Related Experiment Video
Updated: Nov 19, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Identification of triptonide as a therapeutic agent for triple negative breast cancer treatment
Bowen Gao1, Jiongyu Chen2, Bingchen Han1
1Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Davis Building 2065, Los Angeles, CA, 90048, USA.
Abstract:
Triple-negative breast cancer (TNBC) is associated with a high rate of early recurrence and distant metastasis, frequent development of therapeutic resistance, and a poor prognosis. There is a lack of targeted therapies for this aggressive subtype of breast cancer. Identifying novel effective treatment modalities for TNBC remains an urgent and unmet clinical need. In this study, we investigated the anti-cancer effect of triptonide, a natural compound derived from the traditional Chinese medicinal herb Tripterygium wilfordii Hook F, in TNBC. We found that triptonide inhibits human TNBC cell growth in vitro and growth of TNBC xenograft mammary tumors. It induces apoptosis and suppresses stem-like properties as indicated by reduced mammosphere formation and aldehyde dehydrogenase activity in TNBC cells. We show that triptonide downregulates multiple cancer stem cell-associated genes but upregulates SNAI1 gene expression. In support of SNAI1 induction as a negative feedback response to triptonide treatment, in vitro-derived triptonide-resistant HCC1806 cells display a markedly higher expression of SNAI1 compared with parental cells. Mechanistically, the increase of SNAI1 expression is mediated by the activation of JNK signaling, but not by ERK and AKT, two well-established SNAI1 regulators. Furthermore, knockdown of SNAI1 in the triptonide-resistant HCC1806 cells increases sensitivity to triptonide and reduces mammosphere formation. These results indicate that triptonide holds promise as a novel anti-tumor agent for TNBC treatment. Our study also reveals a SNAI1-associated feedback mechanism which may lead to acquired resistance to triptonide.
Insights
Triptonide, a natural compound, effectively inhibits triple-negative breast cancer (TNBC) growth and stem-like properties. It also reveals a SNAI1 feedback mechanism potentially linked to acquired resistance in TNBC treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to high recurrence rates and resistance.
- A critical unmet need exists for novel, targeted therapies against this aggressive breast cancer subtype.
- Triptonide, a compound from Tripterygium wilfordii, is explored for its anti-cancer potential in TNBC.
Purpose of the Study:
- To investigate the anti-cancer effects of triptonide on triple-negative breast cancer (TNBC) cells and xenograft models.
- To elucidate the molecular mechanisms underlying triptonide's action, including its impact on cancer stem cell properties and gene expression.
- To identify potential resistance mechanisms, specifically the role of SNAI1 and JNK signaling.
Main Methods:
- In vitro cell culture assays to assess TNBC cell growth inhibition and apoptosis induction.
- In vivo xenograft studies to evaluate triptonide's effect on tumor growth.
- Analysis of cancer stem cell markers (mammosphere formation, aldehyde dehydrogenase activity) and gene expression (SNAI1, JNK, ERK, AKT).
- Development and characterization of triptonide-resistant cell lines to study resistance mechanisms.
Main Results:
- Triptonide demonstrated significant inhibition of TNBC cell proliferation and xenograft tumor growth.
- The compound suppressed stem-like properties in TNBC cells by reducing mammosphere formation and aldehyde dehydrogenase activity.
- Triptonide upregulated SNAI1 expression via JNK signaling activation, a mechanism implicated in acquired resistance.
- Knockdown of SNAI1 in resistant cells restored sensitivity to triptonide and reduced stem-like properties.
Conclusions:
- Triptonide exhibits promising anti-tumor activity against triple-negative breast cancer (TNBC), targeting both tumor growth and cancer stem cells.
- The study identified a novel SNAI1-mediated feedback mechanism involving JNK signaling that contributes to acquired resistance to triptonide.
- These findings suggest triptonide as a potential therapeutic agent for TNBC, with implications for managing treatment resistance.
More Related Videos
14:20Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
13:18Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma
Published on: March 3, 2023
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:15Drugs that Stabilize Microtubules