Ursolic acid: An overview on its cytotoxic activities against breast and colorectal cancer cells

Chan, Eric Wei Chiang; Soon, Chu Yong; Tan, Joash Ban Lee; Wong, Siu Kuin; Hui, Yew Woh

doi:10.1016/j.joim.2019.03.003

Cited by 54 publications

(40 citation statements)

References 71 publications

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“…e increasing concentration of ursolic acid and thujone induced cell death through the necrosis process which, detected with characteristic morphological changes of necrosis in U937 and HL-60 cells such as membrane bubbling, detached from neighbor cells and evaginations [28]. Similarly, morphological changes were reported in the ursolic acid-treated various cancer cells that support the present findings [18][19][20][33][34][35][36].…”

Section: Antiproliferative Activitysupporting

confidence: 87%

“…Ursolic acid is reported to have antiproliferative activity on different types of cancers such as lung, colon, breast, renal, prostate, melanoma, and leukemia [18][19][20][33][34][35][36]. Many reports support the antiproliferative potential of ursolic acid because it might induce the apoptosis process in different mode on various types of cell lines [37,38].…”

Section: Antiproliferative Activitymentioning

confidence: 99%

“…It mainly induced apoptosis in HL-60 leukemia cells accompanied by mediating the release of intracellular calcium ions [39], inhibiting DNA synthesis [40] and blocking the cell cycle process [39,41], and inducing Atg5-dependent autophagy [42] and mitochondria dependent apoptosis [19] which supports the findings of the present study. Moreover, many reviews described the mode of action of ursolic acid in the control of cancer cells [18][19][20][21].…”

Section: Antiproliferative Activitymentioning

confidence: 99%

“…However, there is no data available on the antioxidant and antiproliferative properties of the isolated compound thujone (from Elaeagnus indica). Even though anticancer and antiproliferative activity of ursolic acid (isolated from Memecylon edule) were reported [18][19][20][21], there is no data available on growth inhibitory effect of ursolic acid on the human leukemic monocyte lymphoma (U-937) cells, and antioxidant potential of ursolic acid was the least explored. Moreover, there are no previous studies available on the in silico inhibition interactions of thujone and ursolic acid with topoisomerase II in detail.…”

Section: Introductionmentioning

confidence: 99%

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Antioxidant and Antiproliferative Potential of Bioactive Molecules Ursolic Acid and Thujone Isolated from Memecylon edule and Elaeagnus indica and Their Inhibitory Effect on Topoisomerase II by Molecular Docking Approach

Ramalingam

Arumugam²,

Lee

et al. 2020

BioMed Research International

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The present study aimed to evaluate the antioxidant and antiproliferative potential of ursolic acid and thujone isolated from leaves of Elaeagnus indica and Memecylon edule and their inhibitory effect on topoisomerase II using molecular docking study. The isolated ursolic acid and thujone were examined for different types of free radicals scavenging activity, the antiproliferative potential on U-937 and HT-60 cell lines by adopting standard methods. Further, these compounds were docked with the active site of the ATPase region of topoisomerase II. The findings of the research revealed that ursolic acid harbor strong antioxidant and antiproliferative capacity with low IC50 values than the thujone in all tested methods. Moreover, ursolic acid shows significant inhibition effect on topoisomerase II with a considerable docking score (−8.0312) and GLIDE energy (−51.86 kca/mol). The present outcome concludes that ursolic acid possesses significant antioxidant and antiproliferative potential, which can be used in the development of novel antioxidant and antiproliferative agents in the future.

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Section: Antiproliferative Activitysupporting

confidence: 87%

Section: Antiproliferative Activitymentioning

confidence: 99%

Section: Antiproliferative Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antioxidant and Antiproliferative Potential of Bioactive Molecules Ursolic Acid and Thujone Isolated from Memecylon edule and Elaeagnus indica and Their Inhibitory Effect on Topoisomerase II by Molecular Docking Approach

Ramalingam

Arumugam²,

Lee

et al. 2020

BioMed Research International

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“…Studies also suggest that a proper life-style maintenance including the controlled diet could reduce the abnormal poly formation and further cancer. Ursolic acid is a phytochemical present in most plants and has the ability to reduce the cell proliferation of breast and colon cancer cells through various pathways [2].…”

Section: Introductionmentioning

confidence: 99%

Phospholipase A2 Isoforms in Benzo (α) Pyrene-Induced Molecular Changes in Colon Cancer Cells: A Plausible Therapeutic Target

Sharma¹,

Yadav²,

Sharma³

et al. 2020

Preprint

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Background: Colorectal cancer (CRC) is the third most common cancer prevalent in men, and the second in women worldwide. The exact cause and pathogenesis of this disease remains unknown. In every cell multiple phospholipase A2 (PLA2) exists, but their contribution to the cell function has yet not been determined. The increased activity of these isoforms may be important in the generation of inflammatory mediators which finally are involved in the initiation of carcinogenesis. This study has explored the pathways involved in the differential response of HCT-15 and HT-29 colon cell lines during benzo(α)pyrene [B(α)P]-induced molecular changes.Methods: HT-29 and HCT-15 cells were used for the present study. Benzo(α)pyrene [B(α)P]-induced molecular changes were evaluated through cell viability using MTT assay, reactive oxygen species (ROS) measurement using 2,7 dichloro-dihydro-fluorescin diacetate (DCFH-DA), The gene expressions of PLA2 isoforms were estimated by RT- PCR. Further, knockdown of PLA2 isoform in transfected cells was done with siRNA.Results: The cell viability decreased significantly after exposure with B(α)P in both cell lines. Reactive oxygen species (ROS) production after exposure with B(α)P was significantly induced in both types of colon cell lines. The gene expressions of PLA2 isoforms were also estimated. Three PLA2 isoforms such as IB and, IID, IVA were induced after exposure with B(α)P respectively in HT -29 and HCT-15 cell lines. Further, a significant knockdown of PLA2 isoform in transfected cells with siRNA, and B(α)P exposure was observed in HCT-15 and HT-29 cells. There was a significant induction of ROS in IVA transfected HCT-15 cells exposure with B(α)P.Conclusion: It is concluded that each cell line behaved differently, specific PLA2 siRNA are involved in controlling the cascades related ROS, depending upon the origin of the cells. Secretary phospholipase A2 (sPLA2) inhibitors are likely to have a therapeutic potential in colon pathologies.

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PXR–ABC drug transporters/CYP‐mediated ursolic acid transport and metabolism in vitro and vivo

Wen

Zhou

2020

Archiv der Pharmazie

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The transporting kinetics and metabolic kinetics of ursolic acid were studied in transgenic cell models. Then, the pharmacokinetics features of ursolic acid and the expression of ATP‐binding cassette transporters (ABC transporter) and cytochrome P450 (CYP) enzymes in tissues after pregnane X receptor (PXR) activation by 5‐pregnen‐3β‐ol‐20‐one‐16α‐carbonitrile (PCN) were investigated in rats. After silencing of PXR in Caco2–siRNA–PXR cells, there was a decrease in the protein abundance of P‐glycoprotein, breast cancer‐resistant protein, multidrug resistance‐associated protein 2 (MRP2), and CYP2C9. The apparent permeability (PDR) values of 10, 20, and 50 µM ursolic acid in Caco2 cells were 2.19 ± 0.44, 1.40 ± 0.17, and 1.25 ± 0.07, respectively, whereas in Caco2–siRNA–PXR cells, they were 1.85 ± 0.36, 1.24 ± 0.11, and 1.19 ± 0.04, respectively. PXR–RXRα would significantly activate ABC transporter expression in Caco2 cells. Compared with Caco2 cells, when the concentrations of ursolic acid were 10, 20, and 50 µM, the PDR values increased in Caco2–PXR–RXRα cells after PXR activation: 1.60 ± 0.31 versus 1.97 ± 0.21, 1.46 ± 0.08 versus 2.01 ± 0.19, and 1.32 ± 0.26 versus 2.09 ± 0.22, respectively. Simultaneously, PXR–RXRα would activate the expression of CYP2C9; metabolic kinetics of ursolic acid in CYP metabolizing enzyme lysate of Caco2 cells and Caco2–PXR–RXR cells was studied and it was found that the Km values were 81.99 ± 44.32 and 60.05 ± 29.62 µg/ml, and Vmax values were 3.77 ± 0.86 and 3.41 ± 0.96 µg · ml−1 · min−1, respectively. However, in human CYP metabolizing recombinase, we found that both CYP2C9 and CYP34A were involved in the metabolism of ursolic acid. Vm and Km values for CYP3A4 and CYP2C9 were 3.57 ± 1.12 µg · ml−1 · min−1 and 81.71 ± 18.38 µg/ml, 3.85 ± 1.46 µg · ml−1 · min−1 and 62.18 ± 14.56 µg/ml, respectively. As a strong agonist for mouse pxr, PCN could significantly affect pharmacokinetics of ursolic acid in rats, and it showed discrepant effects on messenger RNA expression of cyp and transporters in tissues.

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Ursolic acid: An overview on its cytotoxic activities against breast and colorectal cancer cells

Cited by 54 publications

References 71 publications

Antioxidant and Antiproliferative Potential of Bioactive Molecules Ursolic Acid and Thujone Isolated from Memecylon edule and Elaeagnus indica and Their Inhibitory Effect on Topoisomerase II by Molecular Docking Approach

Antioxidant and Antiproliferative Potential of Bioactive Molecules Ursolic Acid and Thujone Isolated from Memecylon edule and Elaeagnus indica and Their Inhibitory Effect on Topoisomerase II by Molecular Docking Approach

Phospholipase A2 Isoforms in Benzo (α) Pyrene-Induced Molecular Changes in Colon Cancer Cells: A Plausible Therapeutic Target

PXR–ABC drug transporters/CYP‐mediated ursolic acid transport and metabolism in vitro and vivo

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