Rotenone restrains colon cancer cell viability, motility and epithelial‑mesenchymal transition and tumorigenesis in nude mice via the PI3K/AKT pathway

Abstract

Rotenone, a natural hydrophobic pesticide, has been reported to display anticancer activity in a variety of cancer cells. However, the mechanism of rotenone on colon cancer (cc) cell migration, invasion and metastasis is still unknown. In the present study, the cytotoxicity of rotenone on cc cells were detected by the cell counting Kit-8 assay and confirmed by clone formation assay. The effects of rotenone on cc cell invasion and migration activity were determined in vitro by Transwell invasion and wound healing assays, respectively. In addition, to reveal whether rotenone affected the epithelial-mesenchymal-transition (EMT) process, reverse transcription-quantitative PcR, western blotting and immunofluorescence assays were used to detect the expression of EMT markers. The expression levels of the key markers of the PI3K/AKT pathway after rotenone treatment alone or in combination with a PI3K/AKT signaling activator in cc were also detected by western blotting. Finally, the in vivo antitumor effects of rotenone were evaluated in a subcutaneous xenotransplant tumor model treated with an intraperitoneal injection of rotenone. The results of the present study demonstrated that rotenone treatment induced cc cell cytotoxicity and greater effects were observed with increasing concentrations and inhibited cell proliferation compared with untreated cells. In vitro cell function assays revealed that rotenone inhibited cc cell migration, invasion and EMT compared with untreated cells. Mechanically, the phosphorylation levels of AKT and mTOR were downregulated in rotenone-treated cc cells compared with untreated cells. Additionally, AKT and mTOR phosphorylation levels were increased by the PI3K/AKT signaling activator insulin-like growth factor 1 (IGF-1), which was reversed by rotenone treatment. The cell function assays confirmed that the IGF-1-activated cell proliferation, migration and invasion were decreased by rotenone treatment. These results indicated that rotenone affected cc cell proliferation and metastatic capabilities by inhibiting the PI3K/AKT/mTOR signaling pathway. In addition, rotenone inhibited tumor growth and metastatic capability of cc, which was confirmed in a xenograft mouse model. In conclusion, the present study revealed that rotenone inhibited cc cell viability, motility, EMT and metastasis in vitro and in vivo by inhibiting the PI3K/AKT/mTOR signaling pathway.

Investigating impacts of marine sponge derived mycothiazole and its acetylated derivative on mitochondrial function and aging

“…It is mainly used as a pesticide in agriculture and aquaculture, but its use has raised major concern because of its off-target effects on other species in the agricultural field and aquatic ecosystem (Heinz et al 2017). In human biology, it exhibits promising anticancer properties (Xiao et al 2020), but in our study, we found that it showed significant toxicity to non-cancer cells. Previous studies have shown that MTZ and 8-OAc similarly exhibit significant activity against a wide range of cancer cell types (Johnson et al 2020).…”

Identification of Effective Anticancer G-Quadruplex-Targeting Chemotypes through the Exploration of a High Diversity Library of Natural Compounds

“…Moreover, Chelidonine and Rotenone, whose anti-tumor potential has been evaluated also in recent reports [51,52], were found to produce a potent anticancer activity mediated by their capability to bind and stabilize telomeric G4 structures. In particular, demonstrating that both compounds are effective at low µM doses and show selectivity for tumor cells, our results pave the way for the design of novel and even more effective synthetic analogs of these natural compounds that could find their application field in anticancer therapies.…”

Distinct effects of different doses of kaempferol on D‑GalN/LPS‑induced ALF depend on the autophagy pathway

“…Hence, it could be hypothesized that kaempferol may also be useful for conditions characterized by dysregulated autophagy, such as HIV-associated neurodegenerative diseases. Additionally, it also can be assumed that kaempferol may be effective against diseases characterized by abnormal activation of the PIK3/Akt/mTOR pathway that benefit from mTOR inhibitors, including infectious diseases, such as HIV and severe acute respiratory syndrome coronavirus 2 ( 41 – 43 ), and autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus ( 44 – 46 ), as well as cancer ( 47 – 49 ).…”