Abstract | BACKGROUND: METHODS: In the present study, we investigated the anti- cancer effect of the phytochemicals kaempferol (Kaem), genistein (Gen), and 3'3-diindolylmethane (DIM) on melanoma cell viability. We also evaluated the altered expression of cell cycle-related genes. We verified the production of intracellular reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress at both the protein and cellular level using a western blot, TUNEL assay, and Dihydrodichlorofluorescein diacetate (DCF-DA) assay. RESULTS: Treatment of A375SM melanoma cells with phytochemicals resulted in inhibition of cell growth. Treatment with phytochemicals increased the gene expression of p21 and decreased the gene expression of cyclin E and/or cyclin B. The three phytochemicals activated the ROS-p38-p53 apoptotic pathway by increasing the level of phosphorylated p38 MAPK and p53, and they activated the ER stress-mediated apoptotic pathway by increasing the level of phosphorylated eIF2α and C/EBP homologous protein (CHOP). Both the ROS-p38-p53 and ER stress-mediated pathway induced the mitochondrial apoptotic pathway by attenuating Bcl-2 expression and upregulating BAX. Detection of morphological changes demonstrated that Kaem and Gen can induce differentiation in A375SM cell line. CONCLUSION: These results indicate that phytochemicals are potentially useful in treatments for melanoma due to their ability to inhibit melanoma cell growth and division via the ROS and ER stress pathway.
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Authors | Jae-Rim Heo, Geum-A Lee, Gyu-Sik Kim, Kyung-A Hwang, Kyung-Chul Choi |
Journal | Phytomedicine : international journal of phytotherapy and phytopharmacology
(Phytomedicine)
Vol. 39
Pg. 100-110
(Jan 15 2018)
ISSN: 1618-095X [Electronic] Germany |
PMID | 29433671
(Publication Type: Journal Article)
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Copyright | Copyright © 2017 Elsevier GmbH. All rights reserved. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- Eukaryotic Initiation Factor-2
- Indoles
- Kaempferols
- Reactive Oxygen Species
- kaempferol
- Genistein
- p38 Mitogen-Activated Protein Kinases
- 3,3'-diindolylmethane
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Topics |
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects)
- Cell Differentiation
(drug effects)
- Cell Line, Tumor
- Endoplasmic Reticulum Stress
(drug effects)
- Eukaryotic Initiation Factor-2
(metabolism)
- Genistein
(pharmacology)
- Humans
- Indoles
(pharmacology)
- Kaempferols
(pharmacology)
- Melanoma
(drug therapy, metabolism, pathology)
- Mitochondria
(drug effects, metabolism)
- Phosphorylation
(drug effects)
- Reactive Oxygen Species
(metabolism)
- p38 Mitogen-Activated Protein Kinases
(metabolism)
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