Luteolin, a Potent Anticancer Compound: From Chemistry to Cellular Interactions and Synergetic Perspectives

Abstract

Increasing rates of cancer incidence and the toxicity concerns of existing chemotherapeutic agents have intensified the research to explore more alternative routes to combat tumor. Luteolin, a flavone found in numerous fruits, vegetables, and herbs, has exhibited a number of biological activities, such as anticancer and anti-inflammatory. Luteolin inhibits tumor growth by targeting cellular processes such as apoptosis, cell-cycle progression, angiogenesis and migration. Mechanistically, luteolin causes cell death by downregulating Akt, PLK-1, cyclin-B1, cyclin-A, CDC-2, CDK-2, Bcl-2, and Bcl-xL, while upregulating BAX, caspase-3, and p21. It has also been reported to inhibit STAT3 signaling by the suppression of STAT3 activation and enhanced STAT3 protein degradation in various cancer cells. Therefore, extensive studies on the anticancer properties of luteolin reveal its promising role in chemoprevention. The present review describes all the possible cellular interactions of luteolin in cancer, along with its synergistic mode of action and nanodelivery insight.

Therapeutic Potential of Luteolin on Cancer

“…The anticancer properties of Luteolin have been related to its ability to inhibit proliferation, metastasis, and invasion of tumor cells and angiogenesis by various mechanisms, including the suppression of kinases, promotion of apoptosis, regulation of the tumor cell cycle, and reduction in transcription factors ( Figure 2 ) [ 17 ]. The induction of apoptosis has been linked with Luteolin’s anticancer properties, which involve DNA damage, regulation of redox, and protein kinases in inhibiting cancer cell proliferation ( Figure 3 ) [ 39 ].…”

“…For years, plants have been used as complementary therapies or dietary agents to manipulate cellular signaling. In light of this, many recent studies showed that among the plant-based compounds, Luteolin could suppress the process of carcinogenesis by altering different cellular events in cancer cells, promoting apoptosis; inducing cell cycle arrest; thus causing perturbation in cell cycle progression; and inhibiting proliferation, migration, and invasion of cancer cells [ 17 ]. The anticancer properties of Luteolin have been demonstrated in various cancer types in preclinical settings, and these anticancer effects were found to be regulated through its interaction with different molecular target sites and regulation of several signaling pathways in cancer cells [ 8 , 18 ]; however, no clinical studies of Luteolin have been conducted for cancer treatment yet [ 18 ].…”

From nature to therapy: Luteolin's potential as an immune system modulator in inflammatory disorders

“…It has a golden crystalline form and a C 6 –C 3 –C 6 carbon skeleton with two benzene rings connected by a heterocyclic ring. [ 17 ] Polyphenols and flavonoids protect plant cells from UV radiation, bugs, and other pests. Investigations on cultured cells, livestock populations, and human beings have shown proof that flavonoids are advantageous to the health of humans and animals.…”

“…It has a golden crystalline form and a C 6 -C 3 -C 6 carbon skeleton with two benzene rings connected by a heterocyclic ring. [17] Polyphenols and flavonoids protect plant cells from UV radiation, bugs, and other pests.…”

Structural and Anticancer Studies of Methoxyflavone Derivative from Strychnos pseudoquina A.St.-Hil. (Loganiaceae) from Brazilian Cerrado

“…These natural flavones are considered a strong starting point for the development of anticancer agents, as they can alleviate inflammation, inhibit the proliferation, migration, and invasion of cancer cells, and induce malignant cell death through mechanisms such as apoptosis and autophagy. For instance, when administered with conventional chemotherapy, luteolin has been proven to enhance anticancer effects. − …”