Incredible use of plant-derived bioactives as anticancer agents

Abstract

Cancer is a major global concern. Despite considerable advancements in cancer therapy and control, there are still large gaps and requirements for development. In recent years, various naturally occurring anticancer drugs have been derived from natural resources, such as alkaloids, glycosides, terpenes, terpenoids, flavones, and polyphenols. Plant-derived substances exhibit their anticancer potential through antiproliferative activity, cytotoxicity, apoptosis, angiogenesis and cell cycle arrest. Natural compounds can affect the molecular activity of cells through various signaling pathways, like the cell cycle pathway, STAT-3 pathway, PI3K/Akt, and Ras/MAP-kinase pathways. Capsaicin, ouabain, and lycopene show their anticancer potential through the STAT-3 pathway in breast, colorectal, pancreatic, lung, cervical, ovarian and colon cancers. Epigallocatechin gallate and emodin target the JNK protein in skin, breast, and lung cancers, while berberine, evodiamine, lycorine, and astragalin exhibit anticancer activity against breast, liver, prostate, pancreatic and skin cancers and leukemia through the PI3K/Akt and Ras/MAP-kinase pathways. In vitro/in vivo investigations revealed that secondary metabolites suppress cancer cells by causing DNA damage and activating apoptosis-inducing enzymes. After a meticulous literature review, the anti-cancer potential, mode of action, and clinical trials of 144 bioactive compounds and their synthetic analogues are included in the present work, which could pave the way for using plant-derived bioactives as anticancer agents.

Fig. 1. Flow-chart indicating the basic pathophysiology of different types of cancers.

Fig. 2. Flow chart summarizing the review methodology.

Fig. 3. Signal transducers and activators of the transcription (STAT3) pathway, Ras/Raf/MAPK (mitogen-activated protein kinase) pathway, and JNK (c-Jun N-terminal kinases) pathway in the development of cancer/tumor [JNK (c-Jun N-terminal kinases), signal transducers and activators of transcription (STAT3), vascular endothelial growth factor (VEGF), hepatocyte nuclear factor-1 alpha (HF-1 alpha), hepatocyte growth factor (HGF), B-cell lymphoma (Bcl), matrix metalloproteinases (MMP), RAF (rapidly accelerated fibrosarcoma), MEK/MAPK (mitogen activated protein kinase), ERK (extracellular signal-regulated kinase), PI3K (phosphatidylinositol-3 kinase), Akt (Akt kinase), mechanistic target of rapamycin (mTOR), nuclear factor-κB (Nf-kB), Rho GTPases (Rho), p21-activated kinases (PAK), early tumour shrinkage (ETS), FOS protooncogene (FOS), JUN protooncogene (JUN), mixed-lineage kinase (MLK), transforming growth factor-β-activated kinase 1 (TAK1), apoptosis signal-regulating kinase 1 (ASK1), nuclear factor of activated T cells (NFAT), and ETS-like protein 1 (ELK1)].

Fig. 4. Structures of isolated alkaloids.

Fig. 5. Structures of isolated glycosides.

Fig. 6. Structures of isolated miscellaneous drugs.

Fig. 7. Percentage of different categories of bioactive compounds with anticancer potential.

Fig. 8. Basic mechanism of action of some bioactive compounds in cancer management.