Related Experiment Video
Updated: Sep 29, 2025
Y-27632 Enriches the Yield of Human Melanocytes from Adult Skin Tissues
Published on: July 8, 2020
Novel chloroquine derivative suppresses melanoma cell growth by DNA damage through increasing ROS levels
Jiaoduan Li1,2,3,4, Jing Long1,2,3,4, Jianglin Zhang5
1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
Abstract:
Melanoma is a fatal cancer with a significant feature of resistance to traditional chemotherapeutic drugs and radiotherapy. A mutation in the kinase BRAF is observed in more than 66% of metastatic melanoma cases. Therefore, there is an urgent need to develop new BRAF-mutant melanoma inhibitors. High-dose chloroquine has been reported to have antitumour effects, but it often induces dose-limiting toxicity. In this study, a series of chloroquine derivatives were synthesized, and lj-2-66 had the best activity and was selected for further investigation. Furthermore, the anti-BRAF-mutant melanoma effect and mechanism of this compound were explored. CCK-8 and colony formation assays indicated that lj-2-66 significantly inhibited the proliferation of BRAF-mutant melanoma cells. Flow cytometry revealed that lj-2-66 induced G2/M arrest in melanoma cells and promoted apoptosis. Furthermore, lj-2-66 increased the level of ROS in melanoma cells and induced DNA damage. Interestingly, lj-2-66 also played a similar role in BRAF inhibitor-resistant melanoma cells. In summary, we found a novel chloroquine derivative, lj-2-66, that increased the level of ROS in melanoma cells and induced DNA damage, thus leading to G2/M arrest and apoptosis. These findings indicated that lj-2-66 may become a potential therapeutic drug for melanoma harbouring BRAF mutations.
Insights
A novel chloroquine derivative, lj-2-66, effectively inhibits BRAF-mutant melanoma by inducing cell cycle arrest and apoptosis. This compound shows promise as a therapeutic agent for melanoma, even in cases resistant to BRAF inhibitors.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Melanoma exhibits resistance to conventional therapies, necessitating novel treatment strategies.
- BRAF mutations are prevalent in metastatic melanoma, driving tumor growth and progression.
- Chloroquine shows anti-tumor effects but is limited by dose-limiting toxicities.
Purpose of the Study:
- To synthesize and evaluate novel chloroquine derivatives as potential BRAF-mutant melanoma inhibitors.
- To investigate the anti-melanoma efficacy and underlying mechanisms of the lead compound, lj-2-66.
- To assess the activity of lj-2-66 against BRAF inhibitor-resistant melanoma cells.
Main Methods:
- Synthesis and screening of chloroquine derivatives.
- Cell proliferation assays (CCK-8, colony formation).
- Flow cytometry for cell cycle analysis and apoptosis detection, ROS level measurement, and DNA damage assessment.
Main Results:
- lj-2-66 demonstrated significant inhibition of BRAF-mutant melanoma cell proliferation.
- lj-2-66 induced G2/M cell cycle arrest and promoted apoptosis in melanoma cells.
- lj-2-66 increased reactive oxygen species (ROS) levels and induced DNA damage, also effective in resistant cells.
Conclusions:
- The novel chloroquine derivative lj-2-66 exhibits potent anti-melanoma activity.
- lj-2-66 functions by inducing ROS, DNA damage, cell cycle arrest, and apoptosis.
- lj-2-66 represents a potential therapeutic candidate for BRAF-mutated melanoma, including resistant forms.
Related Concept Videos
01:35Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
02:23Abnormal Proliferation
01:30Skin Cancer
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...