Autophagy regulation using luteolin: new insight into its anti-tumor activity

Ashrafizadeh, Milad; Ahmadi, Zahra; Farkhondeh, Tahereh; Samarghandian, Saeed

doi:10.1186/s12935-020-01634-9

Cited by 50 publications

(28 citation statements)

References 46 publications

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“…Autophagy plays a "double-edged sword" in tumor progression. Autophagy can not only eliminate misfolded proteins or damaged organelles to maintain tumor growth, but induce autophagic programmed cell death in tumor cells (Ashrafizadeh et al, 2020;Maiti and Hait, 2021). Autophagy is a dynamic process, including the formation of phagosomes and autophagosomes, the combination of autophagosomes and lysosomes to form autophagolysosomes and the degradation of autophagolysosomes.…”

Section: Discussionmentioning

confidence: 99%

Restricting Glutamine Uptake Enhances NSCLC Sensitivity to Third-Generation EGFR-TKI Almonertinib

Liu

Pang

et al. 2021

Front. Pharmacol.

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The emergence of secondary resistance is the main failure cause of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as a targeted therapy for non-small cell lung cancer (NSCLC). EGFR mutations of NSCLC cells can markedly increase glutamine transporter (SLC1A5) expression, thereby increasing glutamine metabolism. Glutamine metabolites can activate EGFR downstream signals, including mTOR, ERK1/2, STAT3, etc., which is an important cause for the decreased sensitivity of NSCLC to EGFR-TKIs. CCK8 and Annexin V/PI assays were conducted to detect the effects of Almonertinib and/or V9302 on the proliferation and apoptosis of NSCLC cells. Proteomics was used to determine the effect of Almonertinib on energy metabolism-related proteins in NSCLC. siRNA transfection was performed to study the effect of SLC1A5 down-regulation on cell proliferation. In addition, the effects of drugs on colony formation capacity were determined by colony formation assay. Immunofluorescence and Western blot were utilized to detect the apoptosis- and autophagy-related proteins expression. DAPI staining was utilized to detect the effect of drugs on the nucleus. Transmission electron microscope was used to observe the changes of submicroscopic structure such as autophagosomes and nucleus of cells. mCherry-GFP-LC3B tandem fluorescent protein was to used to detect the level of autophagy flux. Tumor-bearing nude mouse model was utilized to detect the effect of V9302 on the anti-tumor effect of Almonertinib in vivo. As a result, Almonertinib suppressed H1975 and A549 cell proliferation depended on its dosage and treatment duration, and it also induced apoptosis. A549 cells with wild-type EGFR had lower sensitivity to Almonertinib. The expression of SLC1A5 was up-regulated by stimulating with low concentration of Almonertinib in NSCLC cells. SLC1A5 was highly expressed in A549 cells with wild-type EGFR. Glutamine deletion or SLC1A5 inhibition/silencing inhibited the proliferation of NSCLC cells, and decreased cellular glutamine uptake. The combination of SLC1A5 inhibitor V9302 and Almonertinib had a synergistic inhibitory effect on the proliferation of NSCLC. V9302 enhanced the effect of Almonertinib in apoptosis-inducing in NSCLC cells. The combination of V9302 and Almonertinib might induce apoptosis by inhibiting autophagy.

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Section: Discussionmentioning

confidence: 99%

Restricting Glutamine Uptake Enhances NSCLC Sensitivity to Third-Generation EGFR-TKI Almonertinib

Liu

Pang

et al. 2021

Front. Pharmacol.

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“…The luteolin is a natural flavonoid that can suppress cancer progression via regulating autophagy [ 221 ]. The luteolin suppresses Akt/mTOR axis to reduce MMP-9 expression, impairing metastasis and invasion of breast cancer cells [ 222 ].…”

Section: Dietary Agents and Cancer Stem Cellsmentioning

confidence: 99%

“…It is worth mentioning that Res enhances LC-3II, Beclin-1 and ATG7 expression levels in triggering autophagy in CSCs and reducing breast cancer progression [ 353 ]. It is worth mentioning that autophagy has both tumor-promoting and tumor-suppressor roles in cancer [ 221 , 354 , 355 ] and its induction by Res requires more clarification.…”

Section: Dietary Agents and Cancer Stem Cellsmentioning

confidence: 99%

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

Paskeh

Asadi²,

Zabolian

et al. 2021

IJMS

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As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/β-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.

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“…Luteolin, a phase I metabolite of apigenin, is a flavone contained in different plants such as sage, carrots, and fennel [124][125][126]. Recently published papers have indicated the anti-cancer activities of luteolin in multiple cancer types by inducing autophagy or suppressing cancer cell proliferation [127,128]. According to a study, Coombs et al, the pretreatment of luteolin on breast cancer cells significantly downregulated the IFN-γ-induced PD-L1 expression [87].…”

Section: Luteolinmentioning

confidence: 99%

Phytochemicals in Cancer Immune Checkpoint Inhibitor Therapy

et al. 2021

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The interaction of immune checkpoint molecules in the tumor microenvironment reduces the anti-tumor immune response by suppressing the recognition of T cells to tumor cells. Immune checkpoint inhibitor (ICI) therapy is emerging as a promising therapeutic option for cancer treatment. However, modulating the immune system with ICIs still faces obstacles with severe immunogenic side effects and a lack of response against many cancer types. Plant-derived natural compounds offer regulation on various signaling cascades and have been applied for the treatment of multiple diseases, including cancer. Accumulated evidence provides the possibility of efficacy of phytochemicals in combinational with other therapeutic agents of ICIs, effectively modulating immune checkpoint-related signaling molecules. Recently, several phytochemicals have been reported to show the modulatory effects of immune checkpoints in various cancers in in vivo or in vitro models. This review summarizes druggable immune checkpoints and their regulatory factors. In addition, phytochemicals that are capable of suppressing PD-1/PD-L1 binding, the best-studied target of ICI therapy, were comprehensively summarized and classified according to chemical structure subgroups. It may help extend further research on phytochemicals as candidates of combinational adjuvants. Future clinical trials may validate the synergetic effects of preclinically investigated phytochemicals with ICI therapy.

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Autophagy regulation using luteolin: new insight into its anti-tumor activity

Cited by 50 publications

References 46 publications

Restricting Glutamine Uptake Enhances NSCLC Sensitivity to Third-Generation EGFR-TKI Almonertinib

Restricting Glutamine Uptake Enhances NSCLC Sensitivity to Third-Generation EGFR-TKI Almonertinib

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

Phytochemicals in Cancer Immune Checkpoint Inhibitor Therapy

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