The Role of Natural Products and Their Multitargeted Approach to Treat Solid Cancer

Abstract

Natural products play a critical role in the discovery and development of numerous drugs for the treatment of various types of cancer. These phytochemicals have demonstrated anti-carcinogenic properties by interfering with the initiation, development, and progression of cancer through altering various mechanisms such as cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. Treating multifactorial diseases, such as cancer with agents targeting a single target, might lead to limited success and, in many cases, unsatisfactory outcomes. Various epidemiological studies have shown that the steady consumption of fruits and vegetables is intensely associated with a reduced risk of cancer. Since ancient period, plants, herbs, and other natural products have been used as healing agents. Likewise, most of the medicinal ingredients accessible today are originated from the natural resources. Regardless of achievements, developing bioactive compounds and drugs from natural products has remained challenging, in part because of the problem associated with large-scale sequestration and mechanistic understanding. With significant progress in the landscape of cancer therapy and the rising use of cutting-edge technologies, we may have come to a crossroads to review approaches to identify the potential natural products and investigate their therapeutic efficacy. In the present review, we summarize the recent developments in natural products-based cancer research and its application in generating novel systemic strategies with a focus on underlying molecular mechanisms in solid cancer.

Keywords: medicinal plants; natural products; phytochemicals and solid cancer.

Figure 1

Schematic representation of cancer types that could be prevented/managed by natural products (phytochemicals). IC3, Indol-3-carbinol.

Figure 2

Schematic overview of PI3K/Akt/mTOR pathway. BAD, BCL2 associated agonist of cell death; FOXO1, Forkhead box O1 protein; IRS1, Insulin receptor substrate 1; 4EBP1, Eukaryotic translation initiation factor 4E-binding protein 1; p70S6K1, p70 Ribosomal S6 kinase 1; PIP2, Phosphatidylinositol 4,5-bisphosphate; PTEN, Phosphatase, and tensin homolog deleted on chromosome 10; PDK1, 3-Phosphoinositide-dependent kinase 1; PP2A, Protein phosphatase 2A; Rheb GDP, Ras homolog enriched in brain GDP; Rheb GTP, Ras homolog enriched in brain GTP and TSC, Tuberous sclerosis complex.

Figure 3

Schematic representation of Ras/MAPK pathway. ERK, Extracellular signal-regulated kinase; GAP, GTPase-activating protein; PKC; Protein kinase C; PM, Phorbol 12-myristate 13-acetate; RSK, Ribosomal s6 kinase.

Figure 4

Depiction of important cellular pathways regulated by natural products that could be utilized for therapeutic purpose in solid cancer.

Figure 5

Schematic diagram of cellular process regulated by different phytochemicals against various cancer forms.