Xanthoxyletin Inhibits Proliferation of Human Oral Squamous Carcinoma Cells and Induces Apoptosis, Autophagy, and Cell Cycle Arrest by Modulation of the MEK/ERK Signaling Pathway

Wen, Qingquan; Luo, Kai; Huang, Haiyan; Liao, Weiguo; Yang, Hong

doi:10.12659/msm.911697

Cited by 8 publications

(6 citation statements)

References 21 publications

(22 reference statements)

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“…Cell proliferation is predominantly regulated by the cell cycle, which is a complex network of regulatory process involving multiple signaling pathways ( 19 ). For example, T-Box transcription factor TBX3 has been indicated to function as an immortalizing gene promoting proliferation via actively repressing negative cell cycle regulators, which has been associated with the c-Myc-mediated pathway ( 20 ). Moreover, xanthoxyletin has been revealed to inhibit proliferation and induce cell cycle arrest via modulating the MEK/ERK signaling pathway ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…For example, T-Box transcription factor TBX3 has been indicated to function as an immortalizing gene promoting proliferation via actively repressing negative cell cycle regulators, which has been associated with the c-Myc-mediated pathway ( 20 ). Moreover, xanthoxyletin has been revealed to inhibit proliferation and induce cell cycle arrest via modulating the MEK/ERK signaling pathway ( 20 ). Thus, the effect of TC2N on cell cycle progression and cell cycle-related proteins was further determined The experimental results revealed that TC2N overexpression increased the percentage of cells in the S phase, and upregulated the expression levels of cyclin D1, cyclin E1 and CDK4, while TC2N knockdown achieved the opposite effects.…”

Section: Discussionmentioning

confidence: 99%

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Tac2‑N serves an oncogenic role and promotes drug resistance in human gastric cancer cells

et al. 2020

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Gastric cancer is one of the most common types of malignancy worldwide. Tac2-N (TC2N) has been reported to serve as either an oncogene or tumor suppressor in numerous different types of cancer; however, the role of TC2N in gastric cancer remains poorly understood. The present study aimed to investigate the role of TC2N in gastric cancer and reveal its regulatory mechanism. A Cell Counting Kit-8 assay was used to analyze the cell proliferation rate, while wound healing and Transwell Matrigel assays were performed to determine the cell migratory and invasive abilities, respectively. Cell cycle distribution was determined by flow cytometric analysis, and the expression levels of TC2N, P-glycoprotein (P-gp), cyclin D1, CDK4, cyclin E1, MMP2, MMP9 and N-Myc downstream regulated gene 1 were analyzed using reverse transcription-quantitative PCR or western blotting. Bioinformatics analysis revealed a high expression of TC2N in patients with gastric cancer. The experimental results revealed that TC2N expression levels were significantly unregulated in gastric cancer cell lines. The knockdown of TC2N in AGS cells significantly inhibited the cell proliferation rate and induced cell cycle arrest at the G0/G1 phase, while downregulating cyclin E1, cyclin D1 and CDK4 expression levels. The knockdown of TC2N also inhibited cell migration and invasion. Furthermore, the knockdown of TC2N improved the sensitivity of AGS cells to cisplatin, paclitaxel and 5-fluorouracil, and downregulated the protein expression levels of P-gp. By contrast, TC2N overexpression exerted the opposite effects in AGS cells. In conclusion, the findings of the present study indicated that the genetic knockdown of TC2N may inhibit cell proliferation, migration and invasion, while inducing cell cycle arrest in the G1/S phase and reversing the drug resistance of AGS cells, which may be partly through inhibiting P-gp expression levels. Thus, TC2N may serve as a novel diagnostic marker and therapeutic target for patients with gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tac2‑N serves an oncogenic role and promotes drug resistance in human gastric cancer cells

et al. 2020

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“…The xenograft model was constructed as previously described with minor modification. 20 In brief, approximately 1 × 10 6 BcaCD885 cells were subcutaneously inoculated into the flanks of each mouse. When tumor volume reached ~50 mm 3 , all mice were randomly divided into two groups (n = 8): vehicle group and control group.…”

Section: Xenograft Modelmentioning

confidence: 99%

Flavopereirine Suppresses the Progression of Human Oral Cancer by Inhibiting the JAK-STAT Signaling Pathway via Targeting LASP1

Xu¹,

Wu²,

Huang³

2021

DDDT

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Objective: Flavopereirine has been identified to be a potential anti-cancer agent in several types of human cancer. This study aimed to investigate the anti-cancer activity of flavopereirine in oral cancer. Methods: The effect of flavopereirine on cell viability of human oral cancer cell lines (BcaCD885 and Tca8113) was evaluated by MTT assay and colony formation assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Cell invasion and migration were evaluated by Transwell assay. The expression of LASP1, JAK2, p-JAK2, STST3, p-STST3, STST5 and p-STST5 was evaluated by qRT-PCR and Western blot. In addition, the xenograft mouse model was constructed to determine the anti-cancer role of flavopereirine in vivo. Results: Flavopereirine significantly inhibited cell proliferation, invasion, migration and EMT process of BcaCD885 and Tca8113 cells, while promoted cell apoptosis in vitro. Flavopereirine markedly decreased the expression levels of p-JAK2, p-STST3 and p-STST5, while increased the expression levels of LASP1. In addition, downregulation of LASP1 significantly increased the expression levels of p-JAK2, p-STAT3 and p-STAT5 compared with si-NC in BcaCD885 cells. Moreover, flavopereirine was found to decrease tumor weight and volume of xenograft tumors in vivo. Conclusion:Flavopereirine inhibited the progression of oral cancer through inactivating the JAK/STAT signaling pathway by upregulating LASP1, suggesting that flavopereirine might be a potential anti-cancer agent for oral cancer.

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“…Esculetin (20 µM) was also demonstrated to be able to suppress the proliferation of human leukemia HL-60 cells, through the induction of apoptosis, autophagy, and the arrest of the cell cycle and the Raf/Mitogen-activated protein kinase/ERK kinase (MEK)/ERK signaling pathway [195]. Similarly, xanthoxyletin (5-20 µM) inhibited the growth of SCC-1 cells by modulating MEK/ERK pathway, and by inducing apoptosis, autophagy and cell cycle arrest [196]. Recently, it was shown that osthole (7-metoxy-8-isopenthenocoumarin; 150-250 µM), alone and with TMZ, triggered autophagy in human glioblastoma multiforme (T98G) and anaplastic astrocytoma (MOGGCCM) cells, although the main type of induced death in these cells was apoptosis [197].…”

Section: Coumarinsmentioning

confidence: 99%

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

Benvenuto

Albonici

Focaccetti

et al. 2020

IJMS

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One of the hallmarks of cellular transformation is the altered mechanism of cell death. There are three main types of cell death, characterized by different morphological and biochemical features, namely apoptosis (type I), autophagic cell death (type II) and necrosis (type III). Autophagy, or self-eating, is a tightly regulated process involved in stress responses, and it is a lysosomal degradation process. The role of autophagy in cancer is controversial and has been associated with both the induction and the inhibition of tumor growth. Autophagy can exert tumor suppression through the degradation of oncogenic proteins, suppression of inflammation, chronic tissue damage and ultimately by preventing mutations and genetic instability. On the other hand, tumor cells activate autophagy for survival in cellular stress conditions. Thus, autophagy modulation could represent a promising therapeutic strategy for cancer. Several studies have shown that polyphenols, natural compounds found in foods and beverages of plant origin, can efficiently modulate autophagy in several types of cancer. In this review, we summarize the current knowledge on the effects of polyphenols on autophagy, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of polyphenols for envisioning future therapies employing polyphenols as chemoadjuvants.

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Xanthoxyletin Inhibits Proliferation of Human Oral Squamous Carcinoma Cells and Induces Apoptosis, Autophagy, and Cell Cycle Arrest by Modulation of the MEK/ERK Signaling Pathway

Cited by 8 publications

References 21 publications

Tac2‑N serves an oncogenic role and promotes drug resistance in human gastric cancer cells

Tac2‑N serves an oncogenic role and promotes drug resistance in human gastric cancer cells

Flavopereirine Suppresses the Progression of Human Oral Cancer by Inhibiting the JAK-STAT Signaling Pathway via Targeting LASP1

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

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