Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway

Wu, Xiangyu; Wang, Zitong; Jiang, Yanan; Zhou, Hao; Li, Ang; Wei, Yong-Sheng; Bao, Zhuo; Wang, Donghao; Zhao, Jimin; Chen, Xinhuan; Guo, Yaping; Dong, Zigang; Liu, Kangdong

doi:10.3389/fonc.2021.683241

Cited by 13 publications

(8 citation statements)

References 32 publications

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“…Notably, many FDA-approved drugs that target nutrient metabolism, such as metformin, thiazolidinediones, statins, specific amino acid deprivation drugs and drugs targeting protein degradation have shown significant antitumor effects in various types of cancer (15). Moreover, by screening FDA approved drug library, our previous study confirmed that tegaserod maleate suppresses the proliferation of ESCC by blocking peroxisome function and the features of tegaserod maleate make it promising candidates for cancer chemoprevention (22). However, the underlying molecular targets and related mechanism still need further illustration.…”

Section: Discussionmentioning

confidence: 85%

Tegaserod maleate suppresses the growth of gastric cancer in vivo and in vitro by targeting MEK1/2

Liu

Jiang

Wang

et al. 2022

Preprint

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Gastric cancer (GC), ranking fifth in global incidence and fourth in mortality. The current treatments for GC include surgery, chemotherapy, and radiotherapy. Although management and treatment strategies for GC have been improved over the last decade, the overall five-year survival rate remains less than 30%. Therefore, there is an urgent need to find novel therapeutic or preventive strategies that can increase GC patient survival rates. In the current study, we found that tegaserod maleate, a FDA-approved drug, could inhibit the proliferation of gastric cancer cells. Tegaserod maleate binds to MEK1 /2 and inhibits MEK1 /2 kinase activity. Moreover, the construction of CRISPER/Cas9 cell line further verified that tegaserod maleate depended on MEK1 /2 to inhibit the progress of GC. Notably, we found that tegaserod maleate suppressed tumor growth in patient-derived gastric xenograft (PDX) mouse model. We also compared tegaserod maleate with trametinib, a clinical MEK1/2 inhibitor, and comfirmed that tegaserod maleate have the same effect in inhibiting tumor volume and tumor weight. Our findings suggest that tegaserod maleate can inhibit GC proliferation by targeting MEK1/2.

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Section: Discussionmentioning

confidence: 85%

Tegaserod maleate suppresses the growth of gastric cancer in vivo and in vitro by targeting MEK1/2

Liu

Jiang

Wang

et al. 2022

Preprint

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“…Now there are some non-cancer drugs for cancer prevention or inhibition, such as cardiovascular drugs, non steroidal anti-inflammatory drugs, antipsychotics and antidepressants, antibiotics and antiviral drugs [ 30 – 32 ]. Previous studies of our research group found that antitussive agent cloperastine and 5-hydroxytryptamine 4-receptor partial agonist tegaserod maleate have a good inhibitory effect on the proliferation of ESCC and can effectively prevent the recurrence of ESCC [ 33 , 34 ]. These studies show that drug repurposing is of great significance for the development of cancer prevention drugs.…”

Section: Discussionmentioning

confidence: 99%

Oxethazaine inhibits esophageal squamous cell carcinoma proliferation and metastasis by targeting aurora kinase A

Bao

et al. 2022

Cell Death Dis

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Esophageal squamous cell carcinoma (ESCC), a malignant neoplasm with high incidence, is a severe global public health threat. The current modalities used for treating ESCC include surgery, chemotherapy, and radiotherapy. Although ESCC management and treatment strategies have improved over the last decade, the overall 5-year survival rate remains <20%. Therefore, the identification of novel therapeutic strategies that can increase ESCC patient survival rates is urgently needed. Oxethazaine, an amino-amide anesthetic agent, is mainly prescribed in combination with antacids to relieve esophagitis, dyspepsia, and other gastric disorders. In the present study, we found that oxethazaine inhibited the proliferation and migration of esophageal cancer cells. According to the results of in vitro screening and binding assays, oxethazaine binds directly to AURKA, suppresses AURKA activity, and inhibits the downstream effectors of AURKA. Notably, we found that oxethazaine suppressed tumor growth in three patient-derived esophageal xenograft mouse models and tumor metastasis in vivo. Our findings suggest that oxethazaine can inhibit ESCC proliferation and metastasis in vitro and in vivo by targeting AURKA.

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“…Studies have shown that 5-hydroxytryptamine plays a mitogenic role in colon cancer cells, and HTR4 is significantly expressed in both colon cancer tissue and cells [ 12 ]. Wu et al reported that TM inhibited esophageal squamous cell carcinoma proliferation by suppressing the peroxisome pathway [ 13 ]. Zhang et al found that TM could cause G1 cell cycle arrest, induce cell apoptosis, and inhibit the growth of a variety of cancer cells [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Tegaserod Maleate Inhibits Breast Cancer Progression and Enhances the Sensitivity of Immunotherapy

Zheng

et al. 2022

Journal of Oncology

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Background. Breast cancer (BC) is the most commonly diagnosed cancer in women worldwide. The challenge in managing this heterogeneous malignancy is that BC is highly aggressive and is always associated with chemical resistance, radiation resistance, hormone therapy resistance, and targeted therapy resistance. Therefore, there is an urgent need to find effective drugs to treat BC. Methods. Based on the Selleck drug library approved by FDA, we screened 800 drugs for anti-BC cells and found that tegaserod maleate (TM), a 5-hydroxytryptamine 4-receptor (HTR4) partial agonist had the best anti-BC effect, which was further verified. The effects of different concentrations of TM on cell proliferation, invasion, and migration were evaluated in vitro using CCK8, plate cloning, transwell, and scratch assays. The UALCAN database, Kaplan–Meier Plotter database, Human Protein Atlas, and GEPIA2 were used to explore the correlation between HTR4 expression and BC patients’ clinicopathological data as well as immune response. In vivo experiments demonstrated the effect of the TM and immunotherapy drug (anti-PD1/anti-TIGIT) combination on BC tumor growth in mice. Results. TM significantly inhibited the proliferation, invasion, and migration of BC cells, and the higher the concentration, the better the inhibition effect. HTR4 was significantly downregulated in BC tissues compared to paracancerous tissues. The downregulation of HTR4 was correlated with clinicopathological data and positively correlated with BC prognosis. Interestingly, the GEPIA2 database suggested that there was a strong positive correlation between the expression of HTR4 and effector T cells, effector memory T cells, and exhausted T cells. In vitro experiments showed that TM, anti-PD1, and anti-TIGIT could all inhibit the growth and weight of BC tumors as compared with the control group. However, when anti-PD1 or anti-TIGIT was used simultaneously with TM, the inhibition of tumors significantly exceeded that in the control group. Moreover, the combination of anti-TIGIT and TM has the best inhibitory effect. Conclusion. TM inhibited the progression of breast cancer, and its combination with anti-TIGIT could effectively inhibit tumor growth and improve the sensitivity of immunotherapy in breast cancer.

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Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway

Cited by 13 publications

References 32 publications

Tegaserod maleate suppresses the growth of gastric cancer in vivo and in vitro by targeting MEK1/2

Tegaserod maleate suppresses the growth of gastric cancer in vivo and in vitro by targeting MEK1/2

Oxethazaine inhibits esophageal squamous cell carcinoma proliferation and metastasis by targeting aurora kinase A

Tegaserod Maleate Inhibits Breast Cancer Progression and Enhances the Sensitivity of Immunotherapy

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