A novel synthetic ursolic acid derivative inhibits growth and induces apoptosis in breast cancer cell lines

Li, Wei; Zhang, Hongxiu; Nie, Mingxiu; Wang, Wei; Liu, Zongtao; Chen, Ceshi; Chen, Haijun; Liu, Rong; Baloch, Zulqarnain; Ma, Ke

doi:10.3892/ol.2017.7578

Cited by 6 publications

(8 citation statements)

References 42 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Li and colleagues [ 88 ] synthesized novel ursolic acid derivative 42 ( Figure 4 , Table 2 ) with a nitrogen-containing heterocyclic scaffold and the privileged fragment at the C-28 position by treating UA with acetic anhydride (Ac 2 O) in dry pyridine under the 4-dimethylaminopyridine (CH 3 ) 2 NC 5 H 4 N) at room temperature for 2 h. The 3-acetylated UA was treated with oxalyl chloride at room temperature for 3 h to produce an intermediary 28-acyl chloride. This compound was then mixed at room temperature for 2 h to synthesize compound 42 .…”

Section: Pyrazolementioning

confidence: 99%

“…The results indicated that 42 significantly increased the number of SUM149PT and HCC1937 cells lines in the G 0 /G 1 phase in a dose-dependent manner. Compound 42 significantly induced apoptosis in breast cancer more than UA [ 88 ]. Chen et al [ 89 ] also synthesized 42 , which exhibited a remarkable growth of the inhibitory effect against HL-60 cells leukemia cells with an IC 50 value of 0.91 µM, approximately 100-fold more potent than UA [ 89 ].…”

Section: Pyrazolementioning

confidence: 99%

“…The study of the mechanism and the in vivo antitumor study of this compound demonstrated reduced apoptosis regulator (Bcl-2/Bax) ratio, disrupted mitochondrial potential and induced apoptosis, and suppressed the growth of Hela xenografts in nude mice [ 103 ]. Li et al [ 88 ] indicated that apoptosis in breast cancer cells was induced by ursolic acid piperazine hybrid derivative (compound 67 ( Figure 6 )), along with cell cycle arrest induction at S and G0/G1 phase. Thus, compound 67 is a promising therapeutic agent for the treatment of breast cancer.…”

Section: Piperazinementioning

confidence: 99%

See 2 more Smart Citations

Pentacyclic Triterpenoids with Nitrogen-Containing Heterocyclic Moiety, Privileged Hybrids in Anticancer Drug Discovery

et al. 2021

View full text Add to dashboard Cite

Pentacyclic triterpenoids are well-known phytochemicals with various biological activities commonly found in plants as secondary metabolites. The wide range of biological activities exhibited by triterpenoids has made them the most valuable sources of pharmacological agents. A number of novel triterpenoid derivatives with many skeletal modifications have been developed. The most important modifications are the formation of analogues or derivatives with nitrogen-containing heterocyclic scaffolds. The derivatives with nitrogen-containing heterocyclic compounds are among the most promising candidate for the development of novel therapeutic drugs. About 75% of FDA-approved drugs are nitrogen-containing heterocyclic moieties. The unique properties of heterocyclic compounds have encouraged many researchers to develop new triterpenoid analogous with pharmacological activities. In this review, we discuss recent advances of nitrogen-containing heterocyclic triterpenoids as potential therapeutic agents. This comprehensive review will assist medicinal chemists to understand new strategies that can result in the development of compounds with potential therapeutic efficacy.

show abstract

Section: Pyrazolementioning

confidence: 99%

Section: Pyrazolementioning

confidence: 99%

Section: Piperazinementioning

confidence: 99%

See 1 more Smart Citation

Pentacyclic Triterpenoids with Nitrogen-Containing Heterocyclic Moiety, Privileged Hybrids in Anticancer Drug Discovery

et al. 2021

View full text Add to dashboard Cite

show abstract

“…To enhance the bioavailability and anticancer activities, UA was chemically modified by Li et al Using a nitrogenous heterocyclic scaffold and a privileged fragment at C-28, they synthesized a new derivative FZU3010. The results of Sulforhodimine B assay and flow cytometry showed that FZU3010 inhibited proliferation and induced apoptosis in SUM149PT and HCC1937 cell lines [ 50 ].…”

Section: Introductionmentioning

confidence: 99%

“…It was also observed that UA inhibited inflammation in BC cells by down-regulating NF-κB, thus halting further progression [ 37 ]. A synthetic derivative of UA, FZU3010 caused cell cycle arrest in BC cells at S and G0/G1 phase leading to programmed cell death [ 50 ].…”

Section: Introductionmentioning

confidence: 99%

Ursolic acid: a natural modulator of signaling networks in different cancers

et al. 2022

View full text Add to dashboard Cite

Incidence rate of cancer is estimated to increase by 40% in 2030. Furthermore, the development of resistance against currently available treatment strategies has contributed to the cancer-associated mortality. Scientists are now looking for the solutions that could help prevent the disease occurrence and could provide a pain-free treatment alternative for cancers. Therefore, efforts are now put to find a potent natural compound that could sever this purpose. Ursolic acid (UA), a triterpene acid, has potential to inhibit the tumor progression and induce sensitization to conventional treatment drugs has been documented. Though, UA is a hydrophobic compound therefore it is usually chemically modified to increase its bioavailability prior to administration. However, a thorough literature indicating its mechanism of action and limitations for its use at clinical level was not reviewed. Therefore, the current study was designed to highlight the potential mechanism of UA, its anti-cancer properties, and potential applications as therapeutic compound. This endeavour is a valuable contribution in understanding the hurdles preventing the translation of its potential at clinical level and provides foundations to design new studies that could help enhance its bioavailability and anti-cancer potential for various cancers.

show abstract

Inhibitory Effect and Mechanism of Ursolic Acid on Cisplatin‐Induced Resistance and Stemness in Human Lung Cancer A549 Cells

Fan

Wang²,

Chen

et al. 2023

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

The survival rate of lung cancer patients remains low largely due to chemotherapy resistance during treatment, and cancer stem cells (CSCs) may hold the key to targeting this resistance. Cisplatin is a chemotherapy drug commonly used in cancer treatment, yet the mechanisms of intrinsic cisplatin resistance have not yet been determined because lung CSCs are hard to identify. In this paper, we proposed a mechanism relating to the function of ursolic acid (UA), a new drug, in reversing the cisplatin resistance of lung cancer cells regulated by CSCs. Human lung cancer cell line A549 was selected as the model cell and treated to become a cisplatin-resistant lung cancer cell line (A549-CisR), which was less sensitive to cisplatin and showed an enhanced capability of tumor sphere formation. Furthermore, in the A549-CisR cell line expression, levels of pluripotent stem cell transcription factors Oct-4, Sox-2, and c-Myc were increased, and activation of the Jak2/Stat3 signaling pathway was promoted. When UA was applied to the cisplatin-resistant cells, levels of the pluripotent stem cell transcription factors were restrained by the inhibition of the Jak2/Stat3 signaling pathway, which reduced the enrichment of tumor stem cells, and in turn, reversed cisplatin resistance in lung cancer cells. Hence, as a potential antitumor drug, UA may be able to inhibit the enrichment of the lung CSC population by inhibiting the activation of the Jak2-Stat3 pathway and preventing the resistance of lung cancer cells to cisplatin.

show abstract

A novel synthetic ursolic acid derivative inhibits growth and induces apoptosis in breast cancer cell lines

Cited by 6 publications

References 42 publications

Pentacyclic Triterpenoids with Nitrogen-Containing Heterocyclic Moiety, Privileged Hybrids in Anticancer Drug Discovery

Pentacyclic Triterpenoids with Nitrogen-Containing Heterocyclic Moiety, Privileged Hybrids in Anticancer Drug Discovery

Ursolic acid: a natural modulator of signaling networks in different cancers

Inhibitory Effect and Mechanism of Ursolic Acid on Cisplatin‐Induced Resistance and Stemness in Human Lung Cancer A549 Cells

Contact Info

Product

Resources

About