ReferenceID 2124
Isolinderalactone sensitizes oxaliplatin-resistance colorectal cancer cells through JNK/p38 MAPK signaling pathways
Phytomedicine
Background: Isolinderalactone (ILL), a sesquiterpene lactone compound, can be extracted from the root of Lindera aggregate. Physiological activities of ILL, including anti-inflammatory and anti-proliferative effects, hav
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 2124
- Evidence Id
- 18714
- Core Evidence Id
- 18714
- Source Reference Id
- 4275
- Herb2 Reference Id
- HBREF005072
- Subject Paper Key
- HBIN030883_35987016
- Pubmed Id
- 35987016
- Doi
- 10.1016/j.phymed.2022.154383
- Paper Title
- Isolinderalactone sensitizes oxaliplatin-resistance colorectal cancer cells through JNK/p38 MAPK signaling pathways
- Paper Abstract
- Background: Isolinderalactone (ILL), a sesquiterpene lactone compound, can be extracted from the root of Lindera aggregate. Physiological activities of ILL, including anti-inflammatory and anti-proliferative effects, have been investigated in multiple diseases. Nevertheless, little is known regarding its anti-cancer activities and the mechanism of action of ILL in targeting human CRC cells. Purpose: To determine ILL-mediated anti-proliferative effects on oxaliplatin (Ox)-sensitive and resistant colorectal cancer (CRC) cells and underlying mechanisms involved in its effects focusing on signal transduction. Methods: Inhibitory effect of ILL on CRC cells was evaluated by analyzing mitochondrial membrane potential (MMP) dysfunction and multi-caspase activity. Apoptosis-regulating proteins and JNK/p38 signaling molecules were monitored by Western blotting. ROS-dependent physiological modifications by ILL were confirmed by pretreatment with N-acetylcysteine (NAC). Moreover, the involvement of JNK/p38 signaling in ROS-mediated apoptosis was verified by treatment with SP600125 (JNK inhibitor) and SB203580 (p38 inhibitor). Results: ILL decreased cell viability and colony formation in both CRC Ox-sensitive (HCT116 and HT29) and Ox-resistant (OxR) (HCT116-OxR and HT29-OxR) cells. ILL induced G2/M phase cell cycle arrest, ROS generation, phosphorylated (p)JNK/p38 MAPK activation, mitochondrial membrane potential (MMP) depolarization, and multi-caspase activation, which eventually triggered apoptotic cell death of CRC cells. In addition, combined treatment with ILL and SP600125, SB203580, or pan-caspase inhibitor (Z-VAD-FMK) prevented decreases in cell viability seen after treatment with ILL alone. Pretreatment with NAC attenuated ILL-mediated apoptosis, ROS production, and p-JNK/p38 expression. Conclusion: Taken together, our results suggest that ILL can exert its anticancer effect in CRC Ox-sensitive and OxR cells by inducing ROS-mediated apoptosis through JNK/p38 MAPK signaling pathways. This is the first study demonstrating that ILL has a potential to improve drug efficacy against resistance mechanisms, providing a new insight into therapeutic strategies targeting drug-resistant CRC.
- Journal
- Phytomedicine
- Publish Year
- 2022
- Experiment Subject
- human; crc cells; crc ox-sensitive; crc ox-sensitive and oxr cells; ox-resistant (oxr) (hct116-oxr and ht29-oxr) cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Colorectal Cancer; Drug-resistant Crc
- Paper Title Cn
- Paper Title En
- Isolinderalactone sensitizes oxaliplatin-resistance colorectal cancer cells through JNK/p38 MAPK signaling pathways
- Bilingual Status
- semi_complete