Prospects of compounds of herbal plants as anticancer agents: a comprehensive review from molecular pathways

Abstract

Cancer refers to the proliferation and multiplication of aberrant cells inside the human body, characterized by their capacity to proliferate and infiltrate various anatomical regions. Numerous biochemical pathways and signaling molecules have an impact on the cancer auto biogenesis process. The regulation of crucial cellular processes necessary for cell survival and proliferation, which are triggered by phytochemicals, is significantly influenced by signaling pathways. These pathways or components are regulated by phytochemicals. Medicinal plants are a significant reservoir of diverse anticancer medications employed in chemotherapy. The anticancer effects of phytochemicals are mediated by several methods, including induction of apoptosis, cessation of the cell cycle, inhibition of kinases, and prevention of carcinogenic substances. This paper analyzes the phytochemistry of seven prominent plant constituents, namely, alkaloids, tannins, flavonoids, phenols, steroids, terpenoids, and saponins, focusing on the involvement of the MAPK/ERK pathway, TNF signaling, death receptors, p53, p38, and actin dynamics. Hence, this review has examined a range of phytochemicals, encompassing their structural characteristics and potential anticancer mechanisms. It has underscored the significance of plant-derived bioactive compounds in the prevention of cancer, utilizing diverse molecular pathways. In addition, this endeavor also seeks to incentivize scientists to carry out clinical trials on anticancer medications derived from plants.

Keywords: apoptosis; cancer; herbal; molecular pathway; phytochemicals; plants.

FIGURE 1

MAPK/ERK pathway in cancer. The activation of MAPK initiates with the stimulation of receptor tyrosine kinase (RTK) in the MAPK/ERK signaling pathway. This leads to the activation of RAF kinase protein kinase activity through Ras activation. Subsequently, MEK (MEK1 and MEK2) is phosphorylated and activated by RAF kinase. Finally, ERK is activated and phosphorylated by MEK (https://www.sinobiological.com/pathways).

FIGURE 2

TNF-signaling pathways in cancer. Tumor necrosis factor (TNF) exerts its actions through the tumor necrosis factor receptor (TNFR), hence engaging in the extrinsic pathway to promote apoptosis. The interaction between the TNFR and procaspases is facilitated by adapter proteins, such as FADD and TRADD. These adapter proteins possess the capability to cleave inactive procaspases, hence activating the caspase cascade. This series of events ultimately results in the irreversible initiation of cell death (https://www.sinobiological.com/pathways).

FIGURE 3

Death receptor pathways in cancer. Activation of these receptors by specific ligands triggers the recruitment of multiple molecules to the death domain, which then initiates a signaling cascade. There are two distinct forms of death receptor signaling complexes. The first group comprises death-inducing signaling complexes (DISCs) that activate caspase-8, a crucial component in apoptotic signaling transduction. DISCs are formed at the CD95, TRAILR1, or TRAILR2 receptors. These processes involve the recruitment of various molecules that facilitate apoptotic and survival signal transduction (https://www.sinobiological.com/pathways).

FIGURE 4

p53 pathways in cancer. The p53 mechanism occurs due to various stress stimuli, such as DNA damage, nucleolar stress, metabolic stress, and oncogenic stress. p53 protein levels show stability. Proteasome-dependent degradation of p53 is facilitated by E3 ligases, which enhance ubiquitination, and cytoplasmic connections between p53 and Bcl-2 family proteins have also been observed to promote apoptosis (https://www.sinobiological.com/pathways).

FIGURE 5

p38 pathways in cancer. p38 MAPK governs the regulation of downstream targets, including different kinases, transcription factors, and cytosolic proteins. The kinases included in this study are MAPKAPK2, MAPKAPK3, PRAK, MSK1, and MNK ½. P38 phosphorylates various important transcription factors, including the tumor suppressor protein p53, CHOP (C/EBP homologous protein), STAT1 (signal transducer and activator of transcription-1), CREB (cAMP response element-binding protein), and Max/Myc complex. The p38 MAPK pathway is essential for controlling the synthesis of pro-inflammatory cytokines at both the transcriptional and translational stages (https://www.sinobiological.com/pathways).

FIGURE 6

Actin dynamics signaling pathways in cancer. The large protein tyrosine kinase family includes receptor tyrosine kinases (RTKs). Tyrosine kinase receptors, such as EGFR, PDGFR, MCSFR, IGF1R, INSR, NGFR, FGFR, VEGFR, and HGFR, modulate intracellular signals that control the cell’s response to external stimulus and are part of the Ras superfamily of tiny GTP-binding proteins that are involved in many biological processes (https://www.sinobiological.com/pathways).

FIGURE 7

Autophagy pathways in cancer. Activating mTOR (Akt and MAPK signaling) in cancer suppresses autophagy, while negative regulation (AMK and p53 signaling) enhances it. Both autophagy and apoptosis have beneficial and negative effects, and they communicate. Under nutritional constraint, autophagy aids survival. Other pro-apoptotic signals including TNF, TRAIL, and FADD trigger autophagy (https://www.sinobiological.com/pathways).

FIGURE 8

Phytochemicals as chemo-preventives and signaling molecule modulators. In the presence of phytochemicals that increase p53, decrease AKT, and cause cellular apoptosis and cell cycle arrest, tumor suppressor proteins activate the apoptotic cascade. Crosstalk between the p53, MAPK, and JNK pathways also contributes, where the AKT and mTOR pathways are downregulated in cancer cells, causing autophagy, but the presence of herbal phytochemicals can control inflammation, angiogenesis, invasion, and metastasis (Ahmed et al., 2022).