Melatonin induces cell apoptosis in Mia PaCa-2 cells via the suppression of nuclear factor-κB and activation of ERK and JNK: A novel therapeutic implication for pancreatic cancer.
Melatonin is synthesized by the pineal gland and is released into the blood. In the last several years, some studies have shown that melatonin has anticancer properties; however, the mechanisms behind the antitumour traits are unclear, especially in pancreatic cancer. Therefore, in the present study, we investigated the antitumour effects of melatonin on the human pancreatic carcinoma cell line MIA PaCa‑2 and explored its biological mechanisms. MIA PaCa‑2 cells were treated with melatonin, and we used a CCK‑8 assay to evaluate the cell viability. We also used flow cytometry to observe cell apoptosis and western blot analysis to assess the protein expression. Our study found that melatonin inhibited cell viability, suppressed colony formation and reduced cell migration and invasion and induced cell apoptosis in MIA PaCa‑2 cells. Our results showed that melatonin treatment inhibited NF‑κB p65 activation. Moreover, melatonin treatment activated the mitogen‑activated protein kinase pathways (c‑jun N‑terminal kinase and extracellular‑regulated kinase 1/2), which increased Bax protein expression and caspase‑3 cleavage and decreased Bcl‑2 protein expression. These new developments demonstrate that melatonin plays a potential role in anticancer treatment and may act as an effective therapeutic agent in the future.
Department of Gastroenterology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310000, P.R. China.
Weimin
W
Li
Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Jiansheng
J
Wu
Department of Gastroenterology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310000, P.R. China.
Zhiyin
Z
Li
Department of Infection, ZheJiang University International Hospital, Hangzhou, Zhejiang 310000, P.R. China.
Zhibo
Z
Zhou
Department of Endocrinology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Chao
C
Zheng
Department of Rehabilitation, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Le
L
Lin
Department of Gastroenterology, Taizhou Municipal Hospital, Taizhou, Zhejiang 318000, P.R. China.
Binbin
B
Tan
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Min
M
Huang
Department of Endocrinology, Zhejiang University International Hospital, Hangzhou, Zhejiang 310000, P.R. China.
Mengdi
M
Fan
D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008550:Melatonin / Q000008:administration & dosage*; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051996:Transcription Factor RelA / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D016328:NF-kappa B; C498143:RELA protein, human; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D008550:Melatonin