Cytotoxicity of oleanolic and ursolic acid derivatives toward hepatocellular carcinoma and evaluation of NF-κB involvement

Fontana, Gianfranco; Bruno, Maurizio; Notarbartolo, Monica; Labbozzetta, Manuela; Poma, Paola; Spinella, Alberto; Rosselli, Sergio

doi:10.1016/j.bioorg.2019.103054

Cited by 35 publications

(18 citation statements)

References 30 publications

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“…The role of this transcriptional factor is well confirmed in numerous types of cancer [35], related to all phases of cancer develop as tumorigenesis, progression, invasion and metastasis, and its overexpression can cause the aberrant expression of the protein responsible of multidrug resistance [5,36]. For these reasons, NF-κB is often studied as a potential target for the treatment of malignant tumors [37,38,39], including AML [40] for which the therapeutic choice is restricted to few anti-blastic drugs towards which cancer cells develop early resistance. Most recently, new research is being conducted towards checkpoint inhibitors and cancer immunotherapy, like CAR T-cell therapy, but the side effects are multiple and sometimes characterized by unacceptable toxicity [41].…”

Section: Discussionmentioning

confidence: 99%

Antitumor Mechanism of the Essential Oils from Two Succulent Plants in Multidrug Resistance Leukemia Cell

et al. 2019

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Drug resistance remains a major challenge in the treatment of cancer. The multiplicity of the drug resistance determinants raises the question about the optimal strategies to deal with them. Essential oils showed to inhibit the growth of different tumor cell types. Essential oils contain several chemical classes of compounds whose heterogeneity of active moieties can help prevent the development of drug resistance. In the present paper, we analyzed, by gas chromatography-mass spectrometry the chemical composition of the essential oil of the leaves of Kalanchoe beharensis obtained by hydrodistillation and compared the chemical composition of its essential oil with that of Cyphostemma juttae. Our results demonstrated the anticancer and proapoptotic activities of both species against acute myeloid leukemia on an in vitro model and its multidrug resistant variant involving NF-κB pathway. The essential oils of both species produced a significant decrease in many targets of NF-κB both at mRNA and protein levels. The results corroborate the idea that essential oils may be a good alternative to traditional drugs in the treatment of cancer, especially in drug resistant cancer.

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Section: Discussionmentioning

confidence: 99%

Antitumor Mechanism of the Essential Oils from Two Succulent Plants in Multidrug Resistance Leukemia Cell

et al. 2019

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“…Also, biotransformation of ULA with the fungus Aspergillus flavus resulted in isolation of UNA [24]. Moreover, UNA can be synthesized via Jones oxidation, a technique that uses sulfuric acid, chromic trioxide, and acetone to oxidise alcohol [20,[25][26][27].…”

Section: Synthesis Of Ursonic Acidmentioning

confidence: 99%

Therapeutic Potential of Ursonic Acid: Comparison with Ursolic Acid

Son

Lee

2020

Biomolecules

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Plants have been used as drugs to treat human disease for centuries. Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid extracted from certain medicinal herbs such as Ziziphus jujuba. Since the pharmacological effects and associated mechanisms of UNA are not well-known, in this work, we attempt to introduce the therapeutic potential of UNA with a comparison to ursolic acid (ULA), a well-known secondary metabolite, for beneficial effects. UNA has a keto group at the C-3 position, which may provide a critical difference for the varied biological activities between UNA and ULA. Several studies previously showed that UNA exerts pharmaceutical effects similar to, or stronger than, ULA, with UNA significantly decreasing the survival and proliferation of various types of cancer cells. UNA has potential to exert inhibitory effects in parasitic protozoa that cause several tropical diseases. UNA also exerts other potential effects, including antihyperglycemic, anti-inflammatory, antiviral, and antioxidant activities. Of note, a recent study highlighted the suppressive potential of UNA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular modifications of UNA may enhance bioavailability, which is crucial for in vivo and clinical studies. In conclusion, UNA has promising potential to be developed in anticancer and antiprotozoan pharmaceuticals. In-depth investigations may increase the possibility of UNA being developed as a novel reagent for chemotherapy.

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“…The chemical changes that were made had the purpose of increasing the lipophilia and/or oxidation state at C-3. Some analogs, in particular two epimeric compounds and a ketone, all derived from OA, showed a cytotoxic activity correlated with a strong NF-κB inhibition, once again demonstrating that this factor is a molecular target of those natural compounds with therapeutic actions that we call nutraceuticals [119].…”

Section: Triterpene Acidsmentioning

confidence: 91%

Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View

Labbozzetta

Notarbartolo

Poma

2020

IJMS

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Multidrug resistance (MDR), of the innate and acquired types, is one of major problems in treating tumor diseases with a good chance of success. In this review, we examine the key role of nuclear factor-kappa B (NF-κB) to induce MDR in three tumor models characterized precisely by innate or acquired MDR, in particular triple negative breast cancer (TNBC), hepatocellular carcinoma (HCC), and acute myeloid leukemia (AML). We also present different pharmacological approaches that our group have employed to reduce the expression/activation of this transcriptional factor and thus to restore chemo-sensitivity. Finally, we examine the latest scientific evidence found by other groups, the most significant clinical trials regarding NF-κB, and new perspectives on the possibility to consider this transcriptional factor a valid drug target in neoplastic diseases.

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Cytotoxicity of oleanolic and ursolic acid derivatives toward hepatocellular carcinoma and evaluation of NF-κB involvement

Cited by 35 publications

References 30 publications

Antitumor Mechanism of the Essential Oils from Two Succulent Plants in Multidrug Resistance Leukemia Cell

Antitumor Mechanism of the Essential Oils from Two Succulent Plants in Multidrug Resistance Leukemia Cell

Therapeutic Potential of Ursonic Acid: Comparison with Ursolic Acid

Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View

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