• Archives of Pharmacal Research
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• v.26 no.10
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• pp.832-839
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• 2003

Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and produce excessive amounts of nitric oxide (NO) and prostaglandin E$_2$ (PGE$_2$), which play key roles in the processes of inflammation and carcinogenesis. The root of Paeonia lactiflora Pall., and the root cortex of Paeonia suffruticosa Andr., are important Chinese crude drugs used in many traditional prescriptions. 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) is a major bioactive constituent of both crude drugs. PGG has been shown to possess potent anti-oxidant, anti-mutagenic, anti-proliferative and anti-invasive effects. In this study, we examined the inhibitory effects of 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) isolated from the root of Paeonia lactiflora Pall. on the COX-2 and iNOS activity in LPS-activated Raw 264.7 cells, COX-1 in HEL cells. To investigate the structure-activity relationships of gallate and gallic acid for the inhibition of iNOS and COX-2 activity, we also examined (-)-epigallocatechin gallate (EGCG), gallic acid, and gallacetophenone. The results of the present study indicated that PGG, EGCG, and gallacetophenone treatment except gallic acid significantly inhibited LPS-induced NO production in LPS-activated macrophages. All of the four compounds significantly inhibited COX-2 activity in LPS-activated macrophages. Among the four compounds examined, PGG revealed the most potent in both iNOS ($IC_{50}$ = 18 $\mu\textrm{g}/mL$) and COX-2 inhibitory activity (PGE$_2$: $IC_{50}$ = 8 $\mu\textrm{g}/mL$ and PGD$_2$: $IC_{50}$ = 12 $\mu\textrm{g}/mL$), respectively. Although further studies are needed to elucidate the molecular mechanisms and structure-activity relationship by which PGG exerts its inhibitory actions, our results suggest that PGG might be a candidate for developing anti-inflammatory and cancer chemopreventive agents.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7995-8001
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• 2014

Interferon-gamma (IFN-${\gamma}$) has been used to treat various malignant tumors. However, the molecular mechanisms underlying the direct anti-proliferative activity of IFN-${\gamma}$ are poorly understood. In the present study, we examined the in vitro antitumor activity of IFN-${\gamma}$ on two human non-small-cell lung carcinoma (NSCLC) cell lines, H322M and H226. Our findings indicated that IFN-${\gamma}$ treatment caused a time-dependent reduction in cell viability and induced apoptosis through a FADD-mediated caspase-8/tBid/mitochondria-dependent pathway in both cell lines. Notably, we also postulated that IFN-${\gamma}$ increased indoleamine 2,3-dioxygenase (IDO) expression and enzymatic activity in H322M and H226 cells. In addition, inhibition of IDO activity by the IDO inhibitor 1-MT or tryptophan significantly reduced IFN-${\gamma}$-induced apoptosis and death receptor 5 (DR5) expression, which suggests that IDO enzymatic activity plays an important role in the anti-NSCLC cancer effect of IFN-${\gamma}$. These results provide new mechanistic insights into interferon-${\gamma}$ antitumor activity and further support IFN-${\gamma}$ as a potential therapeutic adjuvant for the treatment of NCSLC.

• The Korean Journal of Food And Nutrition
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• v.30 no.5
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• pp.1127-1131
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• 2017

To evaluate the anti-oxidant and anti-tumor potential of the green pepper (Capsicum annuum L. cv. DangZo), total polyphenol content, radical scavenging activities and anti-tumor properties were measured. The total polyphenol content of the 70% ethanol extracts from green pepper (Capsicum annuum L. cv. DangZo) was 30.29 mg gallic acid equivalent/g extract. The DPPH radical and hydroxyl radical scavenging activities of 70% ethanol extracts of green pepper (Capsicum annuum L. cv. DangZo) were documented at 2.87 and 10.55, respectively. For ${\alpha}$-glucosidase and ${\alpha}$-amylase inhibitory activity, 70% ethanol extracts of green pepper (Capsicum annuum L. cv. DangZo) were documented at 35.67% and 58.41% respectively. The green pepper (Capsicum annuum L. cv. DangZo) demonstrated greater capability in terms of anti-neoplastic activity vis-a-vis colon cancer cell lines when compared to other cancer cell lines.s. er (Capsicum annuum L. cv. DangZo) higher activities of anticancer activities on colon cancer cell lines compared to other cancer cell lines.

• Journal of Life Science
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• v.28 no.9
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• pp.1022-1029
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• 2018

This study was carried out to search for the anti-inflammatory activities of ethanol extracts obtained from 5 kinds of oriental medical plant; Pleuropterus multiflorus extract (PME), Acorus calamus L. extract (ACE), Lithospermum erythrorhizon Siebold & Zucc. extract (LEE), Xanthium strumarium L. extract (XSE), Lonicera japonica extract (LJE), which have traditionally been used as a drug in oriental medical plants in Korea. XSE showed cytotoxicity at 100, $200{\mu}g/ml$ concentration in RAW264.7 cells (p<0.05) and ACE showed cytotoxicity at $200{\mu}g/ml$ concentration in RAW264.7 cells (p<0.05). But other oriental medical plants did not showed cytotoxicity was observed in RAW264.7 cells below $200{\mu}g/ml$ concentration. These extracts at non-toxic concentrations showed anti-inflammatory effects. PME, ACE, XSE and LJE showed a concentration-dependent inhibitory effect on NO production and $PGE_2$ production in LPS-induced RAW264.7 cells. In particular, XSE showed the highest NO production inhibition ($52.9{\mu}g/ml$, $IC_{50}$) as well as the highest $PGE_2$ production inhibition at $50{\mu}g/ml$ (73.6%). ACE and LEE showed cell proliferation effects on HaCaT keratinocyte cells. Especially, LEE showed 21.1, 53.5 and 99.6% proliferative activity by incubation for 1, 3, 5days at $100{\mu}g/ml$ concentration. ACE also showed 11.2, 26.0% proliferative activity for 1day and 3days at $10{\mu}g/ml$ concentration. As a result of this study, ethanol extracts obtained from 5 kinds of oriental medical plant showed anti-inflammatory activity and HaCaT cell regeneration effect.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6363-6367
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• 2013

Atractylis lancea (Thunb.) DC. (AL), an important medicinal herb in Asia, has been shown to have anti-tumor effects on cancer cells, but the involved mechanisms are poorly understood. This study focused on potential effects and molecular mechanisms of AL on the proliferation of the Hep-G2 liver cancer cell line in vitro. Cell viability was assessed by MTT test in Hep-G2 cells incubated with an ethanol extract of AL. Then, the effects of AL on apoptosis and cell cycle progression were determined by flow cytometry. Telomeric repeat amplification protocol (TRAP) assays was performed to investigate telomerase activity. The mRNA and protein expression of human telomerase reverse transcriptase (hTERT) and c-myc were determined by real-time RT-PCR and Western blotting. Our results show that AL effectively inhibits proliferation in Hep-G2 cells in a concentrationand time-dependent manner. When Hep-G2 cells were treated with AL after 48h,the $IC_{50}$ was about 72.1 ${\mu}g/mL$. Apoptosis was induced by AL via arresting the cells in the G1 phase. Furthermore, AL effectively reduced telomerase activity through inhibition of mRNA and protein expression of hTERT and c-myc. Hence, these data demonstrate that AL exerts anti-proliferative effects in Hep-G2 cells via down-regulation of the c-myc/hTERT/telomerase pathway.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.911-917
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• 2016

Lespedeza cuneata G. Don is an edible perennial herb used in traditional Korean medicine. We investigated the anti-proliferative properties and mechanism of L. cuneata extract. The ethanolic extract of L. cuneata dose-and time-dependently inhibited human colorectal cancer cell proliferation. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to test the effect of the extract on proliferation of HT-29 colorectal cancer cells. The extract inhibited HT-29 cell proliferation with an $IC_{50}$ value of $554.26{\pm}8.81{\mu}g/mL$. L. cuneata extract suppressed production of pro-inflammatory cytokines interleukin-6 and tumor necrosis $factor-{\alpha}$. Apoptosis was evaluated by analysis of DNA fragmentation, poly(ADP-ribose) polymerase cleavage, caspase-3 activity, and protein expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2). Our results demonstrated that the extract induced DNA fragmentation and characteristic morphological changes associated with apoptosis in HT-29 colorectal cancer cells. The extract also time- and dose-dependently up-regulated expression of the Bax and down-regulated expression of the Bcl-2. Furthermore, the extract dose- and time-dependently enhanced caspase-3 activity. Our findings provide evidence that L. cuneata extract may mediate its anti-proliferative effect via modulation of apoptosis.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.513-521
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• 1995

Background: Nucleolar organizer regions(NORs) are chromosomal segments encoding for ribosomal RNA and associated with argyrophilic nonhistone protein. Ribosomal RNA genes ultimately direct ribosome and protein synthesis, and it has been suggested the numbers of NORs detected in the cell may reflect nuclear and cellular activity. This study was performed to evaluate the applicability of AgNORs to the diagnosis of squamous cell carcinoma of the lung. Method: The one step silver methods(AgNORs) was used to stain NORs in the routinely processed, formalin fixed, paraffin embedded sections of 36 cases of squamous cell carcinoma of the lung obtained by surgical resection of primary tumor. In each specimen, 100 tumor cells and 100 normal cells adjacent to the tumor chosen at random were examined under an oil immersion lens at a magnification of ${\times}1000$. The mean number of AgNORs per nucleus was calculated for each specimen. Results: The mean number of AgNORs per nucleus(mAgNORs) of normal bronchial epithelium and squamous cell carcinoma of the lung was $1.74{\pm}0.25$ and $4.05{\pm}0.80$, respectively. The difference of mAgNOR between normal and tumor tissue was statistically significant(p<0.001). There was no statistical difference among tumors of different stages. The difference of mAgNOR between normal and tumor tissue was statistically significant in each TNM stage(p<0.05). Conclusion: Mean AgNOR count may be used as a useful marker for the differential diagnosis of benignancy and malignancy, and proliferative activity of the cell in squamous cell carcinoma of the lung. But there was no statistical difference in mean AgNOR count among tumors of different surgical stages. Further studies for the application of mAgNORs to the diagnosis of other histologic types and cytologic specimens of the lung cancer are needed.

• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.26-32
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• 2015

Objectives: Rheum undulatum L. has traditionally been used for the treatment of many diseases in Asia. However, its anti-proliferative activity in cancer has still not been studied. In the present study, we investigated the anti-cancer effects of methanol extract of Rheum undulatum L. (MERL) on human adenocarcinoma gastric cell lines (AGS). Methods: To investigate the anti-cancer effect of MERL on AGS cells, we treated the AGS cells with varying concentrations of MERL and performed 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Cell cycle analyses, measurements of the mitochondrial membrane potential (MMP), caspase activity assays and Western blots were conducted to determine whether AGS cell death occurred by apoptosis. Results: Treatment with MERL significantly inhibited growth of AGS cells in a concentration dependent manner. MERL treatment in AGS cells leaded to increased accumulation of apoptotic sub G1 phase cells in a concentration dependent manner. In control cultures, 5.38% of the cells were in the sub G1 phase. In MERL treated cells, however, this percentage was significantly increased (9.95% at $70{\mu}g/mL$, 15.94% at $140{\mu}g/mL$, 26.56% at $210{\mu}g/mL$ and 38.08% at $280{\mu}g/mL$). MERL treatment induced the decreased expression of pro-caspase-8 and -9 in a concentration dependent manner, whereas the expression of the active form of caspase-3 was increased. A subsequent Western blot analysis revealed increased cleaved levels of poly (ADP-ribose) polymerase (PARP) protein. Also, treatment with MERL increased the activities of caspase-3 and -9 compared with the control. MERL treatment increased the levels of the pro-apoptotic truncated Bid (tBid) and Bcl2 Antagonist X (Bax) proteins and decreased the levels of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein, whose is the stabilization of mitochondria. However, inhibitions of p38, extracellular signal regulated kinases (ERKs) and C-Jun N-terminal kinases (JNK) by MERL treatment did not affect cell death. Conclusion: These results suggest that MERL mediated cell death is associated with an intrinsic apoptotic pathway in AGS cells.

• Natural Product Sciences
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• v.29 no.2
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• pp.98-103
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• 2023

Sphaeranthus africanus is commonly used as a traditional remedy for sore throats and pain treatment in Vietnam. The aerial parts have been studied for its anti-inflammatory and anti-proliferative properties. However, the antioxidant and antidiabetic potential of the plant has not been explored. In this work, hydrophilic extracts of the plant's aerial parts were prepared in order to investigate its antioxidant and anti-diabetic properties. Also, the cytotoxicity of the root was evaluated and compared to that of the aerial parts. All of the extracts inhibited lipid peroxidation with IC₅₀ values ranging from 2.05 to 3.56 ㎍/mL, indicating substantial antioxidant activity. At an IC₅₀ value of 4.80 ㎍/mL, the 50% ethanol extract exhibited the most potent inhibition of α-glucosidase. The cytotoxic activity of root extracts is 2 to 5-fold less than that of the aerial parts. Nevertheless, dichloromethane and ethyl acetate extracts of the root demonstrated a selective effect on leukemia cells, with no harm towards the normal HEK-293 cell line. This work provides a scientific support for the antioxidant and antidiabetic activity of the plant. Hence, it may find a promising material for the development of novel antioxidant and antidiabetic agents. More research can be conducted on the phytochemistry and anticancer activities of the plant's root.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3735-3742
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• 2013

Background: Cardamom (Elettaria cardamom), also known as "Queen of Spices", has been traditionally used as a culinary ingredient due to its pleasant aroma and taste. In addition to this role, studies on cardamom have demonstrated cancer chemopreventive potential in in vitro and in vivo systems. Nevertheless, the precise poly-pharmacological nature of naturally occurring chemo-preventive compounds in cardamom has still not been fully demystified. Methods:In this study, an effort has been made to identify the proapoptopic, anti-inflammatory, anti-proliferative, anti-invasive and anti-angiogenic targets of Cardamom's bioactive principles (eucalyptol, alpha-pinene, beta-pinene, d-limonene and geraniol) by employing a dual reverse virtual screening protocol. Experimentally proven target information of the bioactive principles was annotated from bioassay databases and compared with the virtually screened set of targets to evaluate the reliability of the computational identification. To study the molecular interaction pattern of the anti-tumor action, molecular docking simulation was performed with Auto Dock Pyrx. Interaction studies of binding pose of eucalyptol with Caspase 3 were conducted to obtain an insight into the interacting amino acids and their inter-molecular bondings. Results:A prioritized list of target proteins associated with multiple forms of cancer and ranked by their Fit Score (Pharm Mapper) and descending 3D score (Reverse Screen 3D) were obtained from the two independent inverse screening platforms. Molecular docking studies exploring the bioactive principle targeted action revealed that H- bonds and electrostatic interactions forms the chief contributing factor in inter-molecular interactions associated with anti-tumor activity. Eucalyptol binds to the Caspase 3 with a specific framework that is well-suited for nucleophilic attacks by polar residues inside the Caspase 3 catalytic site. Conclusion:This study revealed vital information about the poly-pharmacological anti-tumor mode-of-action of essential oils in cardamom. In addition, a probabilistic set of anti-tumor targets for cardamom was generated, which can be further confirmed by in vivo and in vitro experiments.