Abstract
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.
Highlights
IntroductionColorectal cancer (CRC) ranks third in incidence and second in cause of cancer death worldwide, with more than 1.9 million new cases and 935,000 deaths in the year 2020 [1]
Colorectal cancer (CRC) ranks third in incidence and second in cause of cancer death worldwide, with more than 1.9 million new cases and 935,000 deaths in the year 2020 [1].The number of deaths caused by CRC worldwide is predicted to increase to 2.5 million in the year 2035 [2]
The HT-29, SW48, and Caco-2 cells were treated for 72 h with various concentrations of melatonin (0.5, 1.0, 1.5, 2.0, and 2.5 mM) and with vehicle control
Summary
Colorectal cancer (CRC) ranks third in incidence and second in cause of cancer death worldwide, with more than 1.9 million new cases and 935,000 deaths in the year 2020 [1]. The number of deaths caused by CRC worldwide is predicted to increase to 2.5 million in the year 2035 [2]. The 5-year survival rate of CRC is around 90%, but it drops to around. New drugs against CRC have been developed in recent years, chemotherapy remains the mainstream of the first-line treatment [5]. Chemotherapy for CRC has undesirable side effects, which induce death of normal cells and reduce patients’ quality of life [6,7]
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