Catalpol: An Iridoid Glycoside With Potential in Combating Cancer Development and Progression-A Comprehensive Review

Abstract

Catalpol, a natural iridoid glycoside known for its anti-proliferative effects, has been proposed as an anticancer compound. Catalpol targets critical processes involved in cancer cell progression, like malignant proliferation, apoptosis, and metastasis. Additionally, catalpol presents potent anti-inflammatory and antioxidant properties crucial for cancer prevention and intervention. Due to the absence of clinical trials, this review investigates twelve studies, encompassing in vitro and animal trials from reputable databases, such as PubMed, with no time restrictions. Therefore, we covered evidence from catalpol's effects against several types of cancer, including breast, liver, colorectal, lung, gastric, bladder, and ovarian cancer, as well as osteosarcoma, and assessed various outcomes related to cell viability, apoptosis, migration, and modulation of molecular mechanisms by catalpol. Notably, catalpol induced cancer cell death via induction of mitochondrial apoptosis pathways, regulation of the expression of specific microRNAs, modulation of Sirt1, Kras, RACK1, PARP, PI3K/Akt, Bcl-2, and STAT3/JAK2/Src signaling pathways, and inactivation of NF-kB and Smad 2/3 signaling pathways. Furthermore, catalpol limits cancer metastasis due to modulation of critical metalloproteinases associated with cancer migration. Catalpol also synergizes with chemotherapeutic and adjuvant agents to induce cancer control, including regorafenib in liver cancer and chloroquine in gastric cancer, promoting increased anticancer action via upregulated cancer cell apoptosis, decreased proliferation, and inhibited angiogenesis via PI3K/p-Akt/mTOR/NF-κB, VEGF/VEGFR2, and Bax signaling pathways modulation. Catalpol derivatives also gained attention. Pyrazole-, imidazole-, and hydrolyzed-based catalpol derivatives increase cancer cell apoptosis and death and decrease tumor angiogenesis through similar pathways. This review seeks to provide understanding of catalpol's anticancer effects, its mechanisms of action, and its potential as a therapeutic anticancer agent while advocating for future research conductance.

Keywords: cancer; catalpol; inflammation; metastasis; oxidative stress; phytotherapy.

FIGURE 1

Molecular structure of catalpol.

FIGURE 2

Flow diagram of the study selection process following PRISMA guidelines.

FIGURE 3

Mechanisms of cancer formation and metastasis. ECM, extracellular matrix; ROS, reactive oxygen species.

FIGURE 4

Catalpol affects angiogenesis through vascular endothelial growth factor (VEGF) production and phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) signaling. HIF‐1α, hypoxia‐inducible factor 1α; VEGFR, vascular endothelial growth factor receptor. Based on Ni et al. (2024) study.

FIGURE 5

Illustration about the mechanisms by which catalpol intervenes against gastric cancer cell growth. Based on Wang and Zhan‐Sheng (2018) study. α‐SMA, alpha‐smooth muscle actin; Bax, B‐cell lymphoma protein 2 associated x protein; Bcl‐2, B‐cell lymphoma protein 2; CDK4, cyclin‐dependent kinase 4; MMP‐2, matrix metalloproteinase 2; p27, tumor protein p27; p53, tumor protein p53; PARP, poly (ADP‐ribose) polymerase; Rhoa, Ras homolog gene family member A; ROCK1, Rho‐associated coiled‐coil kinase one; ROS, reactive oxygen species. Red arrows with the block signs mean inhibition.

FIGURE 6

Illustration about the synergism between catalpol and regorafenib against hepatocellular carcinoma. CD1, cyclin D1; NF‐kB, nuclear factor kappa b; pAkt, phosphorylated protein kinase b; PI3K, phosphatidylinositol 3‐kinase; VEGF, vascular endothelial growth factor; VEGFR2, vascular endothelial growth factor receptor 2. Red arrows with the block signs mean inhibition. Based on El‐Hanboshy et al.'s study (El‐Hanboshy et al. 2021).

FIGURE 7

A pictorial representation of the main catalpol's mechanisms of action based on the results of the included studies.