,6-diamidino-2-phenylindole (DAPI) staining, respectively. EEEP-induced apoptosis resulted in increased expression of the First apoptosis signal (Fas), p53, and Bax, with decreased expression of Bcl-2 and subsequent activation of caspase-8, -9, and caspase-3, leading to cleavage of poly (ADP-ribose) polymerase (PARP). Collectively, these results suggest that EEEP may exert an anticancer effect by inducing apoptosis in A549 cells through both intrinsic and extrinsic pathways.

• Journal of Life Science
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• v.29 no.6
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• pp.679-687
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• 2019

Litsea populifolia, a plant species of the Lauraceae family, is widely distributed in the tropical and subtropical areas of Asia. The phylogenetic relationships and botanical characteristics of L. populifolia have been reported; however, its anti-oxidative and anti-cancer activities remain unclear. In this study, we evaluated the anti-oxidative and anti-cancer effects of ethanol extracts of L. populifolia (EELP) together with the molecular mechanism of its anti-cancer activity in human lung adenocarcinoma A549 cells. EELP showed significant anti-oxidative effects with a 50% inhibitory concentration at $11.71{\mu}g/ml$, which was measured by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. EELP exhibited cytotoxic activity and induced cell cycle arrest at the G1 phase in A549 cells in a dose-dependent manner, whereas EELP did not have the cytotoxic effect on the normal human lung cell line IMR90. Treatment with EELP also resulted in a decreased expression of G1/S transition-related molecules-including cyclin-dependent kinase (CDK) 2, CDK6, cyclin D1, and cyclin E-both for the transcription and translation levels. EELP-induced G1 arrest was associated with the phosphorylation of checkpoint kinase 2 (CHK2), p53, cell division cycle 25 homolog A (CDC25A), and the reduction of CDC25A expression in A549 cells. Collectively, these results suggest that EELP may exert an anti-cancer effect by cell cycle arrest at the G1 phase through both p53-dependent and p53-independent (ATM/CHK2/CDC25A/CDK2) pathways in A549 cells.

• Journal of Life Science
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• v.25 no.9
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• pp.1051-1058
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• 2015

Citrus mutant fruits were induced by irradiation of citrus budsticks with 120 Gy of cobalt (⁶⁰CO) gamma irradiation. The citrus mutant inhibited the growth and induced apoptosis in various human cancer cells, including A549, HepG2, HCT116, MCF-7, and Hela. The results of a trypan blue exclusion assay showed that citrus mutant fruits exhibited excellent antiproliferation activity in various human cancer cells and low cytotoxicity in normal 16HBE140- and CHANG cells. In addition, the cell death induced by the citrus mutant fruits was associated with an increased population of cells in sub-G1 phase, and it caused DNA fragmentation in human lung adenocarcinoma A549 and hepatocellular carcinoma HepG2 cells. It also up-regulated the amount of cellular nitric oxide (NO^•) produced as a result of nitric oxide synthase (NOS) activation and suppressed the inhibitor of apoptosis protein (IAP) family in A549 and HepG2 cells. These findings indicate that the citrus mutant fruits activates the NO^•-mediated apoptotic pathway in A549 and HepG2 cells. It may merit further investigation as a potential chemotherapeutic and chemopreventive agent for the treatment of various types of cancer cells. The results provide important major new insights into the mechanisms of the anticancer activity of citrus mutant fruits.