Smac mimetic and oleanolic acid synergize to induce cell death in human hepatocellular carcinoma cells

Liese, Juliane; Abhari, Behnaz Ahangarian; Fulda, Simone

doi:10.1016/j.canlet.2015.04.018

Cited by 36 publications

(24 citation statements)

References 52 publications

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“…Several studies have demonstrated that oleanolic acid has a positive effect on diabetes-associated complications (13,14), however, the underlying mechanisms remain to be fully elucidated. Several studies have demonstrated the ability of oleanolic acid to normalize blood glucose levels in rodents with diet-induced obesity or diabetes through the regulation of glucose 6 phosphate and forkhead box protein O1 in the liver (15,29).…”

Section: Discussionmentioning

confidence: 99%

“…Oleanolic acid is a triterpenoid compound, which exists widely in food and Chinese herbal medicine (10). It has a variety of biological effects, including antioxidant (10), renoprotective (11), hepatoprotective (12), and anticancer effects (13). In addition, oleanolic acid, as a synergistic therapeutic drug, improves glucose and insulin homeostasis in db/db diabetic mice (14).…”

Section: Introductionmentioning

confidence: 99%

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Oleanolic acid alleviates diabetic rat carotid artery injury through the inhibition of NLRP3 inflammasome signaling pathways

Wang

et al. 2017

Molecular Medicine Reports

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The overexpression of inflammasome components is correlated with diabetes‑associated complications. Oleanolic acid is a triterpenoid compound which is important in arterial injury. The present study evaluated whether oleanolic acid improved diabetic rat carotid artery injury through the inhibition of nucleotide‑binding domain, leucine‑rich‑containing family, pyrin domain‑containing‑3 (NLRP3) inflammasomes signaling pathways. A diabetic rat model was induced using streptozotocin (60 mg/kg) and underwent carotid artery injury. Morphometric analysis was performed using hematoxylin and eosin staining. The mRNA and protein levels were assayed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. It was found that oleanolic acid (100 mg/kg/day) improved body weight, glucose metabolic disorders, neointimal hyperplasia and endothelial dysfunction in diabetic rats with carotid artery injury. In addition, oleanolic acid administration significantly downregulated the mRNA and protein expression levels of endothelin 1 in diabetic rats. Oleanolic acid decreased the intimal area and the ratio of neointima to media in diabetic rats. Serum levels of tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and IL‑18 in the oleanolic acid‑treated diabetic rats were downregulated. Consistent with the serum results, it was demonstrated that oleanolic acid administration caused a significant decrease in the levels of NLRP3, caspase‑1 and IL‑1β in the carotid arteries of diabetic rats. Taken together, these observations suggested that oleanolic acid attenuated carotid artery injury in diabetic rats and the underlying mechanism was mediated, at least partially, through the suppression of NLRP3 inflammasome signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oleanolic acid alleviates diabetic rat carotid artery injury through the inhibition of NLRP3 inflammasome signaling pathways

Wang

et al. 2017

Molecular Medicine Reports

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“…52 Multiple lines of evidence have recently reported the success of SMAC mimetics in cancer combination therapy. [53][54][55][56][57][58] Accordingly, it was worth in this study to investigate the sensitizing effect of BV6 on TNF (recombinant human TNF-a) and killer TRAIL (a highly active form of TRAIL) in different cell lines.…”

Section: Discussionmentioning

confidence: 99%

The SMAC mimetic BV6 induces cell death and sensitizes different cell lines to TNF-α and TRAIL-induced apoptosis

El-Mesery

Shaker

Elgaml

2016

Exp Biol Med (Maywood)

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The inhibitors of apoptosis proteins are implicated in promoting cancer cells survival and resistance toward immune surveillance and chemotherapy. Second mitochondria-derived activator of caspases (SMAC) mimetics are novel compounds developed to mimic the inhibitory effect of the endogenous SMAC/DIABLO on these IAPs. Here, we examined the potential effects of the novel SMAC mimetic BV6 on different human cancer cell lines. Our results indicated that BV6 was able to induce cell death in different human cancer cell lines. Mechanistically, BV6 dose dependently induced degradation of IAPs, including cIAP1 and cIAP2. This was coincided with activating the non-canonical NF-kappa B (NF-kB) pathway, as indicated by stabilizing NF-kB-inducing kinase (NIK) for p100 processing to p52. More interestingly, BV6 was able to sensitize some of the resistant cancer cell lines to apoptosis induced by the death ligands tumor necrosis factor-a (TNF-a) and TNF-related apoptosis-inducing ligand (TRAIL) that are produced by different cells of the immune system. Such cell death enhancement was mediated by inducing an additional cleavage of caspase-9 to augment that of caspase-8 induced by death ligands. This eventually led to more processing of the executioner caspase-3 and poly (ADP-ribose) polymerase (PARP). In conclusion, therapeutic targeting of IAPs by BV6 might be an effective approach to enhance cancer regression induced by immune system. Our data also open up the future possibility of using BV6 in combination with other antitumor therapies to overcome cancer drug resistance.

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“…The anticancer effects of oleanolic acid have been evaluated in many cancer types, including liver cancer [49,50,51,52], lung cancer [53,54], breast cancer [55], colon cancer [56,57,58], bladder cancer [59], prostate cancer [60], pancreatic cancer [61,62], gastric cancer [63], gallbladder cancer [64], osteosarcoma [65], hematological malignancies, e.g., leukemia [66], as well as in central nervous system cancers, such as malignant glioma [67,68]. …”

Section: Oleanolic Acid As Anticancer Agentmentioning

confidence: 99%

Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

Žiberna

Šamec

Mocan

et al. 2017

IJMS

115

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Nowadays, much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil, as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Main molecular mechanisms underlying anticancer effects of oleanolic acid are mediated by caspases, 5 adenosine monophosphate-activated protein kinase, extracellular signal-regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-κB, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3, as well as aforementioned signaling pathways . In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in the prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical.

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Smac mimetic and oleanolic acid synergize to induce cell death in human hepatocellular carcinoma cells

Cited by 36 publications

References 52 publications

Oleanolic acid alleviates diabetic rat carotid artery injury through the inhibition of NLRP3 inflammasome signaling pathways

Oleanolic acid alleviates diabetic rat carotid artery injury through the inhibition of NLRP3 inflammasome signaling pathways

The SMAC mimetic BV6 induces cell death and sensitizes different cell lines to TNF-α and TRAIL-induced apoptosis

Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

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