Abstract |
Ginsenoside Rk1 (Rk1) is a component found in processed ginseng that exhibits anti- insulin resistance, anti- inflammation and anti- cancer activities. However, there are few reports of Rk1 activity against triple negative breast cancer (TNBC). In this study, the anti-proliferation and potential mechanisms of Rk1 in MDA-MB-231 cells were investigated. Xenograft model exhibited that Rk1 significantly repressed tumor growth with low toxicity to major organs. Moreover, Rk1 dramatically inhibited cell proliferation, colony formation, promoted LDH release, and induced G0/G1 phase arrest. Rk1 also triggered intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential reduction. Western blot results revealed that Rk1 increased the expression of Bax, cytochrome C, cleaved caspase 3, 8 and 9 levels and decreased Bcl-2 level and blocked the PI3K/Akt pathway. Pretreatment with the pan- caspase inhibitor Z-VAD-FMK, PI3K/Akt pathway activator insulin or ROS scavenger N-acetylcysteine (NAC) further demonstrated that ROS/PI3K/Akt pathway was responsible for Rk1-induced apoptosis. Overall, this is the first study to illustrate the anti- triple negative breast cancer effects and mechanisms of Rk1 and ginsenoside Rk1 could be a new promising anti- tumor drug for TNBC.
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Authors | Yinan Hong, Daidi Fan |
Journal | Toxicology
(Toxicology)
Vol. 418
Pg. 22-31
(04 15 2019)
ISSN: 1879-3185 [Electronic] Ireland |
PMID | 30797898
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2019 Elsevier B.V. All rights reserved. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- Apoptosis Regulatory Proteins
- Ginsenosides
- Reactive Oxygen Species
- ginsenoside Rk1
- Phosphatidylinositol 3-Kinase
- Proto-Oncogene Proteins c-akt
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Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects)
- Apoptosis Regulatory Proteins
(metabolism)
- Cell Cycle Checkpoints
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Female
- Ginsenosides
(pharmacology)
- Humans
- Membrane Potential, Mitochondrial
(drug effects)
- Mice, Inbred BALB C
- Mice, Nude
- Mitochondria
(drug effects, metabolism, pathology)
- Phosphatidylinositol 3-Kinase
(metabolism)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Reactive Oxygen Species
(metabolism)
- Signal Transduction
- Triple Negative Breast Neoplasms
(drug therapy, metabolism, pathology)
- Xenograft Model Antitumor Assays
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