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Review Open Access

Ursolic acid: A natural pentacyclic triterpenoid with clinical promise in gynecological and breast cancers (Review)

  • Authors:
    • Tingting Chen
    • Shirun Sun
    • Zhengli Zhou
    • Xiuqin Zhang
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    Affiliations: Jimo District Qingdao Hospital of Traditional Chinese Medicine, Qingdao, Shandong 266200, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 153
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    Published online on: September 11, 2025
       https://doi.org/10.3892/or.2025.8986
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Abstract

Gynecological and breast cancers pose significant challenges to women's health worldwide. Despite notable advancements in diagnosis and treatment, they remain leading causes of cancer‑related mortality. Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid widely found in plants, has garnered considerable attention due to its diverse pharmacological activities. It has been demonstrated that UA exhibits a range of biological effects, including antitumor, anti‑inflammatory, and antioxidant properties, with particularly promising therapeutic potential in breast and gynecological cancers. UA exerts its anticancer effects by modulating multiple signaling pathways, such as PI3K/AKT, NF‑κB, and Wnt/β‑catenin, thereby effectively inhibiting tumor cell proliferation, inducing apoptosis, reversing chemoresistance, and suppressing cancer stem cell characteristics. When combined with chemotherapeutic agents such as cisplatin and doxorubicin, UA not only enhances antitumor efficacy but also mitigates the adverse effects associated with chemotherapy. The present review summarizes the recent research progress and underlying mechanisms of UA in the treatment of gynecological and breast cancers, aiming to provide valuable insights for researchers and clinicians in the field.
View Figures

Figure 1

UA exerts multifaceted antitumor
effects against ovarian cancer. It induces apoptosis and cell cycle
arrest by activating the caspase cascade, modulating the Bax/Bcl-2
ratio, and inhibiting the PI3K/AKT and GSK-3β/β-catenin pathways.
UA also suppresses glycolysis and metabolic reprogramming by
targeting KLF5 and downstream PI3K/AKT signaling. When combined
with chemotherapeutic agents such as cisplatin and doxorubicin, UA
enhances efficacy while reducing toxicity and reversing drug
resistance through regulation of HuR/MDR1 expression. Additionally,
UA targets ovarian cancer stem cells, inhibiting their
self-renewal, migration and stemness via suppression of the
PI3K/AKT and HIF-1α/ABCG2 pathways, and downregulation of CD133,
ALDH1, N-cadherin and vimentin. These mechanisms collectively
highlight UA's therapeutic potential in overcoming chemoresistance
and improving ovarian cancer treatment outcomes. UA, ursolic
acid.

Figure 2

Antitumor mechanisms of UA in
cervical and endometrial cancers. In cervical cancer, UA induces
apoptosis via Fas/caspase signaling, downregulates HPV E6/E7,
promotes autophagy through Atg5, triggers ER stress-mediated
apoptosis, and enhances cisplatin/paclitaxel sensitivity by
inhibiting NF-κB. In endometrial cancer, UA suppresses Cyclin D1
via MAPK and SCF complex inhibition, induces mitochondrial
apoptosis through caspase activation and Bcl-2/Bax modulation, and
inhibits PI3K-Akt and MAPK pathways to block proliferation and
promote cell death. UA, ursolic acid.

Figure 3

Antitumor mechanisms of UA in breast
cancer. UA inhibits proliferation and induces apoptosis in breast
cancer cells via pathways such as Keap1/Nrf2, Akt/mTOR, FoxM1 and
mitochondrial caspase signaling. It induces autophagy and metabolic
disruption through modulation of MAPK, SP1/CAV1, AMPK and AKT
pathways, and regulates glycolysis and mitochondrial function. UA
also targets breast cancer stem cells by suppressing Wnt/β-catenin,
AGO2/miR-9/miR-221 and NRF2 signaling, impairing stemness and
promoting ferroptosis. Additionally, UA inhibits invasion and
metastasis by downregulating MMP-2, u-PA, and PI3K/Akt, while
enhancing autophagy, apoptosis, and anti-inflammatory responses.
UA, ursolic acid.
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Copy and paste a formatted citation
Spandidos Publications style
Chen T, Sun S, Zhou Z and Zhang X: Ursolic acid: A natural pentacyclic triterpenoid with clinical promise in gynecological and breast cancers (Review). Oncol Rep 54: 153, 2025.
APA
Chen, T., Sun, S., Zhou, Z., & Zhang, X. (2025). Ursolic acid: A natural pentacyclic triterpenoid with clinical promise in gynecological and breast cancers (Review). Oncology Reports, 54, 153. https://doi.org/10.3892/or.2025.8986
MLA
Chen, T., Sun, S., Zhou, Z., Zhang, X."Ursolic acid: A natural pentacyclic triterpenoid with clinical promise in gynecological and breast cancers (Review)". Oncology Reports 54.5 (2025): 153.
Chicago
Chen, T., Sun, S., Zhou, Z., Zhang, X."Ursolic acid: A natural pentacyclic triterpenoid with clinical promise in gynecological and breast cancers (Review)". Oncology Reports 54, no. 5 (2025): 153. https://doi.org/10.3892/or.2025.8986
Copy and paste a formatted citation
x
Spandidos Publications style
Chen T, Sun S, Zhou Z and Zhang X: Ursolic acid: A natural pentacyclic triterpenoid with clinical promise in gynecological and breast cancers (Review). Oncol Rep 54: 153, 2025.
APA
Chen, T., Sun, S., Zhou, Z., & Zhang, X. (2025). Ursolic acid: A natural pentacyclic triterpenoid with clinical promise in gynecological and breast cancers (Review). Oncology Reports, 54, 153. https://doi.org/10.3892/or.2025.8986
MLA
Chen, T., Sun, S., Zhou, Z., Zhang, X."Ursolic acid: A natural pentacyclic triterpenoid with clinical promise in gynecological and breast cancers (Review)". Oncology Reports 54.5 (2025): 153.
Chicago
Chen, T., Sun, S., Zhou, Z., Zhang, X."Ursolic acid: A natural pentacyclic triterpenoid with clinical promise in gynecological and breast cancers (Review)". Oncology Reports 54, no. 5 (2025): 153. https://doi.org/10.3892/or.2025.8986
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