Luteolin Attenuates Doxorubicin-Induced Cytotoxicity to MCF-7 Human Breast Cancer Cells

Sato, Yasunori; Sasaki, Naoto; Saito, Megu; Endo, Nao; Kugawa, Fumihiko; Ueno, Akihiko

doi:10.1248/bpb.b14-00780

Cited by 53 publications

(29 citation statements)

References 28 publications

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“…For example, luteolin has been shown to induce cell cycle arrest and apoptosis, inhibit proliferation and metastatic progression, and attenuate doxorubicin-induced cytotoxicity [3, 7, 20, 22]. Although luteolin could inhibit proliferation and induce cell apoptosis in the HCC cell line HepG2 [11, 12], its role in regulating autophagy, and the relationship between cell apoptosis and autophagy, has not been elucidated in HCC.…”

Section: Discussionmentioning

confidence: 99%

“…Plants rich in luteolin have been used in Chinese traditional medicine to treat various diseases, such as hypertension, inflammatory disorders, and cancer [3, 4]. The anti-cancer activities of luteolin have been demonstrated in many cancer cells, such as pancreatic cancer, prostate cancer, breast cancer, colorectal cancer, and ovarian cancer [5-8].…”

Section: Introductionmentioning

confidence: 99%

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Luteolin Promotes Cell Apoptosis by Inducing Autophagy in Hepatocellular Carcinoma

Cao

Zhang

Cai

et al. 2017

Cell Physiol Biochem

104

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Background/Aims: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. Luteolin, a flavonoid from traditional Chinese medicine, shows anti-cancer activity in many cancer cells, including HCC. However, the mechanism underlying the action of luteolin in HCC, especially its role in regulating cell autophagy, remains unclear. In the present study, we investigated the role of luteolin in regulating cell autophagy and the role of autophagy in luteolin-induced apoptosis. Methods: The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT) was used to investigate cell viability. Flow cytometry analysis was used to detect the cell cycle and cell apoptosis. Hoechst 33342 staining was used to detect cell apoptosis. Transmission electron microscopy was used to investigate autophagy. qRT-PCR and western blotting were used to detect apoptosis- and autophagy-related mRNAs and proteins. Results: Luteolin reduced the viability of SMMC-7721 cells in a time and dose-dependent manner, and induced significant G0/G1-phase arrest. In addition, the results of flow cytometry analysis and Hoechst 33342 staining showed that luteolin treatment increased the number of apoptotic cells obviously, and the results of qRT-PCR and western blotting showed that luteolin treatment increased caspase 8 and decreased bcl-2 at the mRNA and protein levels. Furthermore, luteolin increased the number of intracellular autophagosomes, promoted LC3B-I conversion to LC3B-II, and increased Beclin 1 expression. Finally, co-treatment with the autophagy inhibitor chloroquine weakened the effects of luteolin on cell apoptosis. Conclusion: Luteolin induced apoptosis in human liver cancer SMMC-7721 cells, partially via autophagy. Thus, luteolin could be used as a regulator of autophagy in HCC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Luteolin Promotes Cell Apoptosis by Inducing Autophagy in Hepatocellular Carcinoma

Cao

Zhang

Cai

et al. 2017

Cell Physiol Biochem

104

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“…An increasing number of studies have been focusing on Chinese herb extracts, with certain compounds recently reported as molecular targeted anti-cancer drugs, such as luteolin, a novel inhibitor of RSK. Luteolin has been the focus of clinical-translational interest in anticancer treatment (31)(32)(33). In the present study, the effects of pharmacological inhibition of the RSK1 inhibitor, luteolin, on leukemic cell lines were investigated.…”

Section: A B C D Ementioning

confidence: 99%

Luteolin, a novel p90 ribosomal S6 kinase inhibitor, suppresses proliferation and migration in leukemia cells

Deng

Jiang

et al. 2017

Oncology Letters

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Abstract. Ribosomal S6 kinases (RSKs) are directly regulated by extracellular signal-regulated kinase (ERK) signaling and are implicated in cell growth, survival, motility and senescence. The present study observed that RSK1 was overexpressed in primary untreated leukemia patient bone marrow samples compared with the expression at the complete remission stage, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, a high RSK1 expression (relative expression ≥10) was associated with a significantly shorter overall survival (P=0.038) compared with that in patients with low RSK1 expression (relative expression <10). The current study also investigated the effect of luteolin, a novel p90 ribosomal S6 kinase (RSK) inhibitor extracted from Reseda odorata L., which shows strong biochemical functions including anti-allergy, anti-inflammation and anti-cancer functions, in MOLM-13 and Kasumi-1 leukemic cells. The cell viability, apoptosis and migration ability analysis were assessed by performing a cell counting kit-8 assay, Annexin V-FITC/PI double staining and migration filter assay, respectively. The results indicated that luteolin inhibited the growth of the leukemic cell lines through induction of apoptosis, while the migration ability was also suppressed. Overexpression of RSK1 by plasmid transfection was found to decrease the luteolin-induced apoptosis and migration capabilities. By contrast, knockdown of the RSK1 expression by small interfering RNA appeared to induce the same effect as luteolin on MOLM-13 and Kasumi-1 leukemic cells. In conclusion, these results suggest that luteolin inhibits leukemic cell proliferation and induces apoptosis by inhibition of the RSK1 pathways. IntroductionRibosomal S6 kinases (RSKs) are a family of serine/threonine protein kinases that are directly regulated by extracellular signal-regulated kinase (ERK) signaling. RSK1, a member of the RSK family, was initially identified as an X-linked gene in patients with mental retardation (1-3). Typically, RSK is expressed in the cerebellum during embryogenesis and silenced postnatally. Aberrant RSK signaling is integral for various types of cancer, including breast, colon and renal cancer, as well as melanoma. Li et al (4) observed that the p90 RSK2-cAMP response element-binding protein (CREB) pathway is commonly activated in diverse metastatic human cancer cells. Degen et al (5) also demonstrated this phenomenon, and further observed that overexpression of RSK3 and RSK1 supports cellular proliferation under the PI3K signaling pathway blockade. This occurs through the inhibition of apoptosis and regulation of cellular translation in squamous carcinoma cell through phosphorylation of RSK and eukaryotic translation initiation factor 4B. It is thus reported that RSK1 serves a role in squamous carcinoma cell growth and proliferation. In addition, Cohen et al (6) observed that RSK1 overexpression is associated with sunitinib resistance in renal cell carcinoma cell lines. Elf et al (7) also reported that, altho...

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“…Along with its antioxidant and anti‐inflammatory properties, luteolin has demonstrated anticancer effects in a variety of types of cancer through several mechanisms including inducing cell death, slowing cell proliferation and halting cell growth. Several studies have shown that luteolin down‐regulates Akt phosphorylation in gastric, breast, brain and other cancer cell lines .…”

mentioning

confidence: 99%

Luteolin Decreases Epidermal Growth Factor Receptor‐Mediated Cell Proliferation and Induces Apoptosis in Glioblastoma Cell Lines

Anson

Wilcox

Huseman

et al. 2018

Basic Clin Pharma Tox

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Glioblastomas are a subtype of gliomas, which are the most aggressive and deadly form of brain tumours. The epidermal growth factor receptor (EGFR) is over-expressed and amplified in glioblastomas. Luteolin is a common bioflavonoid found in a variety of fruits and vegetables. The aim of this study was to explore the molecular and biological effects of luteolin on EGF-induced cell proliferation and the potential of luteolin to induce apoptosis in glioblastoma cells. In vitro cell viability assays demonstrated that luteolin decreased cell proliferation in the presence or absence of EGF. Immunoblots revealed that luteolin decreased the protein expression levels of phosphorylated Akt, mTOR, p70S6K and MAPK in the presence of EGF. Furthermore, our results revealed the ability of luteolin to induce caspase and PARP cleavages in glioblastoma cells in addition to promoting cell cycle arrest. Our results demonstrated that luteolin has an inhibitory effect on downstream signalling molecules activated by EGFR, particularly the Akt and MAPK signalling pathways, and provided a rationale for further clinical investigation into the use of luteolin as a therapeutic molecule in the management of glioblastoma.

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Luteolin Attenuates Doxorubicin-Induced Cytotoxicity to MCF-7 Human Breast Cancer Cells

Cited by 53 publications

References 28 publications

Luteolin Promotes Cell Apoptosis by Inducing Autophagy in Hepatocellular Carcinoma

Luteolin Promotes Cell Apoptosis by Inducing Autophagy in Hepatocellular Carcinoma

Luteolin, a novel p90 ribosomal S6 kinase inhibitor, suppresses proliferation and migration in leukemia cells

Luteolin Decreases Epidermal Growth Factor Receptor‐Mediated Cell Proliferation and Induces Apoptosis in Glioblastoma Cell Lines

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