Evidence of the Beneficial Effects of Ursolic Acid against Lung Cancer

Kornel, Amanda; Nadile, Matteo; Tsiani, Evangelia

doi:10.3390/molecules27217466

Cited by 7 publications

(4 citation statements)

References 95 publications

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“…Our study has shown that bearberry leaves are another source of compounds with proapoptotic activity against gliomas and that the Et extract has much higher anticancer activity than Aq (Figures 2 and 3). Additionally, ethanolic extracts contain UA and OA (Table 1), which are characterized by anticancer activity against different types of cancer [38,60,61]. Attention should also be paid to the chemical profile of Aq characterized by higher contents of HQ and COR in comparison with Et but, above all, to the negative correlation between HQ-Ap and COR-Ap in the two studied cell lines.…”

Section: Discussionmentioning

confidence: 99%

Phytochemical Profiles and Anti-Glioma Activity of Bearberry Arctostaphylos uva-ursi (L.) Spreng. Leaf Extracts

Sugier,

Jakubowicz-Gil,

Zając

et al. 2024

Applied Sciences

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The use of diversified raw materials and various extractant types is justified because the varied chemical composition of extracts obtained via extraction determines their biological activity. Therefore, the objective of this study was (i) to characterize the chemical profile of two types of bearberry extracts (70% ethanolic and water) and (ii) to investigate the biological activity of the analyzed extracts through an assessment of their possible proapoptotic effects on glioma cell lines. The HPLC-UV analysis of individual compounds was performed for the determination of the phytochemical profile of the bearberry extracts, and their total phenolic content (TPC) and total flavonoid content (TFC) were determined spectrophotometrically. The induction of apoptosis, autophagy, and necrosis in anaplastic astrocytoma MOGGCCM and human glioblastoma LN229 cell lines were investigated. The results indicated that the ethanolic (Et) and aqueous (Aq) extracts had different chemical profiles. The TPC in the Et was ca. 60% higher than in the Aq. Similarly, the TFC and methylarbutin (mARB) concentrations were significantly higher in the Et. On the other hand, the concentration of hydroquinone (HQ) was ca. 70% and that of corilagin (COR) was ca. 100% higher in the Aq. In turn, the presence of ursolic acid (UA) and oleanolic acid (OA) was confirmed solely in the Et. In contrast to Aq, Et demonstrated high proapoptotic activity. At the concentration of 2 µL/mL, the level of apoptosis varied between 14.7% and 26% in the case of the MOGGCCM cells and between 12.3% and 33.3% in the case of the LN229 cell line. The knowledge and information obtained in this study indicate a need for further research on the anticancer effect of the studied bearberry phytochemicals on the MOGGCCM and LN229 cell lines and for the elucidation of their molecular anticancer mechanisms.

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Section: Discussionmentioning

confidence: 99%

Phytochemical Profiles and Anti-Glioma Activity of Bearberry Arctostaphylos uva-ursi (L.) Spreng. Leaf Extracts

Sugier,

Jakubowicz-Gil,

Zając

et al. 2024

Applied Sciences

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“…These data together strongly suggested that the effects by UA treatment on AR expression and signaling is likely through its inhibition of RORγ function in the PCa cells. Several studies showed that UA can inhibit cancer cell and tumor growth by interfering with cell cycle, proliferation, apoptosis, inflammation, angiogenesis, and metastasis ( Iqbal et al, 2018 ; Kornel et al, 2022 ; Zafar et al, 2022 ). However, there has been no evidence showing that UA can affect AR expression and/or AR signaling, which is the key driver of PCa development and progression.…”

Section: Discussionmentioning

confidence: 99%

Natural compounds ursolic acid and digoxin exhibit inhibitory activities to cancer cells in RORγ-dependent and -independent manner

2023

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Natural compounds ursolic acid (UA) and digoxin isolated from fruits and other plants display potent anti-cancer effects in preclinical studies. UA and digoxin have been at clinical trials for treatment of different cancers including prostate cancer, pancreatic cancer and breast cancer. However, they displayed limited benefit to patients. Currently, a poor understanding of their direct targets and mechanisms of action (MOA) severely hinders their further development. We previously identified nuclear receptor RORγ as a novel therapeutic target for castration-resistant prostate cancer (CRPC) and triple-negative breast cancer (TNBC) and demonstrated that tumor cell RORγ directly activates gene programs such as androgen receptor (AR) signaling and cholesterol metabolism. Previous studies also demonstrated that UA and digoxin are potential RORγt antagonists in modulating the functions of immune cells such as Th17 cells. Here we showed that UA displays a strong activity in inhibition of RORγ-dependent transactivation function in cancer cells, while digoxin exhibits no effect at clinically relevant concentrations. In prostate cancer cells, UA downregulates RORγ-stimulated AR expression and AR signaling, whereas digoxin upregulates AR signaling pathway. In TNBC cells, UA but not digoxin alters RORγ-controlled gene programs of cell proliferation, apoptosis and cholesterol biosynthesis. Together, our study reveals for the first-time that UA, but not digoxin, acts as a natural antagonist of RORγ in the cancer cells. Our finding that RORγ is a direct target of UA in cancer cells will help select patients with tumors that likely respond to UA treatment.

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“…UA modulates different pharmacological pathways, leading to multifaceted health benefits and the prevention of chronic diseases [23,55,56]. In fact, UA demonstrated antiproliferative effects against hepatocellular carcinoma [57,58], lung cancer [59,60], leukemia [61][62][63], breast cancer [64,65], prostate and urogenital cancers [66,67], and cervical cancer [68,69].…”

Section: Peer Review 2 Of 19mentioning

confidence: 99%

Overview of Ursolic Acid Potential for the Treatment of Metabolic Disorders, Autoimmune Diseases, and Cancers via Nuclear Receptor Pathways

Kadasah,

Radwan

2023

Biomedicines

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Nuclear receptors (NRs) form a family of druggable transcription factors that are regulated by ligand binding to orchestrate multifaceted physiological functions, including reproduction, immunity, metabolism, and growth. NRs represent attractive and valid targets for the management and treatment of a vast array of ailments. Pentacyclic triterpenes (PTs) are ubiquitously distributed natural products in medicinal and aromatic plants, of which ursolic acid (UA) is an extensively studied member, due to its diverse bio-pertinent activities against different cancers, inflammation, aging, obesity, diabetes, dyslipidemia, and liver injury. In fact, PTs share a common lipophilic structure that resembles NRs’ endogenous ligands. Herein, we present a review of the literature on UA’s effect on NRs, showcasing the resulting health benefits and potential therapeutic outcomes. De facto, UA exhibited numerous pharmacodynamic effects on PPAR, LXR, FXR, and PXR, resulting in remarkable anti-inflammatory, anti-hyperlipidemic, and hepatoprotective properties, by lowering lipid accumulation in hepatocytes and mitigating non-alcoholic steatohepatitis (NASH) and its subsequent liver fibrosis. Furthermore, UA reversed valproate and rifampicin-induced hepatic lipid accumulation. Additionally, UA showed great promise for the treatment of autoimmune inflammatory diseases such as multiple sclerosis and autoimmune arthritis by antagonizing RORγ. UA exhibited antiproliferative effects against skin, prostate, and breast cancers, partially via PPARα and RORγ pathways. Herein, for the first time, we explore and provide insights into UA bioactivity with respect to NR modulation.

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Evidence of the Beneficial Effects of Ursolic Acid against Lung Cancer

Cited by 7 publications

References 95 publications

Phytochemical Profiles and Anti-Glioma Activity of Bearberry Arctostaphylos uva-ursi (L.) Spreng. Leaf Extracts

Phytochemical Profiles and Anti-Glioma Activity of Bearberry Arctostaphylos uva-ursi (L.) Spreng. Leaf Extracts

Natural compounds ursolic acid and digoxin exhibit inhibitory activities to cancer cells in RORγ-dependent and -independent manner

Overview of Ursolic Acid Potential for the Treatment of Metabolic Disorders, Autoimmune Diseases, and Cancers via Nuclear Receptor Pathways

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