Synthesis and antitumor activities of naturally occurring oleanolic acid triterpenoid saponins and their derivatives

Liu, Qingchao; Liu, Hongchun; Zhang, Lei; Guo, Tiantian; Wang, Peng; Geng, Meiyu; Li, Yingxia

doi:10.1016/j.ejmech.2013.04.016

Cited by 52 publications

(20 citation statements)

References 32 publications

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“…Because of their apparently safety and efficacy, triterpenoid saponins have been gaining increasing interest for cancer therapy ( Du et al, 2014 ; Singh et al, 2017 ). The anticancer triterpenoid saponins modulate numerous signaling targets related to angiogenesis, apoptosis, autophagy, cancer stem cells, inflammation, metastasis, microRNAs, multidrug resistance, proliferation, and oxidative stress ( Liu et al, 2013 ; Cheng et al, 2014 ; Chun et al, 2014 ; Du et al, 2014 ). Our previous studies have shown that Platycodin D (PD), another triterpenoid saponin, has potent activity against prostate ( Zhou et al, 2015 ) and breast/mammary gland ( Kong et al, 2016 ) cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Natural products have provided an invaluable source of therapeutic agents, especially for anticancer drug discovery. Terpenoid saponins, including the triterpenoid saponins and diterpenoid saponins identified from many herbs, have been demonstrated to have activity against human cancer cells ( Haridas et al, 2001 ; Mujoo et al, 2001 ; Liu et al, 2013 ; Cheng et al, 2014 ; Chun et al, 2014 ; Du et al, 2014 ; Zhou et al, 2015 ; Singh et al, 2017 ). We recently examined four triterpenoid saponins and one diterpenoid saponin for their antitumor effects against androgen-independent PC3 prostate cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Ophiopogonin D′, a Natural Product From Radix Ophiopogonis, Induces in Vitro and in Vivo RIPK1-Dependent and Caspase-Independent Apoptotic Death in Androgen-Independent Human Prostate Cancer Cells

Wang

Zhu

et al. 2018

Front. Pharmacol.

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Objective: The purpose of this study was to evaluate the anticancer effects of Ophiopogonin D′ (OPD′, a natural product extracted from a traditional Chinese medicine (Radix Ophiopogonis) against androgen-independent prostate cancer cells and to explore the underlying molecular mechanism(s) of action.Methods: The CCK-8 assay was used to assess the viability of prostate cancer cells. The cell morphology was examined by an ultrastructural analysis via transmission electron microscopy. Cells in apoptosis (early and late stages) were detected using an Annexin V-FITC/propidium iodide kit with a FACSCaliber flow cytometer. JC-1, a cationic lipophilic probe, was employed to measure the mitochondrial membrane potential (MMP) of PC3 cells. Changes in the protein expression of RIPK1, C-RIPK1, caspase 8, cleaved-caspase 8, Bim, Bid, caspase 10, and cleaved-caspase 10 were evaluated by Western blotting. The mRNA expression of Bim was examined by quantitative real-time reverse transcription polymerase chain reaction. Z-VAD-FMK (a caspase inhibitor) and necrostatin-1 (a specific inhibitor of RIPK1) were utilized to determine whether the cell death was mediated by RIPK1 or caspases. PC3 and DU145 xenograft models in BALB/c nude mice were used to evaluate the anticancer activity of OPD′ in vivo.Results: OPD′ was shown to exert potent anti-tumor activity against PC3 cells. It induced apoptosis via a RIPK1-related pathway, increased the protein expression levels of RIPK1 and Bim, and decreased the levels of cleaved-RIPK1, caspase 8, cleaved-caspase 8, Bid, caspase 10, and cleaved-caspase 10. OPD′ also increased the mRNA expression of Bim. The protein expression of Bim was decreased when cells were pre-treated with necrostatin-1. Treatment with OPD′ inhibited the growth of PC3 and DU145 xenograft tumors in BALB/c nude mice.Conclusion: OPD′ significantly inhibited the in vitro and in vivo growth of prostate cells via RIPK1, suggesting that OPD′ may be developed as a potential anti-prostate cancer agent.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ophiopogonin D′, a Natural Product From Radix Ophiopogonis, Induces in Vitro and in Vivo RIPK1-Dependent and Caspase-Independent Apoptotic Death in Androgen-Independent Human Prostate Cancer Cells

Wang

Zhu

et al. 2018

Front. Pharmacol.

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“…The effect of chemical modifications of the sugar moiety attached to the aglycone of OA on tumor cell growth recently was reported by Liu et al [102]. Both OA saponin and its synthetic saponins showed potent cytotoxic activity against human melanoma cancer (A375) [102]. …”

Section: In Vitro Effects Of Oa and Its Synthetic Derivatives On Cmentioning

confidence: 99%

Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

et al. 2014

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Oleanolic acid (OA, 3β-hydroxyolean-12-en-28-oic acid) is a ubiquitous pentacyclic multifunctional triterpenoid, widely found in several dietary and medicinal plants. Natural and synthetic OA derivatives can modulate multiple signaling pathways including nuclear factor-κB, AKT, signal transducer and activator of transcription 3, mammalian target of rapamycin, caspases, intercellular adhesion molecule 1, vascular endothelial growth factor, and poly (ADP-ribose) polymerase in a variety of tumor cells. Importantly, synthetic derivative of OA, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), and its C-28 methyl ester (CDDO-Me) and C28 imidazole (CDDO-Im) have demonstrated potent antiangiogenic and antitumor activities in rodent cancer models. These agents are presently under evaluation in phase I studies in cancer patients. This review summarizes the diverse molecular targets of OA and its derivatives and also provides clear evidence on their promising potential in preclinical and clinical situations.

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“…As in case of other pentacyclic triterpenes, synthetized and looked for are derivatives of the oleanolic acid, supposed to show stronger cytotoxicity and selectivity as well as better capabilities of inducing apoptosis. Such properties were evaluated for lines PC-3 (prostate cancer), MCF-7 (breast cancer), A549 (lung cancer), BGC-823 [77], HL-60 (leukemia), A375 (renal carcinoma) [78], HepG2 (gastric carcinoma) [79]. Some of the derivatives showed properties slightly worse than the oleanolic acid, some, on the other hand proved much better, which pointed to the most effective modifications.…”

Section: Cytotoxic Activity Of Triterpenesmentioning

confidence: 99%

Triterpenes as Potentially Cytotoxic Compounds

2015

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Triterpenes are compounds of natural origin, which have numerously biological activities: anti-cancer properties, anti-inflammatory, anti-oxidative, anti-viral, anti-bacterial and anti-fungal. These substances can be isolated from plants, animals or fungi. Nowadays, when neoplasms are main cause of death, triterpenes can become an alternative method for treating cancer because of their cytotoxic properties and chemopreventive activities.

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Synthesis and antitumor activities of naturally occurring oleanolic acid triterpenoid saponins and their derivatives

Cited by 52 publications

References 32 publications

Ophiopogonin D′, a Natural Product From Radix Ophiopogonis, Induces in Vitro and in Vivo RIPK1-Dependent and Caspase-Independent Apoptotic Death in Androgen-Independent Human Prostate Cancer Cells

Ophiopogonin D′, a Natural Product From Radix Ophiopogonis, Induces in Vitro and in Vivo RIPK1-Dependent and Caspase-Independent Apoptotic Death in Androgen-Independent Human Prostate Cancer Cells

Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

Triterpenes as Potentially Cytotoxic Compounds

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