Melatonin Induces Autophagy via Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress Pathway in Colorectal Cancer Cells

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 16; p. 5038
• Main Authors: Chok, Kian Chung, Koh, Rhun Yian, Ng, Ming Guan, Ng, Pei Ying, Chye, Soi Moi
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 20-08-2021; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; Adenosine kinase; Adenosine monophosphate; AKT protein; Angiogenesis; Antioxidants; Apoptosis; Autophagy; Cancer therapies; Cell culture; Cell death; Chemotherapy; Colorectal cancer; colorectal cancer cells; Colorectal carcinoma; Cytotoxicity; Drug dosages; Endoplasmic reticulum; endoplasmic reticulum stress; Gene expression; Kinases; Melatonin; Oxidative stress; Phagocytosis; Protein kinase; Proteins; Quality of life; Rapamycin; reactive oxygen species; TOR protein; Tumors; Vacuoles
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26165038

Even though an increasing number of anticancer treatments have been discovered, the mortality rates of colorectal cancer (CRC) have still been high in the past few years. It has been discovered that melatonin has pro-apoptotic properties and counteracts inflammation, proliferation, angiogenesis, cell invasion, and cell migration. In previous studies, melatonin has been shown to have an anticancer effect in multiple tumors, including CRC, but the underlying mechanisms of melatonin action on CRC have not been fully explored. Thus, in this study, we investigated the role of autophagy pathways in CRC cells treated with melatonin. In vitro CRC cell models, HT-29, SW48, and Caco-2, were treated with melatonin. CRC cell death, oxidative stress, and autophagic vacuoles formation were induced by melatonin in a dose-dependent manner. Several autophagy pathways were examined, including the endoplasmic reticulum (ER) stress, 5′–adenosine monophosphate-activated protein kinase (AMPK), phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (Akt), and mammalian target of rapamycin (mTOR) signaling pathways. Our results showed that melatonin significantly induced autophagy via the ER stress pathway in CRC cells. In conclusion, melatonin demonstrated a potential as an anticancer drug for CRC.