• Natural Product Sciences
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• 제28권3호
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• pp.121-129
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• 2022

Despite considerable efforts, cancer remains an aggressive killer worldwide. Chemotherapeutic drugs that are currently in use lead to destructive side effects and have not succeeded in fulfilling expectations. For centuries, medicinal plants are used for treating various diseases and are also known to have anticancer activity. The main aim of this research was to evaluate antiproliferative activity of saffron, clove, fenugreek, and green tea on Vero and MDA-MB-231 cell lines and to subsequently analyze the effect of these extracts on IRAK-4, TAK1, IKK-alpha, IKK-beta, NF-Kappa B, IRF3, IRF7 genes in Toll Like Receptors (TLRs) pathway. Antiproliferative assay was done by Neutral Red Dye uptake assay. Methanolic extract of green tea was found to be most effective against both cell lines as IC₅₀ was achieved at least concentration of the extract. For molecular studies, MDAMB-231 cells were sensitized with methanolic extract of green tea at same IC₅₀, and RT-PCR was performed to determine the relative expression of genes. Expression of IRAK-4, TAK1, IKK-beta, NF-Kappa B, IRF3 genes was down regulated and IRF7 and IKKalpha was upregulated. Green tea has a potential cytotoxic effect on both cell lines which was demonstrated by its effect on the expression of (TLRs) pathway genes.

• Clinical and Experimental Reproductive Medicine
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• 제48권4호
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• pp.322-336
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• 2021

Objective: Endometriosis is a chronic debilitating inflammatory condition characterized by the presence of endometrial tissues outside the uterine cavity. Pelvic soreness and infertility are the usual association. Due to the poor effectiveness of the hormone therapy and the high incidence of recurrence following surgical excision, there is no single effective option for management of endometriosis. Mesenchymal stem cells (MSCs) are multipotent stromal cells studied for their broad immunoregulatory and anti-inflammatory properties; however, their efficiency in endometriosis cases is still a controversial issue. Our study aim was to evaluate whether adipose tissue-derived MSCs (AD-MSCs) could help with endometriosis through their studied anti-inflammatory role. Methods: Female Wistar rats weighting 180 to 250 g were randomly divided into two groups: group 1, endometriosis group; established by transplanting autologous uterine tissue into rats' peritoneal cavities and group 2, stem cell treated group; treated with AD-MSCs on the 5th day after induction of endometriosis. The proliferative activity of the endometriosis lesions was evaluated through Ki67 staining. Quantitative estimation of interferon γ, tumor necrosis factor-α, interleukin (IL)-6, IL-1β, IL-10, and transforming growth factor β expression, as well as immunohistochemical detection of CD68 positive macrophages, were used to assess the inflammatory status. Results: The size and proliferative activity of endometriosis lesions were significantly reduced in the stem cell treated group. Stem cells efficiently mitigated endometriosis associated chronic inflammatory reactions estimated through reduction of CD68 positive macrophages and the expression of the proinflammatory cytokines. Conclusion: Stem cell therapy can be considered a novel remedy in endometriosis possibly through its anti-inflammatory and antiproliferative properties.

• Archives of Pharmacal Research
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• 제26권10호
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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.

• 대한두경부종양학회지
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• 제10권2호
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• pp.200-205
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• 1994

Proliferating cell nuclear antgen(PCNA) plays an important role in DNA synthesis in nucleoli and is highly conserved non-histone nuclear protein composed of 261 amino acid. and is considered to correlated with the cells proliferative state, because it is synthesized particulary during the proliferative period of late Gland S-phase. Therefore, PCNA index meaningfully increases in the active or proliferative kinetic cells. By the use of recently developed monoclonal antibodies against PCNA, the immunohistochemical staining methods can make possible. These staining methods are the useful and productive one for ascertaining the cell's proliferating abillity. Moreover, immunohistochemical staining method with a antiPCNA antibody has particulrar advantages as follows. By means of these methods, we can stain the tissue that was already fixed in formalin or paraffin wax. We can see with naked eye that which cell is, where is differentiated through a microscope. Lastly, it maintains the whole tissue architecture and makes a search for the correlation. As we have seen above, the immunohistochemical staining methods for PCNA have been studied as an impotant factor that can find the cell proliferative kinetics in malignancy and biologic behavior of tumors. To investigate of the proliferative activity in thyroid nodule, Authors evaluated cell proliferative activity by immunostaing for PNCA in 45 pathologically confirmed solitary thyroid nodule. The results were as follows. 1) The benign nodules were 25 cases(Adenomatous Goiter: 20 cases, Follicular adenoma: 5 cases) and malignant nodules were 20 cases(Papillary Ca : 14 cases, Follicular Ca : 4 cases, Anaplastic Ca : 2 cases). 2) The Most prevalent age groups were 4th decade(11 cases), and the next group was 5th decade. 3) The average PCNA labelling indices were as follows. Adenomatous goiter(I6.9%), Follicular adenoma(37.6%), papillary Ca(26.3%), Follicular Ca(8.8%) and Anaplastic Ca(86.7%). There were no significant differences in benign(20.4) and malignant nodules (28.8%) except anaplastic Ca(p=0.3226). 4) When the average tumor size 2cm in papillary Ca, the PCNA indices were 26.0% (below 2cm) : 26.6% (above 2cm) (p=0.9642). The PCNA incidies were 23.9% (with lymphatic spread) : 28.7% (without lymphatic spread) (p=0.7056). There were no signlficant differences in the above cases. In conclusion, there were no significant differences in cell proliferative activity by staining for PCNA between benign and malignat nodules except anaplastic Ca.

• Journal of Microbiology and Biotechnology
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• 제30권8호
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• pp.1214-1221
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• 2020

Esculetin 6-O-β-D-arabinofuranosyl-(1 → 6)-β-D-glucopyranoside (EAG) is a coumarin glycoside isolated from the stem bark of Fraxinus rhynchophylla. This study scrutinized the anti-proliferative activity of EAG on blood cancer-derived Jurkat leukemic cells. Cell viability assays in leukemic cancer cells determined that EAG possesses potent anti-proliferative effects. Moreover, treatment with EAG increased the proportion of apoptotic cells, resulted in cell cycle arrest being induced at the subG0/G1 phase, and reduced the proportion of cells present in the S phase. In addition, mitochondrial membrane potential was reduced by EAG in Jurkat cells. Additionally, EAG triggered apoptosis that was mediated by the downregulation of BCL-XL, p-IκBα, and p-p65 expressions in addition to the upregulation of cleaved Caspase 3 and BAX expressions. These findings revealed that the toxic effect of EAG was mediated by intracellular signal transduction pathways that involved a mechanism in which reactive oxygen species (ROS) were upregulated. Thus, this study concludes that EAG could potentially serve as a therapeutic agent for leukemia.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2307-2312
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• 2015

Curcumol is a sesquiterpene originally isolated from curcuma rhizomes, a component of herbal remedies commonly used in oriental medicine. Its beneficial pharmacological activities have attract significant interest recently. In this study, anti-cancer activity of curcumol was examined with both in vitro and in vivo models. It was found that curcumol exhibited time- and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses. Interestingly, curcumol did not display growth inhibition in MRC-5 human embryonic lung fibroblasts, suggesting the anti-proliferative effects of curcumol were specific to cancer cells. Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/ kg daily) significantly reduced tumor size without causing notable toxicity. In conclusion, curcumol appears a favorable anti-cancer candidate for further development.

• Biomolecules & Therapeutics
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• 제19권4호
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• pp.411-418
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• 2011

Ginsenoside Rp1 (G-Rp1) is a novel ginseng saponin derivative with anti-tumor activity. However, the biochemical and molecular mechanisms of G-Rp1 on anti-tumor activity are not fully understood. In the present study, we report that G-Rp1 inhibits lung cancer cell proliferation, migration and adhesion in p53 wild-type A549 and p53-defi cient H1299 cells. Anti-proliferative activity of G-Rp1 in lung cancer cells is mediated by enhanced nuclear localization of cyclin-dependent kinase inhibitors including $p27^{Kip1}$ and $p21^{WAF1/Cip1}$, and subsequent inhibition of pRb phosphorylation. We also show that these anti-tumor activities of G-Rp1 in both A549 and H1299 cells appear to be mediated by suppression of mitogenic signaling pathways such as ERK, Akt and $p70^{S6K}$. Taken together, these findings suggest further development and evaluation of G-Rp1 for the treatment of lung cancers with mutated p53 as well as wild-type p53.

• Biomolecules & Therapeutics
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• 제14권2호
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• pp.90-95
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• 2006

CKD-602 exerts its antitumor effect via inhibition of topoisomerase I in cancer cells. Multicellular spheroid (MCS) and Multicellular layers (MCLs) are known as in vitro 3-dimensional models which closely represent tumor conditions in vivo. In order to investigate the potential of CKD-602 against human colorectal tumors, we evaluated the anti-proliferative activity and penetration ability of CKD-602 in MCS and MCL cultures of DLD-l human colorectal cancer cells, respectively. The maximum effects($E_{max}$) induced by CKD-602 were significantly lower in MCS compared to monolayers (48% vs 92%). With prolonged drug exposure, the $IC_{50's}$ of CKD-602 decreased to $23.5{\pm}1.0nM$ in monolayers after 24 h exposure and $42.3{\pm}1.7nM$ in MCS after 6 days, respectively. However, no further increase in effect was observed for exposure time longer than growth doubling time (Td) in both cultures. Activity of CKD-602 was significantly reduced after penetration through MCL and also with cell-free insert membrane. In conclusion, CKD-602 showed significantly decreased anti-proliferative activity in 3D cultures (MCS) of human colorectal cancer cells. Tumor penetration of CKD-602 could not be determined due to loss of activity after penetration through cell free insert membrane, which warrants further evaluation using a modified model.

• 한국식품영양학회지
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• 제30권5호
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• pp.1127-1131
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• 2017

당조고추의 기능성 소재로서의 가능성을 알아보기 위하여 당조고추 70% 에탄올 추출물에 대한 항산화 활성 및 항암활성을 측정하였다. 당조고추 70% 에탄올 추출물의 총 폴리페놀은 30.29 mg GAE/g extract로 나타났다. 당조고추 70% 에탄올 추출물에 대한 DPPH radical 및 hydroxyl radical 소거활성을 $IC_{50%}$ 측정한 각각 2.87, 10.55 mg/mL의 소거활성을 보여 주었으며, ${\alpha}$-glucosidase 및 ${\alpha}$-amylase 저해활성은 10 mg/mL의 농도에서 각각 35.67, 58.41%로 나타났다. 당조고추 70% 에탄올 추출물에 대한 항암활성은 대장암 세포주의 0.5 mg/mL 농도에서 50% 암세포 성장억제를 보였지만, 다른 암세포에서는 억제효과를 나타내지 않았다.

• Preventive Nutrition and Food Science
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• 제11권4호
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• pp.268-272
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• 2006

Cimicifugae Rhizoma (CR) belongs to the Ranunculaceae family, which has been traditionally used to treat climacteric complaints, antipyretics and diaphoresis as an alternative medicine for estrogen hormone replacement therapy with estrogens. Recently, it has been reported that different extract fractions of CR have various effects such as anti-allergic, anti-inflammatory and anti-proliferative activities. The current study investigated the immunomodulatory effects of Cimicifugae Rhizoma water extracts (CRE) in the macrophage-like cell line, Raw 264.7. Our results showed that CRE ($1\sim50\;{\mu}g/mL$) stimulated tumoricidal activity and NO production, whereas phagocytic activity was inhibited at the same concentrations. Additionally, iNOS mRNA expression was significantly increased in Raw 264.7 exposed to CRE as demonstrated by RT-PCR. These results indicate that the tumoricidal activity induced by CRE may be mediated by the production of NO and these activities may be useful for the treatment of diseases such as cancer.