Ursolic acid: a pentacyclic triterpenoid that exhibits anticancer therapeutic potential by modulating multiple oncogenic targets

Sandhu, Sardul Singh; Rouz, Sharareh Khorami; Kumar, Suneel; Swamy, Nitin; Deshmukh, L. S.; Hussain, Arif; Haque, Shafiul; Tuli, Hardeep Singh

doi:10.1080/02648725.2022.2162257

Cited by 5 publications

(2 citation statements)

References 140 publications

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“…Since BCSCs exhibit resistance to traditional chemotherapy drugs such as PTX, there is an urgent need to develop novel drugs targeting BCSCs. UA has gained attention as a potent anticancer agent in various cancers through inducing apoptosis or ferroptosis ( 27 , 31 ). However, whether UA could target CSCs by overcoming ferroptosis resistance remains unclear.…”

Section: Resultsmentioning

confidence: 99%

Ursolic acid inhibits the proliferation of triple‑negative breast cancer stem‑like cells through NRF2‑mediated ferroptosis

Yang,

Liang,

Zhang

et al. 2024

Oncol Rep

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Ursolic acid (UA), a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices and medicinal plants, has various biological effects such as reducing inflammation, protecting cells from damage, and preserving brain function. However, its impact on ferroptosis in cancer stem-like cells remains unexplored. The present study investigated the effect of UA on MDA-MB-231 and BT-549 cell-derived triple-negative breast CSCs (BCSCs) and its potential ferroptosis pathway. The effects of ferroptosis on BCSCs were demonstrated by the detection of ferroptosis-related indexes including the intracellular level of glutathione, malondialdehyde, reactive oxygen species and iron. The effects of UA on the biological behaviors of BCSCs were analyzed by Cell Counting Kit-8, stemness indexes detection and mammosphere formation assay. The mechanism of UA induction on BCSCs was explored by reverse transcription-quantitative PCR and western blotting. BALB/c-nude mice were subcutaneously injected with MDA-MB-231-derived BCSCs to establish xenograft models to detect the effects of UA in vivo . The results revealed that BCSCs have abnormal iron metabolism and are less susceptible to ferroptosis. UA effectively reduces the stemness traits and proliferation of BCSCs in spheroids and mice models by promoting ferroptosis. It was observed that UA stabilizes Kelch-like ECH-associated protein 1 and suppresses nuclear factor erythroid-related factor 2 (NRF2) activation. These findings suggested that the ability of UA to trigger ferroptosis through the inhibition of the NRF2 pathway could be a promising approach for treating BCSCs, potentially addressing metastasis and drug resistance in triple-negative breast cancer (TNBC). This expands the clinical applications of UA and provides a theoretical basis for its use in TNBC treatment.

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Section: Resultsmentioning

confidence: 99%

Ursolic acid inhibits the proliferation of triple‑negative breast cancer stem‑like cells through NRF2‑mediated ferroptosis

Yang,

Liang,

Zhang

et al. 2024

Oncol Rep

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“…Ursolic acid exhibited antidiabetic, hepatoprotective, cardioprotective, antioxidant, anti-inflammatory and anticancer properties. [11][12][13] Moreover, due to its low bioavailability, nowadays ursolic acid-loaded chitosan nanoparticles (UACNP) are synthesized to enhance their therapeutic properties. Studies on ursolic acid nanoparticles against experimental carcinogenesis have not been documented well.…”

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confidence: 99%

Ursolic Acid-Loaded Chitosan Nanoparticles Modulate the Expression Pattern of Apoptotic Markers Towards Oral Tumour Inhibition in Golden Syrian Hamsters

2023

TJNPR

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Oral cancer is an aggressive life-threatening cancer that causes a severe health burden and high mortality around the globe. Oral cancer affects approximately 0.4 million people every year globally. Tobacco and alcohol abuse are pointed out as potent oral carcinoma risk factors. 1 Oral carcinoma frequently arises on lips, gums, tongue, palates and salivary glands. The treatment of oral carcinoma still faces significant difficulties because of its rapid progression, resistance to drugs, and lack of response, despite advancements in oral cancer treatments such as targeted therapy, gene therapy, and therapy with potent chemotherapeutic drugs. Early detection, prevention and early treatment can significantly improve oral cancer patients' life quality. 2,3 Cells with potentially harmful mutations are eliminated by apoptosis, an ordered and coordinated sequential process. Cancer cells avoid apoptosis by interfering with the actions of pro-apoptotic and antiapoptotic proteins. A defect in the apoptotic mechanism would result in uncontrollable and abnormal growth of cells that ultimately leads to the formation of a tumor. Cellular apoptosis has been aberrantly dysregulated at various stages of oral squamous cell carcinoma. 4,5

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Development of natural product-based targeted protein degraders as anticancer agents

Chen,

Feng,

Zhou

et al. 2024

Bioorganic Chemistry

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Ursolic acid: a pentacyclic triterpenoid that exhibits anticancer therapeutic potential by modulating multiple oncogenic targets

Cited by 5 publications

References 140 publications

Ursolic acid inhibits the proliferation of triple‑negative breast cancer stem‑like cells through NRF2‑mediated ferroptosis

Ursolic acid inhibits the proliferation of triple‑negative breast cancer stem‑like cells through NRF2‑mediated ferroptosis

Ursolic Acid-Loaded Chitosan Nanoparticles Modulate the Expression Pattern of Apoptotic Markers Towards Oral Tumour Inhibition in Golden Syrian Hamsters

Development of natural product-based targeted protein degraders as anticancer agents

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