Ursolic acid augments the chemosensitivity of drug-resistant breast cancer cells to doxorubicin by AMPK-mediated mitochondrial dysfunction

Luo, Fazhen; Zhao, Jianhua; Liu, Shuo; Xue, Yuanfei; Tang, Dongyun; Yang, Jing; Ye, Mei; Li, Guowen; Xie, Yan

doi:10.1016/j.bcp.2022.115278

Cited by 16 publications

(9 citation statements)

References 58 publications

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“…Several studies have shown that UA inhibited cancer cell proliferation and reduced cell viability by inducing apoptosis in various cancer cell lines, including breast cancer cells. , Kim et al, 2011, reported that UA inhibited breast cancer cell proliferation by inducing apoptosis through the mitochondria-mediated pathway . In line with the study conducted by Luo et al, 2022, UA inhibited the growth of drug-resistant breast cancer cells via increased p -AMPK levels, resulting in mitochondrial dysfunction, cell cycle arrest, and ROS production . Because (UA)-PLGA/CS NPs displayed a stronger cytotoxicity against breast cancer cells than free UA, further analysis of cell death induction was performed.…”

Section: Resultsmentioning

confidence: 77%

“…58 In line with the study conducted by Luo et al, 2022, UA inhibited the growth of drug-resistant breast cancer cells via increased p-AMPK levels, resulting in mitochondrial dysfunction, cell cycle arrest, and ROS production. 59 Because (UA)-PLGA/CS NPs displayed a stronger cytotoxicity against breast cancer cells than free UA, further analysis of cell death induction was performed. The IC 50 value of (UA)-PLGA/CS NPs was used to investigate the mode of cell death.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 77%

Section: ■ Results and Discussionmentioning

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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“…Another advantage of resveratrol is the reduction in liver injury caused by doxorubicin-induced oxidative stress through the AMPK/Nrf2 pathway [ 256 ]. Ursolic acid (UA) was reported in a recent study to activate AMPK phosphorylation and in turn inhibit mTOR and PGC-1α, finally impairing mitochondrial functions, which is beneficial to doxorubicin resistance cells [ 257 ]. Agents belonging to the statin family are also activators of AMPK and they exhibit potential anti-cancer effects by interfering with the mevalonate signaling pathway.…”

Section: Potential Ampk Modulators Of Natural Products From Herbal Me...mentioning

confidence: 99%

Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer

et al. 2023

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Breast cancer is a common cancer in women worldwide. The existing clinical treatment strategies have been able to limit the progression of breast cancer and cancer metastasis, but abnormal metabolism, immunosuppression, and multidrug resistance involving multiple regulators remain the major challenges for the treatment of breast cancer. Adenosine 5′-monophosphate (AMP)-Activated Protein Kinase (AMPK) can regulate metabolic reprogramming and reverse the “Warburg effect” via multiple metabolic signaling pathways in breast cancer. Previous studies suggest that the activation of AMPK suppresses the growth and metastasis of breast cancer cells, as well as stimulating the responses of immune cells. However, some other reports claim that the development and poor prognosis of breast cancer are related to the overexpression and aberrant activation of AMPK. Thus, the role of AMPK in the progression of breast cancer is still controversial. In this review, we summarize the current understanding of AMPK, particularly the comprehensive bidirectional functions of AMPK in cancer progression; discuss the pharmacological activators of AMPK and some specific molecules, including the natural products (including berberine, curcumin, (−)-epigallocatechin-3-gallate, ginsenosides, and paclitaxel) that influence the efficacy of these activators in cancer therapy; and elaborate the role of AMPK as a potential therapeutic target for the treatment of breast cancer.

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“… The potential mechanism underlying the anticancer effects of ursolic acid ( 64–68 ). UA upregulates and activates the expression of the cell tumor antigen p53 and the AMP-activated protein kinase (AMPK) signaling pathway, respectively, together with suppression of the mammalian target of rapamycin (mTOR) pathways and downregulation of the apoptosis regulator Bcl-2.…”

Section: Beneficial Effects Of Uamentioning

confidence: 99%

Ursolic acid: biological functions and application in animal husbandry

Liu,

Qin,

Cheng

et al. 2023

Front. Vet. Sci.

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Ursolic acid (UA) is a plant-derived pentacyclic triterpenoid with 30 carbon atoms. UA has anti-inflammatory, antioxidative, antimicrobial, hepato-protective, anticancer, and other biological activities. Most studies on the biological functions of UA have been performed in mammalian cell (in vitro) and rodent (in vivo) models. UA is used in animal husbandry as an anti-inflammatory and antiviral agent, as well as for enhancing the integrity of the intestinal barrier. Although UA has been shown to have significant in vitro bacteriostatic effects, it is rarely used in animal nutrition. The use of UA as a substitute for oral antibiotics or as a novel feed additive in animal husbandry should be considered. This review summarizes the available data on the biological functions of UA and its applications in animal husbandry.

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Ursolic acid augments the chemosensitivity of drug-resistant breast cancer cells to doxorubicin by AMPK-mediated mitochondrial dysfunction

Cited by 16 publications

References 58 publications

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

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

Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer

Ursolic acid: biological functions and application in animal husbandry

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