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  1. Article ; Online: Repositioning Trimebutine Maleate as a Cancer Treatment Targeting Ovarian Cancer Stem Cells

    Heejin Lee / Oh-Bin Kwon / Jae-Eon Lee / Yong-Hyun Jeon / Dong-Seok Lee / Sang-Hyun Min / Jun-Woo Kim

    Cells, Vol 10, Iss 918, p

    2021  Volume 918

    Abstract: The overall five-year survival rate for late-stage patients of ovarian cancer is below 29% due to disease recurrence and drug resistance. Cancer stem cells (CSCs) are known as a major contributor to drug resistance and recurrence. Accordingly, therapies ... ...

    Abstract The overall five-year survival rate for late-stage patients of ovarian cancer is below 29% due to disease recurrence and drug resistance. Cancer stem cells (CSCs) are known as a major contributor to drug resistance and recurrence. Accordingly, therapies targeting ovarian CSCs are needed to overcome the limitations of present treatments. This study evaluated the effect of trimebutine maleate (TM) targeting ovarian CSCs, using A2780-SP cells acquired by a sphere culture of A2780 epithelial ovarian cancer cells. TM is indicated as a gastrointestinal motility modulator and is known to as a peripheral opioid receptor agonist and a blocker for various channels. The GI50 of TM was approximately 0.4 µM in A2780-SP cells but over 100 µM in A2780 cells, demonstrating CSCs specific growth inhibition. TM induced G0/G1 arrest and increased the AV + /PI + dead cell population in the A2780-SP samples. Furthermore, TM treatment significantly reduced tumor growth in A2780-SP xenograft mice. Voltage gated calcium channels (VGCC) and calcium-activated potassium channels (BKCa) were overexpressed on ovarian CSCs and targeted by TM; inhibition of both channels reduced A2780-SP cells viability. TM reduced stemness-related protein expression; this tendency was reproduced by the simultaneous inhibition of VGCC and BKCa compared to single channel inhibition. In addition, TM suppressed the Wnt/β-catenin, Notch, and Hedgehog pathways which contribute to many CSCs characteristics. Specifically, further suppression of the Wnt/β-catenin pathway by simultaneous inhibition of BKCa and VGCC is necessary for the effective and selective action of TM. Taken together, TM is a potential therapeutic drug for preventing ovarian cancer recurrence and drug resistance.
    Keywords trimebutine maleate ; ovarian cancer stem cells ; BKCa channel ; Ca 2+ channel ; wnt/β-catenin signaling ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Effects of Complex Korean Medicine Treatment on a Patient with Knee Pain and Ankylosis Following a Distal Femur Osteotomy

    Han Bin Park / Eun Sil Heo / Dong Hwi Yoo / Won Suk Jang / Oh Bin Kwon / Ki Won Choi / Min Jin Kwon / Tae Ju Kim / Seon Woo Jang / Oh Hoon Kwon

    Journal of Acupuncture Research, Vol 39, Iss 2, Pp 134-

    A Case Report

    2022  Volume 138

    Abstract: Distal femur osteotomy (DFO) is a controlled surgical break of the femur performed to allow realignment of the limb. Redistribution of the load aims to correct the abnormal mechanical weight-bearing axes in patients with abnormal alignment of the lower ... ...

    Abstract Distal femur osteotomy (DFO) is a controlled surgical break of the femur performed to allow realignment of the limb. Redistribution of the load aims to correct the abnormal mechanical weight-bearing axes in patients with abnormal alignment of the lower extremities, and degenerative changes in the knee joint. This report describes a complex Korean medicine treatment for a patient complaining of knee pain and stiffness following a DFO. Post-operative care for the patient lasted 78 days with treatment including pharmacopuncture, acupuncture, herbal medicine, cupping therapy, and physiotherapy. The effectiveness of the treatments was evaluated using the numerical rating scale, range of motion of the knee, and by physical examination. After treatment, these evaluation indicators improved, suggesting that the complex Korean medicine treatment received by the patient was an appropriate treatment for knee pain and stiffness following a DFO.
    Keywords femur ; knee ; korean traditional medicine ; osteotomy ; pain ; pharmacopuncture ; Miscellaneous systems and treatments ; RZ409.7-999 ; Therapeutics. Pharmacology ; RM1-950
    Subject code 796
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher E-Tree Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Diethylstilbestrol, a Novel ANO1 Inhibitor, Exerts an Anticancer Effect on Non-Small Cell Lung Cancer via Inhibition of ANO1

    Yohan Seo / Sung Baek Jeong / Joo Han Woo / Oh-Bin Kwon / Sion Lee / Hye In Oh / Sungwoo Jo / Seon Ju Park / Wan Namkung / Uk Yeol Moon / Sungwoo Lee

    International Journal of Molecular Sciences, Vol 22, Iss 7100, p

    2021  Volume 7100

    Abstract: Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality; thus, therapeutic targets continue to be developed. Anoctamin1 (ANO1), a novel drug target considered for the treatment of NSCLC, is a Ca 2+ -activated chloride ... ...

    Abstract Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality; thus, therapeutic targets continue to be developed. Anoctamin1 (ANO1), a novel drug target considered for the treatment of NSCLC, is a Ca 2+ -activated chloride channel (CaCC) overexpressed in various carcinomas. It plays an important role in the development of cancer; however, the role of ANO1 in NSCLC is unclear. In this study, diethylstilbestrol (DES) was identified as a selective ANO1 inhibitor using high-throughput screening. We found that DES inhibited yellow fluorescent protein (YFP) fluorescence reduction caused by ANO1 activation but did not inhibit cystic fibrosis transmembrane conductance regulator channel activity or P2Y activation-related cytosolic Ca 2+ levels. Additionally, electrophysiological analyses showed that DES significantly reduced ANO1 channel activity, but it more potently reduced ANO1 protein levels. DES also inhibited the viability and migration of PC9 cells via the reduction in ANO1, phospho-ERK1/2, and phospho-EGFR levels. Moreover, DES induced apoptosis by increasing caspase-3 activity and PARP-1 cleavage in PC9 cells, but it did not affect the viability of hepatocytes. These results suggest that ANO1 is a crucial target in the treatment of NSCLC, and DES may be developed as a potential anti-NSCLC therapeutic agent.
    Keywords diethylstilbestrol ; anoctamin 1 ; inhibitor ; lung cancer ; apoptosis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  4. Article ; Online: A Retrospective Chart Review of 122 Inpatients with Knee Osteoarthritis Treated with Korean Medicine

    Dong-Hwi Yoo / Han-Bin Park / Won-Suk Jang / Oh-Bin Kwon / Ki-Won Choi / Yu-Jin Lee / Sang-Gun Lee / Jae-Yong Choi / Ho Kim / Seon-Woo Jang

    Journal of Acupuncture Research, Vol 38, Iss 3, Pp 205-

    An Analysis of the Effects of Treatment

    2021  Volume 218

    Abstract: Background Korean medicine treatment was assessed in patients with knee osteoarthritis (OA) according to subgroups of: sex, age, cause of knee OA, body mass index, hospitalization period, history, OA compartment, phenotype, and comorbidity. Methods A ... ...

    Abstract Background Korean medicine treatment was assessed in patients with knee osteoarthritis (OA) according to subgroups of: sex, age, cause of knee OA, body mass index, hospitalization period, history, OA compartment, phenotype, and comorbidity. Methods A retrospective review was performed of 122 inpatients who were admitted to the Hospital of Korean Medicine for Korean medicine treatment of knee pain, and were diagnosed with knee OA based on magnetic resonance imaging findings. Analysis of patient subgroups (sex, age, cause of knee OA, body mass index, hospitalization period, history, OA compartment, phenotype, and comorbidity) was carried out and treatments including acupuncture, cupping, pharmacopuncture, herbal medicine, chuna therapy, medicinal steaming therapy, manual therapy, and extracorporeal shock wave therapy were listed. The numeric rating scale (NRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 5-level EuroQol-5 Dimension (EQ-5D-5L) scores were measured before and after treatment to assess the effects of treatment on pain and quality of life. Results Seventeen males and 105 females were included in this study. Most patients were in their 60s. In the total study population, NRS, WOMAC, and EQ-5D-5L scores were improved statistically significant when comparing before and after treatment. The NRS and WOMAC scores improved statistically significant in the medial, patellofemoral, medial + patellofemoral, medial + lateral + patellofemoral compartment. Conclusion Korean medicine treatment significantly reduced pain, stiffness, and physical dysfunction, and improved the quality of life of patients with knee OA, suggesting that it may be an effective alternative to the current conservative treatments.
    Keywords acupuncture ; knee osteoarthritis ; korean traditional medicine ; pharmacopuncture ; Miscellaneous systems and treatments ; RZ409.7-999 ; Therapeutics. Pharmacology ; RM1-950
    Subject code 796
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher E-Tree Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  5. Article ; Online: Calcium Channels as Novel Therapeutic Targets for Ovarian Cancer Stem Cells

    Heejin Lee / Jun Woo Kim / Dae Kyung Kim / Dong Kyu Choi / Seul Lee / Ji Hoon Yu / Oh-Bin Kwon / Jungsul Lee / Dong-Seok Lee / Jae Ho Kim / Sang-Hyun Min

    International Journal of Molecular Sciences, Vol 21, Iss 7, p

    2020  Volume 2327

    Abstract: Drug resistance in epithelial ovarian cancer (EOC) is reportedly attributed to the existence of cancer stem cells (CSC), because in most cancers, CSCs still remain after chemotherapy. To overcome this limitation, novel therapeutic strategies are required ...

    Abstract Drug resistance in epithelial ovarian cancer (EOC) is reportedly attributed to the existence of cancer stem cells (CSC), because in most cancers, CSCs still remain after chemotherapy. To overcome this limitation, novel therapeutic strategies are required to prevent cancer recurrence and chemotherapy-resistant cancers by targeting cancer stem cells (CSCs). We screened an FDA-approved compound library and found four voltage-gated calcium channel blockers (manidipine, lacidipine, benidipine, and lomerizine) that target ovarian CSCs. Four calcium channel blockers (CCBs) decreased sphere formation, viability, and proliferation, and induced apoptosis in ovarian CSCs. CCBs destroyed stemness and inhibited the AKT and ERK signaling pathway in ovarian CSCs. Among calcium channel subunit genes, three L- and T-type calcium channel genes were overexpressed in ovarian CSCs, and downregulation of calcium channel genes reduced the stem-cell-like properties of ovarian CSCs. Expressions of these three genes are negatively correlated with the survival rate of patient groups. In combination therapy with cisplatin, synergistic effect was shown in inhibiting the viability and proliferation of ovarian CSCs. Moreover, combinatorial usage of manidipine and paclitaxel showed enhanced effect in ovarian CSCs xenograft mouse models. Our results suggested that four CCBs may be potential therapeutic drugs for preventing ovarian cancer recurrence.
    Keywords cancer stem cells ; cancer microenvironment ; stemness ; targeted treatment ; calcium channel blocker ; drug repositioning ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 572
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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