Asiaticoside Increases Caspase-9 Activity in MCF-7 Cells and Inhibits TNF-α and IL-6 Expression in Nude Mouse Xenografts via the NF-κB Pathway.

Abstract

Background: We hypothesized that the antitumor effects of asiaticoside on breast cancer are driven by its ability to decrease the expression of tumor inflammation-promoting genes and increase apoptotic signaling. In this study, we aimed to better understand the mechanisms of action of asiaticoside as a chemical modulator or as a chemopreventive agent in breast cancer. Methods: MCF-7 cells were cultured and treated with 0, 20, 40, and 80 μM asiaticoside for 48 h. Fluorometric caspase-9, apoptosis, and gene expression analyses were conducted. For the xenograft experiments, we divided nude mice into the following 5 groups (10 animals per group): group I, control mice; group II, untreated tumor-bearing nude mice; group III, tumor-bearing nude mice treated with asiaticoside at weeks 1-2 and 4-7 and injected with MCF-7 cells at week 3; group IV, tumor-bearing nude mice injected with MCF-7 cells at week 3 and treated with asiaticoside beginning at week 6; and group V, nude mice treated with asiaticoside, as a drug control. After treatment, weight measurements were performed weekly. Tumor growth was determined and analyzed using histology and DNA and RNA isolation. Results: In MCF-7 cells, we found that asiaticoside increased caspase-9 activity. In the xenograft experiment, we found that TNF-α and IL-6 expression decreased (p < 0.001) via the NF-κB pathway. Conclusion: Overall, our data suggest that asiaticoside produces promising effects on tumor growth, progression, and tumor-associated inflammation in MCF-7 cells as well as a nude mouse MCF-7 tumor xenograft model.

• Authors: Fatma J Al-Saeedi
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 28 Issue 5 (Feb 23 2023) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 36903346 (Publication Type: Journal Article)

Chemical References

• NF-kappa B
• Tumor Necrosis Factor-alpha
• asiaticoside
• Interleukin-6
• Caspase 9

Topics

• Humans
• Mice
• Animals
• Female
• MCF-7 Cells
• NF-kappa B (metabolism)
• Mice, Nude
• Tumor Necrosis Factor-alpha (metabolism)
• Interleukin-6 (metabolism)
• Heterografts
• Cell Line, Tumor
• Caspase 9 (metabolism)
• Breast Neoplasms (drug therapy)
• Apoptosis