Antitumor and apoptotic effects of quercetin on human melanoma cells involving JNK/P38 MAPK signaling activation

• Published in: European journal of pharmacology 2019-10, Vol.860, p.172568-172568, Article 172568
• Main Authors: Kim, Sung-Hyun, Yoo, Eun-Seon, Woo, Joong-Seok, Han, So-Hee, Lee, Jae-Han, Jung, Soo-Hyun, Kim, Hyeong-Jin, Jung, Ji-Youn
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antitumor; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Female; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; JNK/P38; MAP Kinase Signaling System - drug effects; Melanoma - pathology; Melanoma cells; Mice; p38 Mitogen-Activated Protein Kinases - metabolism; Quercetin; Quercetin - pharmacology; Xenograft Model Antitumor Assays
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2019.172568

In this study, we investigated whether Quercetin has anti-cancer effects on A375SM and A375P human melanoma cells. Cell viability was assessed using an MTT assay. The proliferation of melanoma cells was measured by a wound-healing assay. Quercetin significantly decreased viability and proliferation of A375SM cells in a concentration-dependent manner. However, quercetin had no effect on A375P cells. DAPI staining showed increased chromatin condensation in a concentration-dependent manner, indicating apoptosis. Flow cytometric analysis indicated that quercetin suppressed the viability of A375SM cells by inducing apoptosis. Expression of quercetin-induced apoptosis proteins was investigated by Western blot analysis. Quercetin increased the expression of Bax, phospho-JNK, phospho-p38 and phospho-ERK1/2, cleaved poly-ADP ribose polymerase and decreased Bcl-2 in a concentration-dependent manner. We also investigated the in vivo tumor-growth inhibitory effect of quercetin. Quercetin (at 50 and 100 mg/kg) significantly decreased the A375SM tumor volume compared to the control group and increased apoptosis as assessed by the TUNEL assay. Immunohistochemistry staining revealed that the level of phosphor-JNK and phosphor-p38 increased in the quercetin-treated mice. These results indicate that quercetin inhibited the growth of A375SM melanoma cells through apoptosis and thus can be regarded as a new and effective chemo-preventive or therapeutic agent. [Display omitted]