Formononetin Induces Apoptosis of PC‑3 Human Prostate Cancer Cells via Regulating Long Noncoding RNA H19 and the Mitochondrial Apoptosis Pathway

Objectives: We investigated the toxic effects and potential molecular mechanism of formononetin in PC‑3 prostate cancer cells to further understand the pharmacological effects of formononetin and provide more references for intensive research. Materials and Methods: PC‑3 cells were incubated with different doses of formononetin for 24 h or 48 h. After that, cell viability was measured by Cell Counting Kit‑8, and apoptosis was analyzed by Hoechst 33258 stains. The expression levels of tumor‑related factors such as long noncoding RNA (LncRNA) H19, Bax, and Bcl‑2 were determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and Western blot methods. Subsequently, PC‑3 cells were infected with a lentiviral vector to overexpress or knock down H19, and then, the expression of insulin‑like growth factor‑1 receptor (IGF‑1R) mRNA was measured by RT‑qPCR. Results: Formononetin significantly inhibited the viability of PC‑3 cells and promoted apoptosis in a time‑dose‑dependent manner. We observed that the expressions of lncRNA H19 and Bcl‑2 were significantly downregulated compared with the untreated group, while an opposite pattern was observed for Bax. According to the results of gene interaction experiments, IGF‑1R may be a downstream target of H19 in PC‑3 cells. Conclusion: Our results present evidence that formononetin induced apoptosis of PC‑3 cells by regulating lncRNA H19 and the mitochondrial apoptosis pathway. Furthermore, we put forward the hypothesis that formononetin has an interference effect on the H19/IGF‑1R pathway, which remains to be further confirmed.