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. 2023 Oct;31(5):2541-2555.
doi: 10.1007/s10787-023-01281-2. Epub 2023 Jul 14.

Curcumin potentiates the anti-inflammatory effects of Tehranolide by modulating the STAT3/NF-κB signaling pathway in breast and ovarian cancer cell lines

Havva Afshari  1 , Shokoofe Noori  2 , Afshin Zarghi  3
Affiliations

Curcumin potentiates the anti-inflammatory effects of Tehranolide by modulating the STAT3/NF-κB signaling pathway in breast and ovarian cancer cell lines

Havva Afshari et al. Inflammopharmacology. 2023 Oct.

Erratum in

Abstract

Background: Studies have demonstrated that natural products, such as curcumin and artemisinin, possess anti-inflammatory effects, which can be beneficial for cancer treatment. Tehranolide, as a novel natural product, has a wide range of biological activities, including anti-cancer effects. However, many properties of Tehranolide, like its anti-inflammatory activity and its combination with curcumin, have not been investigated yet. This investigation examined the anti-inflammatory activity of Tehranolide, either alone or in combination with curcumin, via modulating the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and STAT3 (signal transducer and activator of transcription 3) signaling pathways in MDA-MB-231 and SKOV3, breast and ovarian cancer cell lines.

Methods: ELISA-based methods were employed to measure the pro-inflammatory cytokine levels and the NF-κB activity in lipopolysaccharide (LPS)-induced cells. The real-time PCR experiment and Griess test were performed to evaluate inducible nitric oxide synthase (iNOS) gene expression and nitrite levels, respectively. The STAT3 and NF-κB signaling pathways were investigated by Western blotting analysis. Tehranolide's anti-cancer activity was also assessed in a mouse model of breast cancer using the TUNEL (terminal deoxynucleotidyl transferase nick-end labeling) assay.

Results: Tehranolide diminished levels of pro-inflammatory cytokines in cancer cells. Additionally, it suppressed NF-κB DNA binding and STAT3 phosphorylation, reducing iNOS gene expression and nitrite production. Moreover, Western blotting showed that Tehranolide enhanced the inhibitory κB (IκBα) and Bcl-2 (B-cell lymphoma 2)-associated X (BAX) expression, and downregulated the expression of Bcl-2 proteins. Furthermore, the TUNEL assay demonstrated that Tehranolide induced apoptosis in a breast cancer mouse model. Curcumin potentiated all the anti-inflammatory effects of Tehranolide.

Conclusion: This investigation indicated for the first time that Tehranolide, either alone or in combination with curcumin, exerted its anti-inflammatory effects by suppressing NF-κB and STAT3 signaling pathways in SKOV3 and MDA-MB-231 cells.

Keywords: Breast cancer; Curcumin; Inflammation; NF-κB; Ovarian cancer; STAT3; Tehranolide.

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References

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