Steroid receptor coactivators (SRC) are transcriptional coactivators. Among SRCs, SRC-3 is the most studied in relation to different types of tumors. However, the role of SRC-3 in early lung development and lung cancer has not been well studied. The expression profiles of SRC-3 showed that SRC-3 contributed to bronchial and alveolar development in embryonic lung development. SRC-3 was strongly expressed in Clara cells and type II alveolar cells during fetal lung development (E17.5- E18.5), and SRC-3 was expressed in both cell types in the adult lung. TTF-1 was expressed in the lungs of heterozygote SRC-3 mice and Clara cell-specific-CCSP-TAg tumor mice, along with SRC-3 expression. The expression of TTF-1 was localized at transformed Clara cells and multifocal adenocarcinomas in lung cancer mice. However, SRC-3 was not expressed in the multifocal adenocarcinomas, suggesting that SRC-3 might not be involved in the invasiveness of lung cancer. Cotransfection of TTF-1 in Clara cell-specific mtCC cell lines resulted in significant activation of CCSP expression. However, cotransfection of SRC-3 had no significant effects on transient transfection. These in vivo and in vitro results suggest that SRC-3 does not play a significant role in lung tumor progression. In conclusion, SRC-3 is involved in bronchial and alveolar development in fetal and adult lungs, but it does not play an important role in the progression of Clara cell-derived lung cancer.
Background: Proteases play a regulatory role in a variety of pathologies including cancer, pancreatitis, thromboembolic disorders, viral infections and many others. One of the possible strategies to combat these pathologies seems to be the use of protease inhibitors. LC-pi I, II, III and IV (Lavatera cashmerian-protease inhibitors) have been found in vitro to strongly inhibit trypsin, chymotrypsin and elastase, proteases contributing to tumour invasion and metastasis, indicated possible anticancer effects. The purpose of this study was to check in vitro anticancer activity of these four inhibitors on human lung cancer cell lines. Material and Methods: In order to assess whether these inhibitors induced in vitro cytoxicity, SRB assay was conducted with THP-1 (leukemia), NCIH322 (lung) and Colo205, HCT-116 (colon) lines. Results: LC-pi I significantly inhibited the cell proliferation of all cells tested and also LC-pi II was active in all except HCT-116. Inhibition of cell growth by LC-pi III and IV was negligible. $IC_{50}$ values of LC-pi I and II for NCIH322, were less compared to other cell lines suggesting that lung cancer cells are more inhibited. Conclusion: These investigations might point to future preventive as well as curative solutions using plant protease inhibitors for various cancers, especially in the lung, hence warranting their further investigation.
Cichello, Simon Angelo;Yao, Qian;Dowell, Ashley;Leury, Brian;He, Xiao-Qiong
Asian Pacific Journal of Cancer Prevention
/
v.16
no.11
/
pp.4781-4786
/
2015
Siberian ginseng (Eleutherococcus senticosus) is used primarily as an adaptogen herb and also for its immune stimulant properties in Western herbal medicine. Another closely related species used in East Asian medicine systems i.e. Kampo, TCM (Manchuria, Korea, Japan and Ainu of Hokkaido) and also called Siberian ginseng (Acanthopanax senticosus) also displays immune-stimulant and anti-cancer properties. These may affect tumour growth and also provide an anti-fatigue effect for cancer patients, in particular for those suffering from lung cancer. There is some evidence that a carbohydrate in Siberian ginseng may possess not only immune stimulatory but also anti-tumour effects and also display other various anti-cancer properties. Our study aimed to determine the inhibitory and also proliferative effects of a methanol plant extract of Siberan ginseng (E. senticosus) on various cancer and normal cell lines including: A-549 (small cell lung cancer), XWLC-05 (Yunnan lung cancer cell line), CNE (human nasopharyngeal carcinoma cell line), HCT-116 (human colon cancer) and Beas-2b (human lung epithelial). These cell lines were treated with an extract from E. senticosus that was evaporated and reconstituted in DMSO. Treatment of A-549 (small cell lung cancer) cells with E. senticosus methanolic extract showed a concentration-dependent inhibitory trend from $12.5-50{\mu}g/mL$, and then a plateau, whereas at 12.5 and $25{\mu}g/mL$, there is a slight growth suppression in QBC-939 cells, but then a steady suppression from 50, 100 and $200{\mu}g/mL$. Further, in XWLC-05 (Yunnan lung cancer cell line), E. senticosus methanolic extract displayed an inhibitory effect which plateaued with increasing dosage. Next, in CNE (human nasopharyngeal carcinoma cell line) there was a dose dependent proliferative response, whereas in Beas-2 (human lung epithelial cell line), an inhibitory effect. Finally in colon cancer cell line (HCT-116) we observed an initially weak inhibitory effect and then plateau.
Yun, Hee Jung;Jeoung, Da Jeoung;Jin, Soojung;Park, Jung-ha;Lee, Eun-Woo;Lee, Hyun-Tai;Choi, Yung Hyun;Kim, Byung Woo;Kwon, Hyun Ju
Journal of Microbiology and Biotechnology
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v.32
no.7
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pp.918-926
/
2022
Proteins related to DNA replication have been proposed as cancer biomarkers and targets for anticancer agents. Among them, minichromosome maintenance (MCM) proteins, often overexpressed in various cancer cells, are recognized both as notable biomarkers for cancer diagnosis and as targets for cancer treatment. Here, we investigated the activity of cedrol, a single compound isolated from Juniperus chinensis, in reducing the expression of MCM proteins in human lung carcinoma A549 cells. Remarkably, cedrol also strongly inhibited the expression of all other MCM protein family members in A549 cells. Moreover, cedrol treatment reduced cell viability in A549 cells, accompanied by cell cycle arrest at the G1 phase, and enhanced apoptosis. Taken together, this study broadens our understanding of how cedrol executes its anticancer activity while demonstrating that cedrol has potential application in the treatment of human lung cancer as an inhibitor of MCM proteins.
Objectives ; This study was to investigate the anti-cancer effects of herbal acupuncture with distilled fresh ginseng. The herbal acupuncture was injected to Chung-wan($C.V_{12}$) and Wisu($BL_{21}$) of mice that were subjected to Sarcoma-180 adbominal cancer cell and A549 human epithelial lung cancer cells in vitro. Methods : Anti-cancer effects of distilled fresh ginseng herbal acupuncture were tested by measruing Cox, Bcl-2, and Bax by using RT-PCR in A549 human epithelial lung cancer cells in vitro. And four weeks old Balb/c line male mice weighing around $20\;{\pm}\;3g$ were used to measure survival rate and anti-cancer effect to outputs of interleukin-2 and interleukin-4 using flow cytometry, possibility of mRNA menifestation using RT-PCR, and Cox mRNA. The results are as follows. Results : 1. In measuring mRNA menifestation in Cox, Bcl-2, and Bax by using RT-PCR in A549 human epithelial lung cancer cells in vitro, the result showed that fresh ginseng decreased Cox-2 which is directly involved in Inflammation process. 2. Survival rate was measured in an anti-cancer effect experiment against Sarcoma-180 abdorminal cancer. Median survival time of controlled group was 27 days, of experiment group I was 21 days, and of experiment group II was 27 days. Therefore, experiment group I showed -22.2% increase in survival rate and experiment group II showed no difference compare to controlled group. 3. There was no difference between condition group and controlled and experiment group in measuring outputs of interleukin-2 and interleukin 4 by using flow cytometry 4. In measuring outputs of interleukin-2 by using ELISA, there was no significant difference between condition group and controlled group and there was decrease in experiment group II compared to conditioned and controlled group. 5. In measuring cytokine mRNA menifestation by using RT-PCR, experiment group I showed increase of mRNA menifestation in interleukin-2,4 and $interferon-{\gamma}$ and experiment group II showed no significant difference in $interferon-{\gamma}$. Conclusion : According to the results, fresh ginseng herbal-acupuncture took a little effects in cancer. In using distilled fresh ginseng herbal acupuncture has effect on Cox-2 decrease. However, the difference in concentration of fresh ginseng showed no effect on killing cancer cell. It is assumed that inaccurate concentration of herbal acupuncture and fresh ginseng component could be the reason for this result. Therefore, future consideration will be studies on herbal acupuncture concentration.
Lee, Ung-Soo;Ban, Jung Ok;Yeon, Eung Tae;Lee, Hee Pom;Udumula, Venkatareddy;Ham, Young Wan;Hong, Jin Tae
Biomolecules & Therapeutics
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v.20
no.6
/
pp.538-543
/
2012
The Maillard Reaction Products (MRPs) are chemical compounds which have been known to be effective in chemoprevention. Death receptors (DR) play a central role in directing apoptosis in several cancer cells. In our previous study, we demonstrated that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal, a MRP product, inhibited human colon cancer cell growth by inducing apoptosis via nuclear factor-${\kappa}B$ (NF-${\kappa}B$) inactivation and $G_2$/M phase cell cycle arrest. In this study, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate, a new (E)-2,4-bis(p-hydroxyphenyl)-2-butenal derivative, was synthesized to improve their solubility and stability in water and then evaluated against NCI-H460 and A549 human lung cancer cells. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate reduced the viability in both cell lines in a time and dose-dependent manner. We also found that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate increased apoptotic cell death through the upregulation of the expression of death receptor (DR)-3 and DR6 in both lung cancer cell lines. In addition to this, the transfection of DR3 siRNA diminished the growth inhibitory and apoptosis inducing effect of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate on lung cancer cells, however these effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate was not changed by DR6 siRNA. These results indicated that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate inhibits human lung cancer cell growth via increasing apoptotic cell death by upregulation of the expression of DR3.
Cho, Young-Rak;Kim, Soo Hyeon;Yoon, Hyun Jae;Hong, Sam Yeol;Ko, Hee-Young;Park, Eun-Hee;Kim, Myoung-Dong;Seo, Dong-Wan
Food Engineering Progress
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v.15
no.1
/
pp.1-5
/
2011
Codonopsis lanceolata L. (Campanulaceae) has long been used in traditional Korean medicine to treat bronchitis, cough, and inflammatory diseases, however, the efficacy of anti-tumor activities remains to be defined. In this study the effects of Codonopsis lanceolata (C. lanceolata) on proliferation, migration and adhesion in lung (A549, H1299) and ovarian cancer (SKOV-3) cells were investigated. To assess and compare the pharmacological effects and production places of C. lanceolata, the ethanolic extracts of C. lanceolata from different places in Korea (Hongseong, Yecheon, Yeongwol, Yanggu, Gangjin, and Hoengseong) were prepared. The extract from Hoengseong county did have only marginal anti-proliferative activity in all the cell lines tested, however, other extracts had little or no effect on cell proliferation. The extracts from Hongseong, Gangjin or Hoengseong county had partial anti-migratory activity in lung cancer cells, but not in ovarian cancer cells. In addition, the extract from Hoengseong county had partial anti-adhesive activity in ovarian cancer cells, however, other extracts did not affect cell adhesion in both lung and ovarian cancer cells. Taken together, these findings provide the first description of anti-tumor efficacy of C. lanceolata from different production places in Korea, and suggest that C. lanceolata from Hoengseong county may have therapeutic potential in lung and ovarian cancers.
In humic substances, fulvic acid (FA) is a subclass of diverse compounds known as humic substances, which are by-products of organic degradation from microorganisms. FA can suppress the proliferation of tumor cells. Despite numerous studies, the exact mechanism for the various effects of FA is not clearly understood. Based on results demonstrating anti-proliferation effects on human cancer, we investigated whether FA has similar effects on lung cancer in this study. Firstly, the anti-cancer effect of FA in pulmonary epithelial tumor cell lines (TC-1 cells) was examined by confirming its inhibitory effect on the cell proliferation of TC-1 cells. TC-1 cell proliferation was reduced by FA on a dose-dependent and time-dependent manner. After 24 hours of FA treatment, cell morphological changes such as cell volume decrease, non-adherence and increased number of apoptotic cells were clearly observed. In addition, FA induced a DNA ladder pattern by increased of DNA fragments in TC-1 cells. In the intracellular regulatory pathway by FA, we confirmed that FA induced the reduction of the anti-apoptotic protein, Bcl-2 protein levels. These results indicate that FA has anticancer effect by inducing intracellular apoptotic pathway. Further research on the mechanism of anticancer effects will be basic data for the development of potential anticancer drugs.
Park, Hee-Bin;You, Ji-Eun;Kim, Pyung-Hwan;Kim, Keun-Sik
Biomedical Science Letters
/
v.27
no.1
/
pp.1-11
/
2021
Cancer stem cells, which are known to drive tumor formation and maintenance, are a major obstacle in the effective treatment of various types of cancer. Trans-membrane glycoprotein mucin 1 antigen and cell surface glycogen CD44 antigen are well-known surface markers of breast cancer cells and breast cancer stem cells, respectively. To effectively treat cancer cells and cancer stem cells, we developed a new drug-encapsulating liposome conjugated with dual-DNA aptamers specific to the surface markers of breast cancer cells and their cancer stem cells. These two aptamer (Apt)-targeted liposomes, which were prepared to encapsulate doxorubicin (Dox), were named "Dual-Apt-Dox". Dual-Apt-Dox is significantly more cytotoxic to both cancer stem cells and cancer cells compared to liposomes lacking the aptamers. Furthermore, we demonstrated the inhibitory efficacy of Dual-Apt-Dox against the experimental lung metastasis of breast cancer stem cells and cancer cells in athymic nude mice. We also showed the potent antitumor effects of dual-aptamer-conjugated liposome systems by targeting cancer cells as well as cancer stem cells. Thus, our data indicate that dual-aptamer-conjugated liposome systems can prove to be effective drug delivery vehicles for breast cancer therapy.
Turk, H. Mehmet;Camci, Celalettin;Sevinc, Alper;Bukyukberber, Suleyman;Sari, Ibrahim;Adli, Mustafa
Asian Pacific Journal of Cancer Prevention
/
v.13
no.1
/
pp.315-318
/
2012
Objective: Cyclooxygenase-2 (COX-2) has been claimed to play role in carcinogenesis and be related to a bad prognosis in tumours. The aim of this study was to investigate the relationship between COX-2 expression and clinical and pathological parameters in early and advanced stage lung cancer patients. Materials and Methods: A total of 73 patients with lung cancer (27 adenocarcinomas, 33 squamous cell carcinomas, 4 large cell carcinomas and 9 small cell cancer) were analysed retrospectively. COX-2 expression was evaluated by immunohistochemistry in resection materials or lung biopsies. Tumor cells demonstrating more intense staining than smooth muscle and endothelial cells were recorded as COX-2 positive. We investigated the correlation between increased COX-2 expression and histological type of the tumor, the stage of the disease and survival. Results: COX-2 expression was observed in 55% of the adenocarcinomas, 45% of the squamous cell carcinomas and 22% of the small cell carcinomas. No correlation was apparent between COX-2 expression and disease stage, histological type and the survival. Conclusion: The results of this study do not support COX-2 expression as an independent prognostic factor in lung cancer. However, since results of the literature are different, further studies made in larger series are needed.
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