• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6963-6966
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• 2015

Background: During the past few years, Hesa-A, a herbal-marine mixture, has been used to treat cancer as an alternative medicine in Iran. Based on a series of studies, it is speculated that Hesa-A possesses special cytotoxic effects on invasive tumors. To test this hypothesis, we investigated the selective anticancer effects of Hesa-A on several cancer cell lines with different metastatic potential. Materials and Methods: Hesa-A was prepared in normal saline as a stock solution of 10 mg/ml and further diluted to final concentrations of $100{\mu}/ml$, $200{\mu}g/ml$, $300{\mu}g/ml$ and $400{\mu}g/ml$. MTT-based cytotoxicity assays were performed with A549 (lung non small cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: All treated cancer cells showed significant (P<0.01) or very significant (P<0.0001) differences in comparison to negative control at almost all of the tested doses ($100-400{\mu}g/ml$). At the lower dose ($100{\mu}g/ml$), Hesa-A reduced cell viability to 66%, 45.3%, 35.5%, 33.2% in SKOV3, A549, PC-3 and MCF-7 cells, respectively. Moreover, at the highest dose ($400{\mu}g/ml$), Hesa-A resulted in 88.5%, 86.6%, 84.9% and 79.3% growth inhibition in A549, MCF-7, PC-3 and SKOV3 cells, respectively. Conclusions: Hesa-A exert potent cytotoxic effects on different human cancer cells, especially those with a high metastatic potential.

• Molecules and Cells
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• v.40 no.4
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• pp.291-298
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• 2017

MicroRNAs (miRNAs) are short non-coding RNAs that regulate genes posttranscriptionally. Past studies have reported that miR-210 is up-regulated in many cancers including cervical cancer, and plays a pleiotropic role in carcinogenesis. However, its role in regulating response towards anti-cancer agents has not been fully elucidated. We have previously reported that the natural compound 1'S-1'-acetoxychavicol acetate (ACA) is able to induce cytotoxicity in various cancer cells including cervical cancer cells. Hence, this study aims to investigate the mechanistic role of miR-210 in regulating response towards ACA in cervical cancer cells. In the present study, we found that ACA down-regulated miR-210 expression in cervical cancer cells, and suppression of miR-210 expression enhanced sensitivity towards ACA by inhibiting cell proliferation and promoting apoptosis. Western blot analysis showed increased expression of mothers against decapentaplegic homolog 4 (SMAD4), which was predicted as a target of miR-210 by target prediction programs, following treatment with ACA. Luciferase reporter assay confirmed that miR-210 binds to sequences in 3'UTR of SMAD4. Furthermore, decreased in SMAD4 protein expression was observed when miR-210 was overexpressed. Conversely, SMAD4 protein expression increased when miR-210 expression was suppressed. Lastly, we demonstrated that overexpression of SMAD4 augmented the anti-proliferative and apoptosis-inducing effects of ACA. Taken together, our results demonstrated that down-regulation of miR-210 conferred sensitivity towards ACA in cervical cancer cells by targeting SMAD4. These findings suggest that combination of miRNAs and natural compounds could provide new strategies in treating cervical cancer.

• The Journal of Internal Korean Medicine
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• v.23 no.2
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• pp.202-211
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• 2002

1. Background The previous studies on anticancer medicine derived from korean traditional medicine have focused on the life elongation of cancer cell bearing animals. However, it is thought that more molecular biological studies are needed to reveal their mechanism. 2. Objective The aim of this study was to investigate the molecular biological function of Sagunjatang plus Cremastrae Appenediculatae Tuber on cytostaticity, apoptosis and apoptosis related genes revelation against human stomach cancer cells(AGS). 3. Methods After administrating Sagunjatang and Sagunjatang plus Cremastrae Appenediculatae Tuber to human stomach cancer cell. MTT assay was performed to compare and examine the efficacy of each medicine on the cytostaticity of stomach cancer cells in proportion to time and doses, and apoptosis assay was performed to examine their effect on apoptosis by using DAPI dye and counting the number of cells which developed in an apoptotic body. In addition, the quantitative RT-PCR was used to examine their effect on the revelation of Bcl-2, Bax and P53, which are genes related to apoptosis. 4. Result and Conclusion Sagunjatang plus Cremastrae Appenediculatae Tuber demonstrated increased cytostaticity. decreased apoptosis and unremarkable revelation of apoptosis related genes. But in the cytostaticity and apoptosis, Sagunjatang plus Cremastrae Appenediculatae Tuber showed a tendency to control stomach cancer cells. Therefore, we can expect the clinical application to the related diseases. Besides, it needs another experiment on various cancer cells, such as, lung cancer cell and hysterocarcinoma cell.

• Molecules and Cells
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• v.37 no.7
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• pp.540-546
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• 2014

Several types of genetic and epigenetic regulation have been implicated in the development of drug resistance, one significant challenge for cancer therapy. Although changes in the expression of non-coding RNA are also responsible for drug resistance, the specific identities and roles of them remain to be elucidated. Long non-coding RNAs (lncRNAs) are a type of ncRNA (> 200 nt) that influence the regulation of gene expression in various ways. In this study, we aimed to identify differentially expressed lncRNAs in 5-fluorouracil-resistant colon cancer cells. Using two pairs of 5-FU-resistant cells derived from the human colon cancer cell lines SNU-C4 and SNU-C5, we analyzed the expression of 90 lncRNAs by qPCR-based profiling and found that 19 and 23 lncRNAs were differentially expressed in SNU-C4R and SNU-C5R cells, respectively. We confirmed that snaR and BACE1AS were down-regulated in resistant cells. To further investigate the effects of snaR on cell growth, cell viability and cell cycle were analyzed after transfection of siRNAs targeting snaR. Down-regulation of snaR decreased cell death after 5-FU treatment, which indicates that snaR loss decreases in vitro sensitivity to 5-FU. Our results provide an important insight into the involvement of lncRNAs in 5-FU resistance in colon cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5131-5136
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• 2012

Cancer is one of the major health problems worldwide and its current treatments have a number of undesired adverse side effects. Natural compounds may reduce these. Currently, a few plant products are being used to treat cancer. In this study, goniothalamin, a natural occurring styryl-lactone extracted from Goniothalamus macrophyllus, was investigated for cytotoxic properties against cervical cancer (HeLa), breast carcinoma (MCF-7) and colon cancer (HT29) cells as well as normal mouse fibroblast (3T3) using MTT assay. Fluorescence microscopy showed that GTN is able to induce apoptosis in HeLa cells in a time dependent manner. Flow cytometry further revealed HeLa cells treated with GTN to be arrested in the S phase. Phosphatidyl serine properties present during apoptosis enable early detection of the apoptosis in the cells. Using annexin V/PI double staining it could be shown that GTN induces early apoptosis on HeLa cells after 24, 48 and 72 h. It could be concluded that goniothalamin showing a promising cytotoxicity effect against several cancer cell lines including cervical cancer cells (HeLa) with apoptosis as the mode of cell death induced on HeLa cells by Goniothalamin was.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.427-436
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• 2012

Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction.Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product to be developed as not only the source of co-chemotherapeutic agents, but also phyto-estrogens. Therefore, further study needs to be conducted to explore the potential of citrus fruits in overcoming cancer.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.92-98
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• 2010

Breast cancer has been estimated as one of the most common causes of cancer death among women. The major cause of death from breast cancer is the metastatic spread of the disease from the primary tumor to distant sites in the body. Lycopene is one of the major carotenoids in fruits and vegetables including tomatoes. Epidemiological studies have shown that the dietary intake of lycopene is associated with decreased risk of cancer. Although mounting evidence shows the chemopreventive effect of lycopene, the role of lycopene in the prevention of metastatic potential of breast cancer has not been determined yet. In the present study, we investigated the inhibitory effect of lycopene on invasive and migratory phenotypes of two highly aggressive breast cancer cell lines, H-Ras-transformed MCF10A human breast epithelial cells (H-Ras MCF10A) and MDA-MB-231 human breast cancer cells. Here, we report that lycopene significantly inhibits invasion and migration as well as proliferation of H-Ras MCF10A and MDA-MB-231 cells. This study suggested an in vitro anti-cancer and anti-metastatic potential of lycopene. We also showed that activations of ERKs and Akt were inhibited by lycopene in H-Ras MCF10A cells, suggesting that the ERKs and Akt signaling pathways may be involved in lycopene-induced anti-proliferative and/or anti-invasive/migratory effects in these cells. Taken in conjunction with the fact that breast cancer metastasis is one of the most lethal malignancies in women, our findings may provide useful information for the application of lycopene in establishing strategy to prevent the metastatic breast cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.493-511
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• 2023

Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells. Silencing YAP under UA plus DIM conditions significantly increased the activation of the tumor suppressor PTEN in esophageal cancer cells, while decreasing p-Akt activation, indicating that the Akt signaling pathway could be down-regulated in esophageal cancer cells by targeting PTEN. Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.213-220
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• 2022

Although there have been advances in cancer therapy and surgical improvement, lung cancer has the lowest survival rate (19%) at all stages. This is because most patients are diagnosed with concurrent metastasis, which occurs due to numerous related reasons. Especially, lung cancer is one of the most common and malignant cancers in the world. Although there are advanced therapeutic strategies, lung cancer remains one of the main causes of cancer death. Recent work has proposed that epithelial-mesenchymal transition (EMT) is the main cause of metastasis in most cases of human cancers including lung cancer. EMT involves the conversion of epithelial cells, wherein the cells lose their epithelial abilities and become mesenchymal cells involved in embryonic development, such as gastrulation and neural crest formation. In addition, recent research has indicated that EMT contributes to altering the cancer cells into cancer stem cells (CSCs). Although EMT is important in the developmental stages, this process also activates lung cancer progression, including complicated and diverse signaling pathways. Despite the numerous investigations on signaling pathways involved in the progression of lung cancer, this malignancy is considered critical for treatment. EMT in lung cancer involves many transcription factors and inducers, for example, Snail, TWIST, and ZEB are the master regulators of EMT. EMT-related factors and signaling pathways are involved in the progression of lung cancer, proposing new approaches to lung cancer therapy. In the current review, we highlight the signaling pathways implicated in lung cancer and elucidate the correlation of these pathways, indicating new insights to treat lung cancer and other malignancies.

• The Korea Journal of Herbology
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• v.22 no.2
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• pp.65-72
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• 2007

Objectives : In this study, we investigate that Euphorbiae lathyridis Semen extract contributes to growth inhibitory effect and anti-cancer activity on the HT-29 human colon cancer cells. Methods : Euphorbiae lathyridis Semen was extracted from the Semen of the plant using 80% Methanol. The Euphorbiae lathyridis Semen extract was treated to different concentrations for 24 hr, 4Shr or 72hr. Growth inhibitory effect was analyzed by measuring FACS study and MTT assay. Cell apoptosis was confirmed by surveying caspases cascades activation using Westem blot. Results : Exposure to Euphorbiae lathyridis Semen extract (0.4mg/ml) results in an inhibitory effect on cell growth in HT-29 cells. Growth inhibition by Euphorbiae lathyridis Semen extract in HT-29 cells was related with the inhibition of proliferation and induction of apoptosis. The Euphorbiae lathyridis Semen extract induces DNA fragmentation in HT-29 cells. Furthermore, Euphorbiae lathyridis Semen extract induces cell apoptosis through the activation of caspases-3, caspase-9 and PARP cleavage. Conclusion : Euphorbiae lathyridis Semen extract induces apoptosis in human colon cancer cells, therefore, we suggest that Euphorbiae lathyridis Semen extract can be used as a novel class of anti-cancer drugs.