Natural Phytochemicals in Bladder Cancer Prevention and Therapy

Abstract

Phytochemicals are natural small-molecule compounds derived from plants that have attracted attention for their anticancer activities. Some phytochemicals have been developed as first-line anticancer drugs, such as paclitaxel and vincristine. In addition, several phytochemicals show good tumor suppression functions in various cancer types. Bladder cancer is a malignant tumor of the urinary system. To date, few specific phytochemicals have been used for bladder cancer therapy, although many have been studied in bladder cancer cells and mouse models. Therefore, it is important to collate and summarize the available information on the role of phytochemicals in the prevention and treatment of bladder cancer. In this review, we summarize the effects of several phytochemicals including flavonoids, steroids, nitrogen compounds, and aromatic substances with anticancer properties and classify the mechanism of action of phytochemicals in bladder cancer. This review will contribute to facilitating the development of new anticancer drugs and strategies for the treatment of bladder cancer using phytochemicals.

Keywords: apoptosis; bladder cancer; cell cycle; phytochemical; proliferation.

Figure 1

Schematic diagram of phytochemicals targeting molecules on bladder cancer. Generally the anticancer functions were summarized into four groups: suppression of cell cycle, inhibition of proliferation, induction of apoptosis and repression of MET. The red ovals represent upregulated molecules by phytochemicals and the blue ovals represent downregulated molecules by phytochemicals.

Figure 2

Phytochemicals induce apoptosis through upregulation of Bim, Bax, Bad, PARP, caspase 3, caspase 8 and caspase 9, as well as downregulation of Bcl-2, Bcl-xL and MCL1 in bladder cancer cells. The red ovals represent upregulated molecules by phytochemicals and the green ovals represent downregulated molecules by phytochemicals.

Figure 3

Phytochemicals inhibit metastasis by suppressing MMP2, MMP9, uPAR, Slug, and decreasing transcription factor activities including NF-κB, ZEB1 and β-catenin in bladder cancer cells. The blue ovals represent metastasis related molecules.

Figure 4

Phytochemicals inhibit bladder cancer cells proliferation by blocking cell cycle via suppressing various cyclins and CDKs, as well as upregulation of p21waf1 and p16-Ink4a in bladder cancer cells. The red ovals represent upregulated molecules by phytochemicals, and the blue ovals represent downregulated molecules by phytochemicals.