Sulfarotene Inhibits Colorectal Cancer via Mitigating Natural-Killer-Cell-Induced Stemness
Tumor cell stemness stands out as a pivotal factor driving tumor recurrence or metastasis and significantly contributes to the mortality of patients with colorectal cancer (CRC). Recent research has unveiled a link between immune-active cells and the induction of tumor cell stemness, ultimately lead...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/17/3/387 |
| _version_ | 1797239687363952640 |
|---|---|
| author | Keshu Hu Yu Dong Jiayu Zhang Mengling Liu Xun Sun Xin Cao Pengfei Zhang Tianshu Liu |
| author_facet | Keshu Hu Yu Dong Jiayu Zhang Mengling Liu Xun Sun Xin Cao Pengfei Zhang Tianshu Liu |
| author_sort | Keshu Hu |
| collection | DOAJ |
| description | Tumor cell stemness stands out as a pivotal factor driving tumor recurrence or metastasis and significantly contributes to the mortality of patients with colorectal cancer (CRC). Recent research has unveiled a link between immune-active cells and the induction of tumor cell stemness, ultimately leading to heightened resistance to treatment. In this study, stemness in CRC cell lines was assessed after co-culture with natural killer (NK) cells, both with and without sulfarotene administration. Furthermore, a CRC xenograft model was utilized to scrutinize the in vivo efficacy of sulfarotene in overcoming stemness induced by NK cell activation. As a result, CRC cells exhibited significant stemness after NK cell co-culture, as evidenced by the upregulation of several stemness markers associated with cancer stem cells. Moreover, these cells demonstrated remarkable resistance to commonly used chemotherapy agents for CRC, such as oxaliplatin and irinotecan. Importantly, sulfarotene effectively reversed the altered stemness of CRC cells in both in vitro and in vivo assays. In conclusion, sulfarotene emerges as a promising therapeutic strategy for overcoming colorectal cancer resistance to NK cells by effectively inhibiting stemness remodeling. This study underscores the potential of sulfarotene in augmenting NK-cell-mediated immune surveillance, proposing a novel immunotherapeutic approach against colorectal cancer. |
| first_indexed | 2024-04-24T17:55:30Z |
| format | Article |
| id | doaj.art-d1680340ce6a4b10b0f52d028d1476ca |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-04-24T17:55:30Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-d1680340ce6a4b10b0f52d028d1476ca2024-03-27T13:59:27ZengMDPI AGPharmaceuticals1424-82472024-03-0117338710.3390/ph17030387Sulfarotene Inhibits Colorectal Cancer via Mitigating Natural-Killer-Cell-Induced StemnessKeshu Hu0Yu Dong1Jiayu Zhang2Mengling Liu3Xun Sun4Xin Cao5Pengfei Zhang6Tianshu Liu7Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaTumor cell stemness stands out as a pivotal factor driving tumor recurrence or metastasis and significantly contributes to the mortality of patients with colorectal cancer (CRC). Recent research has unveiled a link between immune-active cells and the induction of tumor cell stemness, ultimately leading to heightened resistance to treatment. In this study, stemness in CRC cell lines was assessed after co-culture with natural killer (NK) cells, both with and without sulfarotene administration. Furthermore, a CRC xenograft model was utilized to scrutinize the in vivo efficacy of sulfarotene in overcoming stemness induced by NK cell activation. As a result, CRC cells exhibited significant stemness after NK cell co-culture, as evidenced by the upregulation of several stemness markers associated with cancer stem cells. Moreover, these cells demonstrated remarkable resistance to commonly used chemotherapy agents for CRC, such as oxaliplatin and irinotecan. Importantly, sulfarotene effectively reversed the altered stemness of CRC cells in both in vitro and in vivo assays. In conclusion, sulfarotene emerges as a promising therapeutic strategy for overcoming colorectal cancer resistance to NK cells by effectively inhibiting stemness remodeling. This study underscores the potential of sulfarotene in augmenting NK-cell-mediated immune surveillance, proposing a novel immunotherapeutic approach against colorectal cancer.https://www.mdpi.com/1424-8247/17/3/387colorectal cancernatural killer cellstemnesssulfarotene |
| spellingShingle | Keshu Hu Yu Dong Jiayu Zhang Mengling Liu Xun Sun Xin Cao Pengfei Zhang Tianshu Liu Sulfarotene Inhibits Colorectal Cancer via Mitigating Natural-Killer-Cell-Induced Stemness Pharmaceuticals colorectal cancer natural killer cell stemness sulfarotene |
| title | Sulfarotene Inhibits Colorectal Cancer via Mitigating Natural-Killer-Cell-Induced Stemness |
| title_full | Sulfarotene Inhibits Colorectal Cancer via Mitigating Natural-Killer-Cell-Induced Stemness |
| title_fullStr | Sulfarotene Inhibits Colorectal Cancer via Mitigating Natural-Killer-Cell-Induced Stemness |
| title_full_unstemmed | Sulfarotene Inhibits Colorectal Cancer via Mitigating Natural-Killer-Cell-Induced Stemness |
| title_short | Sulfarotene Inhibits Colorectal Cancer via Mitigating Natural-Killer-Cell-Induced Stemness |
| title_sort | sulfarotene inhibits colorectal cancer via mitigating natural killer cell induced stemness |
| topic | colorectal cancer natural killer cell stemness sulfarotene |
| url | https://www.mdpi.com/1424-8247/17/3/387 |
| work_keys_str_mv | AT keshuhu sulfaroteneinhibitscolorectalcancerviamitigatingnaturalkillercellinducedstemness AT yudong sulfaroteneinhibitscolorectalcancerviamitigatingnaturalkillercellinducedstemness AT jiayuzhang sulfaroteneinhibitscolorectalcancerviamitigatingnaturalkillercellinducedstemness AT menglingliu sulfaroteneinhibitscolorectalcancerviamitigatingnaturalkillercellinducedstemness AT xunsun sulfaroteneinhibitscolorectalcancerviamitigatingnaturalkillercellinducedstemness AT xincao sulfaroteneinhibitscolorectalcancerviamitigatingnaturalkillercellinducedstemness AT pengfeizhang sulfaroteneinhibitscolorectalcancerviamitigatingnaturalkillercellinducedstemness AT tianshuliu sulfaroteneinhibitscolorectalcancerviamitigatingnaturalkillercellinducedstemness |