The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat

OBJECTIVES:

To study the antinociceptive effect of single and repeated doses of resveratrol in a bone cancer pain model, and whether this effect is prevented by the Silent Information Regulator 1 (SIRT1) inhibitor selisistat.

METHODS:

The femoral intercondylar bone of BALB/c mice was injected with 1 000 000 BJ3Z cancer cells. Bone resorption and tumour mass growth (measured by in vivo X-ray and fluorescence imaging), as well as mechanical nociceptive thresholds (von Frey device) and dynamic functionality (rotarod machine), were evaluated during the following 4 weeks. Acute resveratrol (100 mg/kg i.p.) and/or selisistat(10 mg/kg s.c.) were administered on day 14. Chronic resveratrol (100 mg/kg i.p., daily) and/or selisistat (0.5 μg/h s.c., Alzet pump) were administered between days 14 and 20.

KEY FINDINGS:

Tumour growth gradually incremented until day 31, while mechanical hyperalgesia started on day 3 after cancer cell injection. Acute resveratrol increased the mechanical threshold of pain (peaking at 1.5 h), while the dynamic functionality decreased. Chronic resveratrol produced a sustained antinociceptive effect on mechanical hyperalgesia and improved the loss of dynamic functionality induced by the bone cancer tumour. Selisistat prevented all the effects of resveratrol.

CONCLUSIONS:

Acute and chronic resveratrol induces antinociceptive effect in the model of metastatic osseous oncological pain, an effect that would be mediated by SIRT1 molecular signalling.

Related Products

Cat.No.	Product Name	Information
S1541	Selisistat (EX 527)	Selisistat (EX 527, SEN0014196) is a potent and selective SIRT1 inhibitor with IC50 of 38 nM in a cell-free assay, exhibits >200-fold selectivity against SIRT2 and SIRT3. Phase 2.

Related Targets

Sirtuin