Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

Abstract

Renal cell carcinoma (RCC) is associated with about 90% of renal malignancies, and its incidence is increasing globally. Plant-derived compounds have gained significant attention in the scientific community for their preventative and therapeutic effects on cancer. To evaluate the anticancer potential of phytocompounds for RCC, we compiled a comprehensive and systematic review of the available literature. Our work was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The literature search was performed using scholarly databases such as PubMed, Scopus, and ScienceDirect and keywords such as renal cell carcinoma, phytochemicals, cancer, tumor, proliferation, apoptosis, prevention, treatment, in vitro, in vivo, and clinical studies. Based on in vitro results, various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur-containing compounds, suppressed cell viability, proliferation and growth, showed cytotoxic activity, inhibited invasion and migration, and enhanced the efficacy of chemotherapeutic drugs in RCC. In various animal tumor models, phytochemicals suppressed renal tumor growth, reduced tumor size, and hindered angiogenesis and metastasis. The relevant antineoplastic mechanisms involved upregulation of caspases, reduction in cyclin activity, induction of cell cycle arrest and apoptosis via modulation of a plethora of cell signaling pathways. Clinical studies demonstrated a reduced risk for the development of kidney cancer and enhancement of the efficacy of chemotherapeutic drugs. Both preclinical and clinical studies displayed significant promise of utilizing phytochemicals for the prevention and treatment of RCC. Further research, confirming the mechanisms and regulatory pathways, along with randomized controlled trials, are needed to establish the use of phytochemicals in clinical practice.

Keywords: clinical studies; in vitro; in vivo; molecular mechanisms; phytochemicals; prevention; renal cancer; treatment.

Figure 1

A PRISMA flowchart summarizing the process of literature search and study selection. The total number of in vitro, in vivo, and clinical studies (136) was greater than the number of individual research papers included in our work (114), since many publications contain more than one study type (in vitro or in vivo).

Figure 2

Chemical structures of phenolic compounds that exhibited anticancer effects in RCC. Chemical structures were created and converted using ChemSpider.com (accessed on 14 May 2022).

Figure 3

Chemical structures of terpenoids that exhibited anticancer effects in RCC. Chemical structures were created and converted using ChemSpider.com (accessed on 14 May 2022).

Figure 4

Chemical structures of alkaloids that exhibited anticancer effects in RCC. Chemical structures were created and converted using ChemSpider.com (accessed on 14 May 2022).

Figure 5

Chemical structures of sulfur-containing compounds that exhibited anticancer effects in RCC. Chemical structures were created and converted using ChemSpider.com (accessed on 14 May 2022).

Figure 6

A variety of phytochemicals modulate numerous cellular pathways that are involved in oxidative stress, proliferation, apoptosis, angiogenesis, and migration implicated in renal cancer. These compounds have demonstrated the ability to alter the expression of several key components of these pathways by causing inhibition/downregulation or activation/upregulation. This figure was created using resources available at BioRender.com (accessed on 11 May 2022).