Triptolide induces immunogenic cell death in cervical cancer cells via ER stress and redox modulation
Ziwen Zheng1,2, Yamei Chen2, Chao Wang2
1The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang 330006, Jiangxi, China.
Abstract:
Cervical cancer remains a significant global health burden, particularly in developing countries, despite advances in screening and prevention. Novel therapeutic strategies are urgently needed to improve outcomes for patients with advanced or metastatic disease. Triptolide (TL), a key component of the Chinese herb Tripterygium wilfordii, has shown potent anticancer effects in various malignancies. In this study, we investigated the anticancer effects of TL on cervical cancer cells in vitro and in vivo, focusing on its ability to induce immunogenic cell death (ICD). TL exhibited potent cytotoxicity, inhibited proliferation, induced apoptosis, and suppressed tumor growth in cervical cancer models. Mechanistically, TL induced ICD in cervical cancer cells, as evidenced by the calreticulin (CRT) exposure on the cell surface and the release of HMGB1 and ATP. TL-induced CRT exposure was mediated by endoplasmic reticulum (ER) stress, as demonstrated by the upregulation of ATF3 and the activation of oxidative stress and immune pathways. Oral administration of TL significantly inhibited tumor growth in a cervical cancer xenograft model, without overt toxicities. These findings highlight the potential of TL as a novel immunotherapeutic agent for cervical cancer and warrant further investigation into its clinical translation. The combination of TL with immune checkpoint inhibitors or other immunotherapies may provide a promising strategy to enhance the efficacy of cervical cancer treatment while minimizing adverse effects.
Insights
Triptolide (TL) shows potent anticancer effects against cervical cancer by inducing immunogenic cell death (ICD). This natural compound effectively inhibits tumor growth and may offer a new immunotherapeutic strategy for cervical cancer treatment.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Cervical cancer poses a significant global health challenge, especially in developing nations.
- Existing treatments for advanced or metastatic cervical cancer require novel therapeutic strategies.
- Triptolide (TL), derived from Tripterygium wilfordii, demonstrates broad-spectrum anticancer properties.
Purpose of the Study:
- To investigate the anticancer effects of Triptolide (TL) on cervical cancer cells.
- To explore TL's mechanism of action, focusing on the induction of immunogenic cell death (ICD).
- To evaluate TL's efficacy and safety in preclinical cervical cancer models.
Main Methods:
- In vitro assays assessing cytotoxicity, proliferation, and apoptosis.
- Analysis of ICD markers: calreticulin (CRT) exposure, HMGB1, and ATP release.
- In vivo studies using cervical cancer xenograft models with oral TL administration.
- Investigation of endoplasmic reticulum (ER) stress and immune pathway activation.
Main Results:
- TL demonstrated significant cytotoxicity, inhibited proliferation, and induced apoptosis in cervical cancer cells.
- TL successfully induced immunogenic cell death (ICD) via ER stress, evidenced by CRT exposure and HMGB1/ATP release.
- Oral administration of TL markedly suppressed tumor growth in vivo without significant toxicity.
- TL treatment activated oxidative stress and immune-related pathways.
Conclusions:
- Triptolide (TL) exhibits potent anticancer activity against cervical cancer through the induction of immunogenic cell death (ICD).
- TL demonstrates potential as a novel immunotherapeutic agent for cervical cancer, warranting further clinical investigation.
- Combination therapy with TL and immune checkpoint inhibitors may enhance treatment efficacy and minimize adverse effects.
More Related Videos
Related Concept Videos
01:17The Extrinsic Apoptotic Pathway
01:31The Intrinsic Apoptotic Pathway
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
01:27Tumor Immunotherapy