Isoliquiritigenin induces apoptosis and autophagy and inhibits endometrial cancer growth in mice

Wu, Chi Hao; Chen, Hsin Yuan; Wang, Chia Woei; Shieh, Tzong‐Ming; Huang, Tsui-Chin; Li, Lin; Wang, Kai-Lee; Hsia, Shih Min

doi:10.18632/oncotarget.12369

Cited by 67 publications

(62 citation statements)

References 42 publications

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“…However, due to their weak solubility, instability and high toxicity, these inhibitors have little potential for clinical application (16). A recent study demonstrated that ISL significantly suppressed tumor growth in a xenograft mouse model of endometrial cancer without apparent side-effects (17). Based on these findings, it was proposed that ISL inhibited the progression of osteosarcoma by deactivating the PI3K/AKT signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Isoliquiritigenin inhibits the proliferation, apoptosis and migration of osteosarcoma cells

et al. 2019

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The overall survival rate of patients with osteosarcoma has remained unchanged for the last several decades. Therefore, novel drugs for osteosarcoma treatment are required. Isoliquiritigenin (ISL), a natural compound, has been demonstrated to inhibit the growth of various tumors. However, it is unclear whether ISL is able to inhibit the growth of osteosarcoma. In the present study, it was identified that ISL was able to inhibit the growth of the osteosarcoma cell line Saos-2 cells in vitro and in xenograft tumors primarily by attenuating tumor cell proliferation and, cell migration and promoting tumor cell apoptosis. Decreased tumor cell proliferation induced by ISL was associated with downregulation of cyclin D1 and upregulation of p53, p21 and p27. Increased tumor cell apoptosis triggered by ISL was associated with downregulation of apoptosis regulator Bcl-2, upregulation of apoptosis regulator Bax and damaged mitochondrial function evidenced by a low level of ATP-synthesis. In addition, ISL was able to inhibit the migratory capacity of Saos-2 cells by modulating the expression of matrix metalloproteinase (MMP)2 and MMP9. Mechanistic analysis revealed that the tumor growth-inhibitory effect of ISL may depend on the action of ISL on the phosphorylation of PI3K and AKT. However, it remains to be investigated whether the inhibitory effect of ISL on the migration of Saos-2 cells was associated with downregulated PI3K/AKT signaling. Overall, the present study provided evidence for the potential use of ISL against osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

Isoliquiritigenin inhibits the proliferation, apoptosis and migration of osteosarcoma cells

et al. 2019

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“…As a natural flavonoid, ISL has been shown to suppress the growth of endometrial cancer cells yet has little effect on normal cells at concentrations below 27 μM [17,18]. In addition, ISL can prevent mammary carcinogenesis while posing little toxicity to normal tissues and stem cells in mice [19].…”

Section: Discussionmentioning

confidence: 99%

“…It is also a vital performer of apoptosis, which degrades proteins that relate to cell structure, cell-signalling pathways, cell-cycle regulation, and DNA repair, resulting in cell death [25,26]. ISL-induced apoptosis has been observed in bladder cancer T24 cells, human lung cancer cells, and endometrial cancer cells [18,20,27]. Si et al [20] found that ISL induced apoptosis in bladder cancer T24 cells by enhancing the protein expression level of Bax and Caspase-3 and decreasing the level of antiapoptotic protein Bcl-2.…”

Section: Discussionmentioning

confidence: 99%

“…Si et al [20] found that ISL induced apoptosis in bladder cancer T24 cells by enhancing the protein expression level of Bax and Caspase-3 and decreasing the level of antiapoptotic protein Bcl-2. Moreover, Wu et al [18] reported that ISL markedly induced apoptosis by upregulating the cleavage of Caspase-3 and -7 and PARP expression in endometrial cancer, Ishikawa, or HEC-1A cells. In the current study, we obtained similar results since ISL promotes apoptosis in U2OS cells through decreasing the level of Bcl-2 and increasing the expression of Bax and active Caspase-3 (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Isoliquiritigenin Suppresses Osteosarcoma U2OS Cell Proliferation and Invasion by Regulating the PI3K/Akt Signalling Pathway

Chen¹,

Liu

Yang³

et al. 2018

Chemotherapy

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Aims: Isoliquiritigenin (ISL) is a flavonoid, that has been shown to have antioxidant, vasorelaxant, anti-inﬂammatory, and antitumor activities. This study aimed to explore the antitumor effect of ISL on human osteosarcoma U2OS cells and investigate the mechanism of this effect. Methods: The effect of ISL on osteosarcoma U2OS cell proliferation, invasion, migration, and apoptosis were determined by a CCK8 assay, a transwell invasion assay, a transwell migration assay, and fluorescence-activated cell sorting, respectively. In addition, the protein expression levels of Bcl2, Bax, active Caspase-3, Akt, mTOR, p70, and Cyclin D1 were detected by western blotting. Results: ISL suppressed cell proliferation, inhibited invasion and migration, and promoted apoptosis in U2OS cells. After treatment with ISL, the protein expression levels of Bax and active Caspase-3 increased, while the level of Bcl-2 declined significantly. Furthermore, the phosphorylation levels of Akt and mTOR declined significantly compared with that of the control. Conclusion: ISL could retard proliferation and promote apoptosis of U2OS cells possibly by suppressing the PI3K/Akt signalling pathway, indicating that it might be a potential therapeutic agent for osteosarcoma treatment.

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“…Previous results from several clinical and animal studies discovered that ISL inhibits colitis-associated colorectal cancer [20], endometrial cancer growth [21] and pulmonary metastasis of murine renal carcinoma cells [22], and in vitro studies have suggested that ISL has antiproliferative activity in prostate, tongue squamous, melanoma, glioma, breast, non-small-cell lung [13,16,[23][24][25][26]. In addition, some research has revealed that ISL exerts anti-invasive and anti-metastatic effects in breast and prostate cancer cells [17,27].…”

Section: Discussionmentioning

confidence: 99%

Isoliquiritigenin inhibits colorectal cancer cells HCT-116 growth by suppressing the PI3K/AKT pathway

Huang

Wei

Zhao³

et al. 2017

Open Life Sciences

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Isoliquiritigenin (ISL), a member of the flavonoids, is known to possess antitumor activity in different types of cancer including human breast cancer, hepatoma cancer, prostate cancer and others, both in vitro and in vivo. In the present study, we reported the effect of ISL on cell growth in human colorectal cancer cells HCT-116. As examined by CCK8 assays, ISL inhibited the proliferation of HCT-116 cells. Additionally, the antimigratory activity of ISL in HCT-116 cells was confirmed by trans-well chamber migration assays and invasion assays. Moreover, the results of fluorescence-activated cell sorting and Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) analysis showed that ISL induced apoptosis in HCT-116 cells. Further detection using SDS-PAGE assay revealed that ISL decreased the levels of phospho-AKT (p-AKT), phospho-mTOR (p-mTOR), Cyclin D1 and phospho-p70S6 Kinase (p-P70S6K). Collectively, these findings indicated that isoliquiritigenin induced growth-inhibition and apoptosis through downregulating of PI3K/AKT in human colorectal cancer.

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Isoliquiritigenin induces apoptosis and autophagy and inhibits endometrial cancer growth in mice

Cited by 67 publications

References 42 publications

Isoliquiritigenin inhibits the proliferation, apoptosis and migration of osteosarcoma cells

Isoliquiritigenin inhibits the proliferation, apoptosis and migration of osteosarcoma cells

Isoliquiritigenin Suppresses Osteosarcoma U2OS Cell Proliferation and Invasion by Regulating the PI3K/Akt Signalling Pathway

Isoliquiritigenin inhibits colorectal cancer cells HCT-116 growth by suppressing the PI3K/AKT pathway

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