Abstract
Among herbal medicines, magnolia bark extract, particularly its components honokiol (Hono) and magnolol (Mag), has been widely documented to have antineoplastic properties. The present study aimed to evaluate the synergism of Hono and Mag in bladder cancer therapy both in vitro and in vivo. Treatment with Mag alone at concentrations up to 80 μM failed to have an antiproliferative effect. In contrast, the combination of Hono and Mag at 40 μM decreased viability, caused cell cycle arrest and enhanced the proportion of Annexin V/7AAD-positive cells. Moreover, Mag with Hono at 40 μM induced caspase 3-dependent apoptosis and autophagy. Neither Hono nor Mag alone had an anti-migratory effect on bladder cancer cells. In contrast, Hono and Mag at 20 μM inhibited the motility of TSGH8301 and T24 cells in wound-healing and Transwell assays. The above phenomena were further confirmed by decreased phosphorylated focal adhesion kinase (p-FAK), p-paxillin, integrin β1, and integrin β3 protein levels. In a nude mouse xenograft model, Mag/Hono administration preferentially retarded T24 tumor progression, which was consistent with the results of cellular experiments. Current findings suggest Hono and Mag treatment as a potential anticancer therapy for both low- and high-grade urothelial carcinoma.
Highlights
According to World Health Organization (WHO) statistics, bladder cancer ranks as the sixth most common cancer worldwide, with approximately 430,000 new cases diagnosed each year (Burger et al, 2013)
The sub-G1 cell population was increased in the HM40 group (Figure 2A). These results showed that combined treatment with Hono and Mag caused cell cycle arrest and apoptosis in TSGH8301 and T24 cells
HM40 strongly increased p62 and LC3β expression in both bladder cancer cell lines (Figure 3B). These results indicated the involvement of mTOR and autophagy in the effects of combined treatment with Hono and Mag on human bladder cancer cells
Summary
According to World Health Organization (WHO) statistics, bladder cancer ranks as the sixth most common cancer worldwide, with approximately 430,000 new cases diagnosed each year (Burger et al, 2013). In Taiwan, bladder cancer is ninth most common cancer in men (Antoni et al, 2017). Bladder cancer can be classified as non-muscle invasive bladder cancer, which affects an estimated 75–80% of bladder cancer patients and exhibits muscle invasiveness and frequent metastasis (DeGeorge et al, 2017). Tumor recurrence is observed in an estimated 65–70% of Honokiol/Magnolol in Bladder Cancers patients (DeGeorge et al, 2017). Drug development or the discovery of new pathogenic targets is the current goal of bladder cancer research
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