Natural product corynoline suppresses melanoma cell growth through inducing oxidative stress.
Chunyang YiXiaolong LiSi ChenMingyao LiuWeiqiang LuXiyun YePublished in: Phytotherapy research : PTR (2020)
Natural product corynoline is a unique isoquinoline alkaloid extracted from traditional Chinese medicine Corydalis bungeana Turcz, whereas its anticancer properties have not been investigated. In this study, we found that corynoline potently impairs the growth of melanoma cells, B16F10, and A375 in a concentration-dependent manner. Treatment of melanoma cells with corynoline results in G2 cell arrest accompanied by reduced cdc2 activation. Furthermore, corynoline triggers apoptosis of melanoma cells, which is associated with increased expression of Bax and cleaved caspase-3. Mechanistic study indicates that corynoline strongly induces reactive oxygen species (ROS) generation and subsequent DNA damage as evidenced by γ-H2AX accumulation. Notably, the effect of corynoline on melanoma cell cycle and apoptosis is abolished by a ROS scavenger N-acetyl cysteine (NAC), indicating a ROS-dependent mechanism. Finally, corynoline significantly inhibits in vivo B16F10 melanoma tumor growth accompanied by reduced expression of Ki-67 in tumor tissue. Taken together, our data suggest that corynoline suppresses melanoma cell growth in vitro and in vivo by inducing oxidative stress and represents a potential therapeutic agent for melanoma patients.
Keyphrases
- oxidative stress
- dna damage
- cell cycle
- reactive oxygen species
- cell death
- induced apoptosis
- poor prognosis
- skin cancer
- cell proliferation
- end stage renal disease
- endoplasmic reticulum stress
- diabetic rats
- cell cycle arrest
- dna repair
- signaling pathway
- chronic kidney disease
- ischemia reperfusion injury
- transcription factor
- mesenchymal stem cells
- single cell
- basal cell carcinoma
- cell therapy
- radiation therapy
- squamous cell carcinoma
- peritoneal dialysis
- newly diagnosed
- long non coding rna
- combination therapy
- single molecule
- pi k akt
- locally advanced
- heat shock protein
- heat stress
- rectal cancer