Olvanil, a non-pungent vanilloid enhances the gastrointestinal toxicity of cisplatin in the ferret

Chu, Kit-Man; Ngan, Man-Piu; Wai, Man-Keung; Yeung, Chun; Andrews, Paul; Sert, Nathalie Percie du; Lin, Ge; Rudd, John A.

doi:10.1016/j.toxlet.2009.11.015

Cited by 10 publications

(6 citation statements)

References 47 publications

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“…Cisplatin, as one of the most widely used antineoplastic medications, is often used together with other anti‐cancer drugs. However, the toxicity of cisplatin is its Achilles' heel [Chu et al, ]. Increasing toxicity has been found when cisplatin is combined with other classic chemotherapeutic medications [Ajani, ].…”

Section: Discussionmentioning

confidence: 99%

Anticancer Bioactive Peptide-3 Inhibits Human Gastric Cancer Growth by Suppressing Gastric Cancer Stem Cells

Yang

et al. 2014

J. Cell. Biochem.

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In the present study, the effective components of anticancer bioactive peptide-3 (ACBP-3), a novel antitumor agent isolated from goat liver, were analyzed. The CD44 (+) fraction of the human gastric cancer cell line was isolated, and the cells within this fraction that could form spheroid colonies (SCs) were identified as gastric cancer stem cells (GCSCs). Subsequently, the antitumor effect of ACBP-3 on GCSCs was investigated in vitro and in vivo. ACBP-3 dose-dependently decreased the percentage of CD44 (+) cells, suppressed the proliferation of the SC cells and inhibited their clone-forming capacity. Tumor formation from inoculated SC cells took substantially longer when the cells were treated with ACBP-3 in vivo. ACBP-3 alone or in combination with cisplatin suppressed xenograft tumor growth. The antitumor efficacy of cisplatin, when combined with ACBP-3, was enhanced even using half of the normal cisplatin dosage. The combination of cisplatin and ACBP-3 could partially alleviate the body weight loss in the mice. Moreover, treatment with ACBP-3 alone could prevent the body weight loss in the mice. Our study indicated that ACBP-3 inhibited gastric cancer cell growth by suppressing the proliferation of CSCs. ACBP-3 could be a potential CSC-targeting agent, and combined with cisplatin therapy, might be an effective way to clinically treat patients with cancer with a lower dose and reduced toxicity.

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Section: Discussionmentioning

confidence: 99%

Anticancer Bioactive Peptide-3 Inhibits Human Gastric Cancer Growth by Suppressing Gastric Cancer Stem Cells

Yang

et al. 2014

J. Cell. Biochem.

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“…We concluded that olvanil would be unlikely to be useful clinically for the control of the gastrointestinal side effects induced by cisplatin. 117 These result were somewhat disappointing given that in previous studies, RTX 10 (μg, s.c.) given at 36 h could antagonize cisplatin (5 mg/kg, i.p. )-induced delayed emesis in ferrets.…”

Section: Introductionmentioning

confidence: 95%

“…Olvanil did not prevent either emesis or the weight loss, or negative effects on food and water consumption, but instead appeared to potentiated the cisplatin-induced inhibition of food consumption by ∼20 %. 117 While cisplatin alone was without effect on temperature, hypothermia was recorded in animals concomitantly treated with olvanil; the animals also appeared more active. We concluded that olvanil would be unlikely to be useful clinically for the control of the gastrointestinal side effects induced by cisplatin.…”

Section: Introductionmentioning

confidence: 99%

The involvement of TRPV1 in emesis and anti-emesis

et al. 2015

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Diverse transmitter systems (e.g. acetylcholine, dopamine, endocannabinoids, endorphins, glutamate, histamine, 5-hydroxytryptamine, substance P) have been implicated in the pathways by which nausea and vomiting are induced and are targets for anti-emetic drugs (e.g. 5-hydroxytryptamine3 and tachykinin NK1 antagonists). The involvement of TRPV1 in emesis was discovered in the early 1990s and may have been overlooked previously as TRPV1 pharmacology was studied in rodents (mice, rats) lacking an emetic reflex. Acute subcutaneous administration of resiniferatoxin in the ferret, dog and Suncus murinus revealed that it had “broad–spectrum” anti-emetic effects against stimuli acting via both central (vestibular system, area postrema) and peripheral (abdominal vagal afferents) inputs. One of several hypotheses discussed here is that the anti-emetic effect is due to acute depletion of substance P (or another peptide) at a critical site (e.g. nucleus tractus solitarius) in the central emetic pathway. Studies in Suncus murinus revealed a potential for a long lasting (one month) effect against the chemotherapeutic agent cisplatin. Subsequent studies using telemetry in the conscious ferret compared the anti-emetic, hypothermic and hypertensive effects of resiniferatoxin (pungent) and olvanil (non-pungent) and showed that the anti-emetic effect was present (but reduced) with olvanil which although inducing hypothermia it did not have the marked hypertensive effects of resiniferatoxin. The review concludes by discussing general insights into emetic pathways and their pharmacology revealed by these relatively overlooked studies with TRPV1 activators (pungent an non-pungent; high and low lipophilicity) and antagonists and the potential clinical utility of agents targeted at the TRPV1 system.

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“…DDP and 5-FU are representative platinum-based and fluorouracil-based chemotherapeutic drugs widely used as first-line anti-cancer agents in the clinic. However, they exert severe side effects, including myeloid suppression, hepatotoxicity, ototoxicity, gastrointestinal toxicity, nephrotoxicity, and peripheral neuropathy [ 38 ], which are exacerbated if different drugs are combined. Our previous results indicated that ACBP-3 could lower the effective dose of DDP [ 5 ] and improve the quality of life of tumor-bearing mice [ 5 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

Anticancer bioactive peptide-3 inhibits human gastric cancer growth by targeting miR-338-5p

Xing

et al. 2016

Cell Biosci

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BackgroundCancer incidence and mortality have been increasing in China, making cancer the leading cause of death since 2010 and a major public health concern in the country. Cancer stem cells have been studied in relation to the treatment of different malignancies, including gastric cancer. Anticancer bioactive peptide-3 (ACBP-3) can induce the apoptosis of gastric cancer stem cells (GCSCs) and reduce their tumorigenicity. In the present study, for the first time, we used a miRNA microarray and bioinformatics analysis to identify differentially expressed miRNAs in ACBP-3-treated GCSCs and GCSC-derived tumors in a xenograft model and functionally verified the identified miRNAs. miR-338-5p was selected based on its significant upregulation by ACBP-3 both in cultured GCSCs and in tumor tissues.ResultsmiR-338-5p was downregulated in GCSCs compared with normal gastric epithelial cells, and the ectopic restoration of miR-338-5p expression in GCSCs inhibited cell proliferation and induced apoptosis, which correlated with the upregulation of the pro-apoptotic Bcl-2 proteins BAK and BIM. We also found that ACBP-3-treated GCSCs could respond to lower effective doses of cisplatin (DDP) or 5-fluorouracil (5-FU), possibly because ACBP-3 induced the expression of miR-338-5p and the BAK and BIM proteins and promoted GCSC apoptosis.ConclusionsOur data indicate that miR-338-5p is part of an important pathway for the inhibition of human gastric cancer stem cell proliferation by ACBP-3 combined with chemotherapeutics. ACBP-3 could suppress GCSC proliferation and lower the required effective dose of cisplatin or 5-fluorouracil. Therefore, this study provides not only further evidence for the remarkable anti-tumor effect of ACBP-3 but also a possible new approach for the development of GCSC-targeting therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13578-016-0112-8) contains supplementary material, which is available to authorized users.

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Olvanil, a non-pungent vanilloid enhances the gastrointestinal toxicity of cisplatin in the ferret

Cited by 10 publications

References 47 publications

Anticancer Bioactive Peptide-3 Inhibits Human Gastric Cancer Growth by Suppressing Gastric Cancer Stem Cells

Anticancer Bioactive Peptide-3 Inhibits Human Gastric Cancer Growth by Suppressing Gastric Cancer Stem Cells

The involvement of TRPV1 in emesis and anti-emesis

Anticancer bioactive peptide-3 inhibits human gastric cancer growth by targeting miR-338-5p

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