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Novel chloroquine derivative suppresses melanoma cell growth by DNA damage through increasing ROS levels.
Li, Jiaoduan; Long, Jing; Zhang, Jianglin; Liu, Nian; Yan, Bei; Tang, Ling; Chen, Xiang; Peng, Cong.
Afiliação
  • Li J; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
  • Long J; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, China.
  • Zhang J; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, China.
  • Liu N; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
  • Yan B; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
  • Tang L; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, China.
  • Chen X; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, China.
  • Peng C; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
J Cell Mol Med ; 26(9): 2579-2593, 2022 05.
Article em En | MEDLINE | ID: mdl-35332658
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas B-raf / Melanoma Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas B-raf / Melanoma Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article