Antiproliferative Activity of Krukovine by Regulating Transmembrane Protein 139 (TMEM139) in Oxaliplatin-Resistant Pancreatic Cancer Cells
Krukovine (KV) is an alkaloid isolated from the bark of <i>Abuta grandifolia</i> (Mart.) Sandw. (Menispermaceae) with anticancer potential in some cancers with <i>KRAS</i> mutations. In this study, we explored the anticancer efficacy and mechanism of KV in oxaliplatin-resista...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/9/2642 |
| _version_ | 1797602829051887616 |
|---|---|
| author | Jee-Hyung Lee Sang-Hyub Lee Sang-Kook Lee Jin-Ho Choi Seohyun Lim Min-Song Kim Kyung-Min Lee Min-Woo Lee Ja-Lok Ku Dae-Hyun Kim In-Rae Cho Woo-Hyun Paik Ji-Kon Ryu Yong-Tae Kim |
| author_facet | Jee-Hyung Lee Sang-Hyub Lee Sang-Kook Lee Jin-Ho Choi Seohyun Lim Min-Song Kim Kyung-Min Lee Min-Woo Lee Ja-Lok Ku Dae-Hyun Kim In-Rae Cho Woo-Hyun Paik Ji-Kon Ryu Yong-Tae Kim |
| author_sort | Jee-Hyung Lee |
| collection | DOAJ |
| description | Krukovine (KV) is an alkaloid isolated from the bark of <i>Abuta grandifolia</i> (Mart.) Sandw. (Menispermaceae) with anticancer potential in some cancers with <i>KRAS</i> mutations. In this study, we explored the anticancer efficacy and mechanism of KV in oxaliplatin-resistant pancreatic cancer cells and patient-derived pancreatic cancer organoids (PDPCOs) with <i>KRAS</i> mutation. After treatment with KV, mRNA and protein levels were determined by RNA-seq and Western blotting, respectively. Cell proliferation, migration, and invasion were measured by MTT, scratch wound healing assay, and transwell analysis, respectively. Patient-derived pancreatic cancer organoids (PDPCOs) with <i>KRAS</i> mutations were treated with KV, oxaliplatin (OXA), and a combination of KV and OXA. KV suppresses tumor progression via the downregulation of the Erk-RPS6K-TMEM139 and PI3K-Akt-mTOR pathways in oxaliplatin-resistant AsPC-1 cells. Furthermore, KV showed an antiproliferative effect in PDPCOs, and the combination of OXA and KV inhibited PDPCO growth more effectively than either drug alone. |
| first_indexed | 2024-03-11T04:22:02Z |
| format | Article |
| id | doaj.art-30bdc6fff7db4e2fbbacd5590630c6e6 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T04:22:02Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-30bdc6fff7db4e2fbbacd5590630c6e62023-11-17T22:42:35ZengMDPI AGCancers2072-66942023-05-01159264210.3390/cancers15092642Antiproliferative Activity of Krukovine by Regulating Transmembrane Protein 139 (TMEM139) in Oxaliplatin-Resistant Pancreatic Cancer CellsJee-Hyung Lee0Sang-Hyub Lee1Sang-Kook Lee2Jin-Ho Choi3Seohyun Lim4Min-Song Kim5Kyung-Min Lee6Min-Woo Lee7Ja-Lok Ku8Dae-Hyun Kim9In-Rae Cho10Woo-Hyun Paik11Ji-Kon Ryu12Yong-Tae Kim13Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaNatural Products Research Institute, Seoul National University College of Pharmacy, Seoul 08826, Republic of KoreaDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Biomedical Sciences, Korean Cell Line Bank, Laboratory of Cell Biology and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDxome Co., Ltd., Seongnam 331, Republic of KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaKrukovine (KV) is an alkaloid isolated from the bark of <i>Abuta grandifolia</i> (Mart.) Sandw. (Menispermaceae) with anticancer potential in some cancers with <i>KRAS</i> mutations. In this study, we explored the anticancer efficacy and mechanism of KV in oxaliplatin-resistant pancreatic cancer cells and patient-derived pancreatic cancer organoids (PDPCOs) with <i>KRAS</i> mutation. After treatment with KV, mRNA and protein levels were determined by RNA-seq and Western blotting, respectively. Cell proliferation, migration, and invasion were measured by MTT, scratch wound healing assay, and transwell analysis, respectively. Patient-derived pancreatic cancer organoids (PDPCOs) with <i>KRAS</i> mutations were treated with KV, oxaliplatin (OXA), and a combination of KV and OXA. KV suppresses tumor progression via the downregulation of the Erk-RPS6K-TMEM139 and PI3K-Akt-mTOR pathways in oxaliplatin-resistant AsPC-1 cells. Furthermore, KV showed an antiproliferative effect in PDPCOs, and the combination of OXA and KV inhibited PDPCO growth more effectively than either drug alone.https://www.mdpi.com/2072-6694/15/9/2642pancreatic cancerkrukovine<i>KRAS</i>transmembrane protein 139 (TMEM139)metastasispatient-derived pancreatic cancer organoid (PDPCO) |
| spellingShingle | Jee-Hyung Lee Sang-Hyub Lee Sang-Kook Lee Jin-Ho Choi Seohyun Lim Min-Song Kim Kyung-Min Lee Min-Woo Lee Ja-Lok Ku Dae-Hyun Kim In-Rae Cho Woo-Hyun Paik Ji-Kon Ryu Yong-Tae Kim Antiproliferative Activity of Krukovine by Regulating Transmembrane Protein 139 (TMEM139) in Oxaliplatin-Resistant Pancreatic Cancer Cells Cancers pancreatic cancer krukovine <i>KRAS</i> transmembrane protein 139 (TMEM139) metastasis patient-derived pancreatic cancer organoid (PDPCO) |
| title | Antiproliferative Activity of Krukovine by Regulating Transmembrane Protein 139 (TMEM139) in Oxaliplatin-Resistant Pancreatic Cancer Cells |
| title_full | Antiproliferative Activity of Krukovine by Regulating Transmembrane Protein 139 (TMEM139) in Oxaliplatin-Resistant Pancreatic Cancer Cells |
| title_fullStr | Antiproliferative Activity of Krukovine by Regulating Transmembrane Protein 139 (TMEM139) in Oxaliplatin-Resistant Pancreatic Cancer Cells |
| title_full_unstemmed | Antiproliferative Activity of Krukovine by Regulating Transmembrane Protein 139 (TMEM139) in Oxaliplatin-Resistant Pancreatic Cancer Cells |
| title_short | Antiproliferative Activity of Krukovine by Regulating Transmembrane Protein 139 (TMEM139) in Oxaliplatin-Resistant Pancreatic Cancer Cells |
| title_sort | antiproliferative activity of krukovine by regulating transmembrane protein 139 tmem139 in oxaliplatin resistant pancreatic cancer cells |
| topic | pancreatic cancer krukovine <i>KRAS</i> transmembrane protein 139 (TMEM139) metastasis patient-derived pancreatic cancer organoid (PDPCO) |
| url | https://www.mdpi.com/2072-6694/15/9/2642 |
| work_keys_str_mv | AT jeehyunglee antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT sanghyublee antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT sangkooklee antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT jinhochoi antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT seohyunlim antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT minsongkim antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT kyungminlee antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT minwoolee antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT jalokku antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT daehyunkim antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT inraecho antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT woohyunpaik antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT jikonryu antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells AT yongtaekim antiproliferativeactivityofkrukovinebyregulatingtransmembraneprotein139tmem139inoxaliplatinresistantpancreaticcancercells |