Luteolin Suppresses Teratoma Cell Growth and Induces Cell Apoptosis via Inhibiting Bcl-2

Tumor metastasis is still the leading cause of melanoma mortality. Luteolin, a natural flavonoid, is found in fruits, vegetables, and medicinal herbs. The pharmacological action and mechanism of luteolin on the metastasis of melanoma remain elusive. In this study, we investigated the effect of luteolin on A375 and B16‐F10 cell viability, migration, invasion, adhesion, and tube formation of human umbilical vein endothelial cells. Epithelial–mesenchymal transition (EMT) markers and pivotal molecules in HIF‐1α/VEGF signaling expression were analysed using western blot assays or quantitative real‐time polymerase chain reaction. Results showed that luteolin inhibits cellular proliferation in A375 and B16‐F10 melanoma cells in a time‐dependent and concentration‐dependent manner. Luteolin significantly inhibited the migratory, invasive, adhesive, and tube‐forming potential of highly metastatic A375 and B16‐F10 melanoma cells or human umbilical vein endothelial cells at sub‐IC 50 concentrations, where no significant cytotoxicity was observed. Luteolin effectively suppressed EMT by increased E‐cadherin and decreased N‐cadherin and vimentin expression both in mRNA and protein levels. Further, luteolin exerted its anti‐metastasis activity through decreasing the p‐Akt, HIF‐1α, VEGF‐A, p‐VEGFR‐2, MMP‐2, and MMP‐9 proteins expression. Overall, our findings first time suggests that HIF‐1α/VEGF signaling‐mediated EMT and angiogenesis is critically involved in anti‐metastasis effect of luteolin as a potential therapeutic candidate for melanoma.

Section: Introductionmentioning

confidence: 99%

HIF‐1α/VEGF signaling‐mediated epithelial–mesenchymal transition and angiogenesis is critically involved in anti‐metastasis effect of luteolin in melanoma cells

Wang

Shen

et al. 2019

“…As defective apoptosis is one of the preponderant causative elements for the occurrence and development of diverse malignancy, stimulation of cell apoptosis is considered a common mechanism of anticarcinogen (Sun, Yang, et al, 2022). As been seen throughout an investigation with respect to the potential roles of luteolin in ovarian teratocarcinoma, these dietary components dampened the proliferation and colony formation of PA‐1 cells in vitro and in vivo, which the mechanism intimately related to regulating the proportion of Bcl‐2/Bax (Liu et al, 2019). Molecular biology studies have shown that circular RNAs (circRNAs) circ_0000190 were upregulated in lung cancer cells and tissues.…”

Section: Therapeutic Actions In Cancermentioning

confidence: 98%

Luteolin, a flavone ingredient: Anticancer mechanisms, combined medication strategy, pharmacokinetics, clinical trials, and pharmaceutical researches

Shi,

Chen,

Gong

et al. 2023

Current pharmaceutical research is energetically excavating the pharmacotherapeutic role of herb‐derived ingredients in multiple malignancies’ targeting. Luteolin is one of the major phytochemical components that exist in various traditional Chinese medicine or medical herbs. Mounting evidence reveals that this phytoconstituent endows prominent therapeutic actions on diverse malignancies, with the underlying mechanisms, combined medication strategy, and pharmacokinetics elusive. Additionally, the clinical trial and pharmaceutical investigation of luteolin remain to be systematically delineated. The present review aimed to comprehensively summarize the updated information with regard to the anticancer mechanism, combined medication strategies, pharmacokinetics, clinical trials, and pharmaceutical researches of luteolin. The survey corroborates that luteolin executes multiple anticancer effects mainly by dampening proliferation and invasion, spurring apoptosis, intercepting cell cycle, regulating autophagy and immune, inhibiting inflammatory response, inducing ferroptosis, and pyroptosis, as well as epigenetic modification, and so on. Luteolin can be applied in combination with numerous clinical anticarcinogens and natural ingredients to synergistically enhance the therapeutic efficacy of malignancies while reducing adverse reactions. For pharmacokinetics, luteolin has an unfavorable oral bioavailability, it mainly persists in plasma as glucuronides and sulfate‐conjugates after being metabolized, and is regarded as potent inhibitors of OATP1B1 and OATP2B1, which may be messed with the pharmacokinetic interactions of miscellaneous bioactive substances in vivo. Besides, pharmaceutical innovation of luteolin with leading‐edge drug delivery systems such as host–guest complexes, nanoparticles, liposomes, nanoemulsion, microspheres, and hydrogels are beneficial to the exploitation of luteolin‐based products. Moreover, some registered clinical trials on luteolin are being carried out, yet clinical research on anticancer effects should be continuously promoted.

“…LUT inhibited tumor stemness and metastasis potential in PC and OC by targeting Wnt (Han et al, 2018) and PPP2CA/YAP (Li, Hu, et al, 2023) signaling pathways. It downregulated Bcl‐2, MMP2, MMP3, and MMP9 expressions, hindering teratoma progression (Liu et al, 2019). LUT regulated the PI3K/AKT pathway, inhibiting villus cancer cell proliferation (Lim et al, 2016) and inducing apoptosis.…”

Section: Bioactivities Of Lutmentioning

confidence: 99%

Luteolin: A promising multifunctional natural flavonoid for human diseases

Zhu,

Sun,

et al. 2024

Natural products are closely associated with human health. Luteolin (LUT), a flavonoid polyphenolic compound, is widely found in fruits, vegetables, flowers, and herbs. It is noteworthy that LUT exhibits a variety of beneficial pharmacological properties and holds significant potential for clinical applications, particularly in antitumor, anti‐convulsion, diabetes control, anti‐inflammatory, neuroprotection, anti‐oxidation, anti‐cardiovascular, and other aspects. The potential mechanism of action has been partially elucidated, including the mediation of NF‐κB, toll‐like receptor, MAPK, Wnt/β‐catenin, PI3K/Akt, AMPK/mTOR, and Nrf‐2, among others. The review that aimed to comprehensively consolidate essential information on natural sources, pharmacological effects, therapeutic and preventive potential, as well as potential mechanisms of LUT. The objective is to establish a theoretical basis for the continued development and application of LUT.