The anti-leukemic activity of a luteolin-apigenin enriched fraction from an edible and ethnomedicinal plant, Elsholtzia stachyodes, is exerted through an ER stress/autophagy/cell cycle arrest/ apoptotic cell death signaling axis

Kulaphisit, Mattapong; Pomlok, Kumpanat; Saenjum, Chalermpong; Mungkornasawakul, Pitchaya; Trisuwan, Kongkiat; Wipasa, Jiraprapa; Inta, Angkana; Smith, Duncan R.; Lithanatudom, Pathrapol

doi:10.1016/j.biopha.2023.114375

Cited by 6 publications

(1 citation statement)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Autophagy and apoptosis have a close association and they could be activated by common upstream signals during the process of cancer cell death ( Su et al, 2015 ; Chen et al, 2018 ). Even though it has been concluded in various studies that luteolin exerts anticancer potential via eliciting both apoptosis and autophagy ( Ashrafizadeh et al, 2020 ; Chen et al, 2023 ; Kulaphisit et al, 2023 ; Li et al, 2023 ), the precise mechanisms have not been identified, particularly in TNBC.…”

Section: Introductionmentioning

confidence: 99%

Luteolin inhibits triple-negative breast cancer by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling

Lin

Gao

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Triple-negative breast cancer (TNBC) is one of the most prominent neoplasm disorders and lacks efficacious treatments yet. Luteolin (3′,4′,5,7-tetrahydroxyflavone), a natural flavonoid commonly presented in plants, has been reported to delay the progression of TNBC. However, the precise mechanism is still elusive. We aimed to elucidate the inhibition and molecular regulation mechanism of luteolin on TNBC.Methods: The effects of luteolin on the biological functions of TNBC cells were first evaluated using the corresponding assays for cell counting kit-8 assay, flow cytometry, wound-healing assay, and transwell migration assay, respectively. The mechanism of luteolin on TNBC cells was then analyzed by RNA sequencing and verified by RT-qPCR, Western blot, transmission electron microscopy, etc. Finally, in vivo mouse tumor models were constructed to further confirm the effects of luteolin on TNBC.Results: Luteolin dramatically suppressed cell proliferation, invasion, and migration while favoring cell apoptosis in a dose- and time-dependent manner. In TNBC cells treated with luteolin, SGK1 and AKT3 were significantly downregulated while their downstream gene BNIP3 was upregulated. According to the results of 3D modeling, the direct binding of luteolin to SGK1 was superior to that of AKT3. The inhibition of SGK1 promoted FOXO3a translocation into the nucleus and led to the transcription of BNIP3 both in vitro and in vivo, eventually facilitating the interaction between BNIP3 and apoptosis and autophagy protein. Furthermore, the upregulation of SGK1, induced by luteolin, attenuated the apoptosis and autophagy of the TNBC.Conclusion: Luteolin inhibits TNBC by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling.

show abstract

Section: Introductionmentioning

confidence: 99%

Luteolin inhibits triple-negative breast cancer by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling

Lin

Gao

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

Luteolin: A promising multifunctional natural flavonoid for human diseases

Zhu,

Sun,

et al. 2024

Phytotherapy Research

View full text Add to dashboard Cite

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.

show abstract

Phytochemical‐mediated modulation of autophagy and endoplasmic reticulum stress as a cancer therapeutic approach

Al Azzani,

Nizami,

Magramane

et al. 2024

Phytotherapy Research

View full text Add to dashboard Cite

Autophagy and endoplasmic reticulum (ER) stress are conserved processes that generally promote survival, but can induce cell death when physiological thresholds are crossed. The pro‐survival aspects of these processes are exploited by cancer cells for tumor development and progression. Therefore, anticancer drugs targeting autophagy or ER stress to induce cell death and/or block the pro‐survival aspects are being investigated extensively. Consistently, several phytochemicals have been reported to exert their anticancer effects by modulating autophagy and/or ER stress. Various phytochemicals (e.g., celastrol, curcumin, emodin, resveratrol, among others) activate the unfolded protein response to induce ER stress‐mediated apoptosis through different pathways. Similarly, various phytochemicals induce autophagy through different mechanisms (namely mechanistic target of Rapamycin [mTOR] inhibition). However, phytochemical‐induced autophagy can function either as a cytoprotective mechanism or as programmed cell death type II. Interestingly, at times, the same phytochemical (e.g., 6‐gingerol, emodin, shikonin, among others) can induce cytoprotective autophagy or programmed cell death type II depending on cellular contexts, such as cancer type. Although there is well‐documented mechanistic interplay between autophagy and ER stress, only a one‐way modulation was noted with some phytochemicals (carnosol, capsaicin, cryptotanshinone, guangsangon E, kaempferol, and δ‐tocotrienol): ER stress‐dependent autophagy. Plant extracts are sources of potent phytochemicals and while numerous phytochemicals have been investigated in preclinical and clinical studies, the search for novel phytochemicals with anticancer effects is ongoing from plant extracts used in traditional medicine (e.g., Origanum majorana). Nonetheless, the clinical translation of phytochemicals, a promising avenue for cancer therapeutics, is hindered by several limitations that need to be addressed in future studies.

show abstract

The anti-leukemic activity of a luteolin-apigenin enriched fraction from an edible and ethnomedicinal plant, Elsholtzia stachyodes, is exerted through an ER stress/autophagy/cell cycle arrest/ apoptotic cell death signaling axis

Cited by 6 publications

References 64 publications

Luteolin inhibits triple-negative breast cancer by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling

Luteolin inhibits triple-negative breast cancer by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling

Luteolin: A promising multifunctional natural flavonoid for human diseases

Phytochemical‐mediated modulation of autophagy and endoplasmic reticulum stress as a cancer therapeutic approach

Contact Info

Product

Resources

About