Cancer is a major cause of death worldwide with an increasing incidence rate and is considered a major public health problem. Distance
metastasis to other tissues, high toxicity, and drug resistance of
cancer cells to
chemotherapy demand novel therapeutic approaches to treat
cancer. Natural compounds from medicinal plants have been studied for
therapeutic use in various
malignancies.
Nimbolide is an active principal compound from Azadirachta indica, which is an Asian traditional medicinal plant utilized historically as a remedy for a variety of diseases due to its
antioxidant, anti-inflammatory, anti-
cancer, and antimicrobial properties. It is a
limonoid triterpene possessing potent anti-
cancer effects in various types of
cancers. It has been reported to induce multiple cytotoxic effects in
tumor cells by modulating the cell proliferation, cell cycle, apoptosis, and
metastasis by altering the various molecular signaling pathways. In the present review, we summarized all the in vitro and in vivo studies reporting the molecular targets of
nimbolide for the therapeutic approaches in different types of
cancer cells. We analyzed research publications up to September 2021 on the effect of
nimbolide in various
malignancies and the molecular mechanism of action.
Nimbolide targets different signaling pathways including
epidermal growth factor (
EGF),
vascular endothelial growth factor (
VEGF),
insulin like growth factor (IGF), Wingless and INT-1 (Wnt)/β-
catenin,
mitogen-activated protein kinases (MAPK)/c-Jun N-terminal
kinases (JNK),
phosphoinositide 3-kinase (PI3K)/AKT,
tumor necrosis factor-α (TNF-α)/
nuclear factor kappa B (NF-κβ), and
death receptor 5 (DR5) in several
cancer cells.
Nimbolide's widespread availability and absence of side effects, as well as understanding the molecular mechanism of
nimbolide's action, will be useful to develop a therapeutic agent against
cancer.