DNA strand intertwined with Tripterygium wilfordii plant, representing triptolide and cisplatin targeting DNA repair in triple-negative breast cancer cells.

Can Triptolide Boost Cisplatin's Fight Against Triple-Negative Breast Cancer?

Soraya Malik in Health & Wellness December 2025 • 4 min read.

"New research explores how combining triptolide with cisplatin could offer a more effective strategy against triple-negative breast cancer by targeting DNA repair mechanisms."

Breast cancer remains a significant health challenge for women worldwide, with incidence rates steadily increasing. Among the various subtypes, triple-negative breast cancer (TNBC) poses a unique challenge due to its lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression. This absence of common receptors means that targeted therapies are ineffective, leaving conventional chemotherapy as the primary treatment option.

Unfortunately, TNBC is notorious for developing resistance to chemotherapy, leading to poor clinical outcomes and aggressive tumor behavior. The urgent need for new strategies to overcome drug resistance and improve treatment efficacy has led researchers to explore novel therapeutic approaches.

One promising avenue involves the use of triptolide, a natural compound derived from the traditional Chinese medicine Tripterygium wilfordii. Triptolide has demonstrated anti-inflammatory and anti-tumor activities in various cancers. Researchers are now investigating its potential to enhance the effectiveness of existing chemotherapy drugs like cisplatin in treating TNBC.

How Triptolide Enhances Cisplatin's Effectiveness: Targeting DNA Repair

DNA strand intertwined with Tripterygium wilfordii plant, representing triptolide and cisplatin targeting DNA repair in triple-negative breast cancer cells.

Cisplatin, a platinum-based drug, is a cornerstone of chemotherapy for many cancers, including TNBC. It works by creating DNA crosslinks within cancer cells, which, if not repaired, can lead to cell death. However, TNBC cells often develop resistance to cisplatin by efficiently repairing the DNA damage, limiting the drug's effectiveness.

Triptolide's potential lies in its ability to interfere with the DNA repair mechanisms within TNBC cells. The study highlights that triptolide downregulates key proteins involved in DNA repair, specifically XRCC1 and PARP1. These proteins are crucial for base excision repair (BER) and single-strand break repair, pathways that TNBC cells utilize to overcome the DNA damage induced by cisplatin.

XRCC1 and PARP1: These proteins are essential for repairing single-strand breaks and base excision repair. By reducing their levels, triptolide hinders the cancer cells' ability to fix DNA damage.
RAD51: While triptolide also slightly decreases RAD51 levels, which is involved in homologous recombination, the primary impact appears to be on BER and single-strand break repair.
Sensitization to Cisplatin: By interfering with these repair mechanisms, triptolide makes TNBC cells more vulnerable to cisplatin's DNA-damaging effects.

The research indicates that when TNBC cells are exposed to triptolide, their ability to repair cisplatin-induced DNA damage is compromised, leading to increased cell death. This suggests that combining triptolide with cisplatin could overcome drug resistance and improve treatment outcomes in TNBC patients.

Future Implications: A New Approach to TNBC Therapy?

The study's findings suggest that triptolide could be a valuable addition to the treatment arsenal against TNBC. By targeting DNA repair mechanisms, triptolide enhances the effectiveness of cisplatin, potentially overcoming drug resistance and improving patient outcomes. Further research and clinical trials are needed to fully explore the potential of this combination therapy and to determine the optimal dosage and administration strategies. However, these findings offer a promising new avenue for combating this aggressive form of breast cancer.

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This article is based on research published under:

DOI-LINK: 10.1016/j.biopha.2018.11.008, Alternate LINK

Title: Triptolide Interferes With Xrcc1/Parp1-Mediated Dna Repair And Confers Sensitization Of Triple-Negative Breast Cancer Cells To Cisplatin

Subject: Pharmacology

Journal: Biomedicine & Pharmacotherapy

Publisher: Elsevier BV

Authors: Zhiwei Zhang, Caifeng Sun, Lu Zhang, Xinming Chi, Jiamei Ji, Xingjie Gao, Ying Wang, Zinan Zhao, Likun Liu, Xuejiao Cao, Yanqin Yang, Weifeng Mao

Published: 2019-01-01

Everything You Need To Know

What exactly is triple-negative breast cancer, and why is it so difficult to treat?

Triple-negative breast cancer (TNBC) is a subtype of breast cancer notable for lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2). This absence means that common targeted therapies aren't effective, making chemotherapy the primary treatment. TNBC is known for its aggressive behavior and tendency to develop resistance to chemotherapy, leading to poorer outcomes compared to other breast cancer subtypes. Research is focused on finding new ways to treat TNBC, especially methods that can overcome drug resistance.

What is Cisplatin, and how is it used to treat triple-negative breast cancer?

Cisplatin is a platinum-based chemotherapy drug used to treat various cancers, including triple-negative breast cancer (TNBC). It works by creating DNA crosslinks within cancer cells, which ideally leads to cell death. However, cancer cells, including TNBC cells, can develop resistance to Cisplatin by repairing the DNA damage it causes, reducing the drug's effectiveness. Strategies to enhance Cisplatin's impact, such as combining it with other compounds, are of great interest.

What is Triptolide, and why is it being studied in relation to triple-negative breast cancer?

Triptolide is a natural compound derived from the traditional Chinese medicine Tripterygium wilfordii. It has shown anti-inflammatory and anti-tumor activities in several cancers. In the context of triple-negative breast cancer (TNBC), Triptolide is being explored for its potential to enhance the effectiveness of chemotherapy drugs like Cisplatin by interfering with DNA repair mechanisms in cancer cells. This could help overcome drug resistance and improve treatment outcomes.

How does Triptolide boost the effectiveness of Cisplatin against triple-negative breast cancer?

Triptolide enhances Cisplatin's effectiveness in treating triple-negative breast cancer (TNBC) by interfering with DNA repair mechanisms within the cancer cells. Specifically, Triptolide downregulates key proteins involved in DNA repair, such as XRCC1 and PARP1, which are crucial for base excision repair (BER) and single-strand break repair. By hindering these repair processes, Triptolide makes TNBC cells more vulnerable to the DNA-damaging effects of Cisplatin, increasing cell death. While Triptolide also slightly decreases RAD51 levels, its primary impact is on BER and single-strand break repair.

What are XRCC1 and PARP1, and why are they important in the treatment of triple-negative breast cancer?

XRCC1 and PARP1 are proteins essential for DNA repair, specifically in base excision repair (BER) and single-strand break repair pathways. In the context of triple-negative breast cancer (TNBC) treatment, these proteins are significant because TNBC cells use them to repair DNA damage caused by chemotherapy drugs like Cisplatin, leading to drug resistance. By downregulating XRCC1 and PARP1, Triptolide interferes with the cancer cells' ability to fix DNA damage, making them more susceptible to Cisplatin's effects.