Inhibitory Effect of Ursolic Acid on the Migration and Invasion of Doxorubicin-Resistant Breast Cancer

Zong, Li; Cheng, Guorong; Zhao, Jinsong; Zhuang, Xiaoyu; Zheng, Zhong; Liu, Zhiqiang; Song, Fengrui

doi:10.3390/molecules27041282

Cited by 12 publications

(11 citation statements)

References 46 publications

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“…This study also provides a possible explanation for the beneficial effects of UA on multidrug resistance. Several studies have reported that UA re-sensitizes drug-resistant cancer cells towards chemotherapy [ 14 , 70 , 71 ]. One of the mechanisms by which drug-resistant cancer cells can evade cell death is by storing basic drugs in lysosomes, thus hindering them from reaching their sites of action [ 72 , 73 , 74 ].…”

Section: Discussionmentioning

confidence: 99%

Ursolic Acid Impairs Cellular Lipid Homeostasis and Lysosomal Membrane Integrity in Breast Carcinoma Cells

Fogde

Xavier

Balnytė

et al. 2022

Cells

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Cancer is one of the leading causes of death worldwide, thus the search for new cancer therapies is of utmost importance. Ursolic acid is a naturally occurring pentacyclic triterpene with a wide range of pharmacological activities including anti-inflammatory and anti-neoplastic effects. The latter has been assigned to its ability to promote apoptosis and inhibit cancer cell proliferation by poorly defined mechanisms. In this report, we identify lysosomes as the essential targets of the anti-cancer activity of ursolic acid. The treatment of MCF7 breast cancer cells with ursolic acid elevates lysosomal pH, alters the cellular lipid profile, and causes lysosomal membrane permeabilization and leakage of lysosomal enzymes into the cytosol. Lysosomal membrane permeabilization precedes the essential hallmarks of apoptosis placing it as an initial event in the cascade of effects induced by ursolic acid. The disruption of the lysosomal function impairs the autophagic pathway and likely partakes in the mechanism by which ursolic acid kills cancer cells. Furthermore, we find that combining treatment with ursolic acid and cationic amphiphilic drugs can significantly enhance the degree of lysosomal membrane permeabilization and cell death in breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Ursolic Acid Impairs Cellular Lipid Homeostasis and Lysosomal Membrane Integrity in Breast Carcinoma Cells

Fogde

Xavier

Balnytė

et al. 2022

Cells

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“…UA has been reported to inhibit the migration and invasion of drug-resistant breast cancer cells . To evaluate the inhibitory effects of UA and (UA)-PLGA/CS NPs on cell migration and invasion in breast cancer cells, the same concentration of UA was used and analyzed in MDA-MB-231 cells, which are characterized by their highly aggressive, metastatic, and invasive nature.…”

Section: Resultsmentioning

confidence: 99%

Chitosan-Coated Poly(lactic-co-glycolic acid) Nanoparticles Loaded with Ursolic Acid for Breast Cancer Therapy

Payomhom,

Panyain,

Sakonsinsiri

et al. 2024

ACS Appl. Nano Mater.

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Ursolic acid (UA), a pentacyclic triterpenoid found in various fruits and herbs, has the potential as an anticancer agent against multiple cancer types. Nevertheless, its clinical use was limited by its poor water solubility. To overcome this drawback, several nanocarriers were proposed to increase the bioavailability and efficacy of UA. However, the insights into the cellular targets and mechanisms of UA and UA nanoparticles (NPs) remain limited. In this study, chitosan-coated poly(lactic-co-glycolic acid) (PLGA/CS) NPs were loaded with UA. The obtained (UA)-PLGA/CS NPs were spherical with an approximate size of 250 nm and an encapsulation efficiency of 25%. Owing to their promising potential as drug carriers, the NPs were successfully delivered into breast cancer cells (MCF-7 and MDA-MB-231). Moreover, (UA)-PLGA/CS NPs enhanced the anticancer activity of UA, as evidenced by the IC 50 values of 26.74 and 40.67 μM in MCF-7 and MDA-MB-231 cells, respectively. These values were lower than those of free UA (90.25 and 85.63 μM in MCF-7 and MDA-MB-231 cells, respectively). The improved cytotoxicity induced by (UA)-PLGA/CS NPs can be attributed to apoptosis induction, collective cell migration and invasion inhibition, and cell proliferation pathway disruption. These findings led to a better understanding of the anticancer effects and molecular mechanisms of (UA)-PLGA/CS NPs and their potential targets for breast cancer therapy.

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“…Phytochemicals including UA may exert powerful efficacy against a variety of malignancies, such as CRC, gastric cancer, breast cancer, prostate cancer, , and lung cancer, with fewer adverse reactions in comparison with the compounds of chemotherapy, which gives rise to broad utilization of phytochemicals as nutraceuticals for intervention in various cancers. However, the action mechanisms for most phytochemicals remain to be clarified, and UA is one of them in great need of exploration.…”

Section: Discussionmentioning

confidence: 99%

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/β-Catenin Signaling Pathway Activity

Zhao

Tang

Qiu

et al. 2023

J. Agric. Food Chem.

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Overwhelming evidence points to an abnormally active Wnt/β-catenin signaling as a key player in colorectal cancer (CRC) pathogenesis. Ursolic acid (UA) is a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices, and medicinal plants. UA has been shown to have potent bioactivity against a variety of cancers, including CRC, with the action mechanism obscure. Our study tried to learn more about the efficacy of UA on CRC and its functional mechanism amid the Wnt/β-catenin signaling cascade. We determined the efficacy of UA on CRC SW620 cells with respect to the proliferation, migration, clonality, apoptosis, cell cycle, and Wnt/β-catenin signaling cascade, with assessment of the effect of UA on normal colonic NCM460 cells. Also, the effects of UA on the tumor development, apoptosis, cell cycle, and Wnt/β-catenin signaling axis were evaluated after a subcutaneous SW620 xenograft tumor model was established in mice. In this work, we showed that UA drastically suppressed proliferation, migration, and clonality; induced apoptosis; and arrested the cell cycle at the G0/G1 phase of SW620 cells, without the influence on NCM460 cells, accompanied by weakened activity of the Wnt/β-catenin signaling pathway. Besides, UA markedly deterred the growth of the xenograft tumor, ameliorated pathological features, triggered apoptosis, and arrested the cell cycle in xenograft CRC tissue, by lessening the Wnt/β-catenin signaling cascade. Overall, UA may inhibit the malignant phenotype, induce apoptosis, and arrest the cell cycle of CRC, potentially by attenuating the Wnt/β-catenin signaling axis, providing insights into the mechanism for the potency of UA on CRC.

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Inhibitory Effect of Ursolic Acid on the Migration and Invasion of Doxorubicin-Resistant Breast Cancer

Cited by 12 publications

References 46 publications

Ursolic Acid Impairs Cellular Lipid Homeostasis and Lysosomal Membrane Integrity in Breast Carcinoma Cells

Ursolic Acid Impairs Cellular Lipid Homeostasis and Lysosomal Membrane Integrity in Breast Carcinoma Cells

Chitosan-Coated Poly(lactic-co-glycolic acid) Nanoparticles Loaded with Ursolic Acid for Breast Cancer Therapy

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/β-Catenin Signaling Pathway Activity

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