Promethazine inhibits proliferation and promotes apoptosis in colorectal cancer cells by suppressing the PI3K/AKT pathway

Tan, Xiaoli; Gong, Liuyun; Li, Xinyue; Zhang, Xinyue; Sun, Jiahao; Luo, Xuehui; Wang, Qi; Chen, Jie; Xie, Lin; Han, Suxia

doi:10.1016/j.biopha.2021.112174

Cited by 22 publications

(15 citation statements)

References 44 publications

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“…Among them, PTEN inhibits the growth of OS cells by regulating tumor cell proliferation, Bax by regulating apoptosis, LC3 and mTOR by regulating autophagy in tumor cells, while VEGF by regulating angiogenesis. [17] Previous studies have also found [18–21] that PI3K, Akt, PTEN, Bax, LC3, VEGF, mTOR, GSK-3, p-PI3K, p-Akt, and p-mTOR proteins are all relevant targets on the PI3K/Akt signaling pathway, while affecting the progression of OS with the help of the conduction of this pathway.…”

Section: Os-associated Signaling Pathwaymentioning

confidence: 99%

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

Liu,

Jiang,

et al. 2024

Medicine

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Osteosarcoma (OS) has a high recurrence rate, disability rate, mortality and metastasis, it brings great economic burden and psychological pressure to patients, and then seriously affects the quality of life of patients. At present, the treatment methods of OS mainly include radiotherapy, chemotherapy, surgical therapy and neoadjuvant chemotherapy combined with limb salvage surgery. These treatment methods can relieve the clinical symptoms of patients to a certain extent, and also effectively reduce the disability rate, mortality and recurrence rate of OS patients. However, because metastasis of tumor cells leads to new complications, and OS cells become resistant with prolonged drug intervention, which reduces the sensitivity of OS cells to drugs, these treatments still have some limitations. More and more studies have shown that traditional Chinese medicine (TCM) has the characteristics of “multiple targets and multiple pathways,” and can play an important role in the development of OS through several key signaling pathways, including PI3K/AKT, Wnt/β-catenin, tyrosine kinase/transcription factor 3 (JAK/STAT3), Notch, transforming growth factor-β (TGF-β)/Smad, nuclear transcription factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nuclear factor E2-related factor 2 (Nrf2), Hippo/YAP, OPG/RANK/RANKL, Hedgehog and so on. In this paper, the signaling pathways of cross-interference between active ingredients of TCM and OS were reviewed, and the development status of novel OS treatment was analyzed. The active ingredients in TCM can provide therapeutic benefits to patients by targeting the activity of signaling pathways. In addition, potential strategies for targeted therapy of OS by using ferroptosis were discussed. We hope to provide a unique insight for the in-depth research and clinical application of TCM in the fields of OS growth, metastasis and chemotherapy resistance by understanding the signaling crosstalk between active ingredients in TCM and OS.

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Section: Os-associated Signaling Pathwaymentioning

confidence: 99%

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

Liu,

Jiang,

et al. 2024

Medicine

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“…Notably, inhibition of PI3K/Akt signaling impairs progression of tumor cells and increases their sensitivity to chemotherapy (Li et al 2021a, b, c, d, e, f). Therefore, activation of PI3K/Akt signaling increases tumor progression (Qiao et al 2021; Li et al 2021a, b, c, d, e, f) and inhibition of this signaling networks using berberine (Li et al 2021a, b, c, d, e, f) or promethazine (Tan et al 2021) has been of interest in cancer therapy. The next section focuses on some of the inhibitors of PI3K/Akt signaling in cancer therapy.…”

Section: Pi3k/akt Signaling and Inhibitorsmentioning

confidence: 99%

Targeting PI3K/Akt signaling in prostate cancer therapy

Hashemi

Taheriazam

Daneii

et al. 2022

J. Cell Commun. Signal.

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Urological cancers have obtained much attention in recent years due to their mortality and morbidity. The most common and malignant tumor of urological cancers is prostate cancer that imposes high socioeconomic costs on public life and androgen‐deprivation therapy, surgery, and combination of chemotherapy and radiotherapy are employed in its treatment. PI3K/Akt signaling is an oncogenic pathway responsible for migration, proliferation and drug resistance in various cancers. In the present review, the role of PI3K/Akt signaling in prostate cancer progression is highlighted. The activation of PI3K/Akt signaling occurs in prostate cancer, while PTEN as inhibitor of PI3K/Akt shows down‐regulation. Stimulation of PI3K/Akt signaling promotes survival of prostate tumor cells and prevents apoptosis. The cell cycle progression and proliferation rate of prostate tumor cells increase by PI3K/Akt signaling induction. PI3K/Akt signaling stimulates EMT and enhances metastasis of prostate tumor cells. Silencing PI3K/Akt signaling impairs growth and metastasis of prostate tumor cells. Activation of PI3K/Akt signaling mediates drug resistance and reduces radio‐sensitivity of prostate tumor cells. Anti‐tumor compounds suppress PI3K/Akt signaling in impairing prostate tumor progression. Furthermore, upstream regulators such as miRNAs, lncRNAs and circRNAs regulate PI3K/Akt signaling and it has clinical implications for prostate cancer patients.

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“…In light of this, we present our interactive dashboard, StarGazer, which aims to address these challenges by integrating three different datatypes (i.e., disease-target association, target druggability, and target protein-protein interaction) into a novel scoring system, utilizing real-time API calls and Python-based Streamlit technology. While these types of datasets have been used for numerous repositioning studies separately ( Liu et al, 2014 ; Khaladkar et al, 2017 ; Hermawan et al, 2020 ; Wijetunga et al, 2020 ; Adikusuma et al, 2021 ; Attique et al, 2021 ; Ghoussaini et al, 2021 ; Portelli et al, 2021 ; Tan et al, 2021 ; Varghese and Majumdar, 2022 ; Zhao et al, 2022 ), StarGazer represents the first ever integration of the PheWAS catalog, Open Targets, STRING and Pharos, all of which are well-curated, well-studied, open access databases. Furthermore, computational repositioning studies focus largely on singular diseases, phenotypes or drugs, but StarGazer is equipped for flexible investigation into any of the 1,844 phenotypes and traits within the dashboard.…”

Section: Introductionmentioning

confidence: 99%

StarGazer: A Hybrid Intelligence Platform for Drug Target Prioritization and Digital Drug Repositioning Using Streamlit

et al. 2022

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Target prioritization is essential for drug discovery and repositioning. Applying computational methods to analyze and process multi-omics data to find new drug targets is a practical approach for achieving this. Despite an increasing number of methods for generating datasets such as genomics, phenomics, and proteomics, attempts to integrate and mine such datasets remain limited in scope. Developing hybrid intelligence solutions that combine human intelligence in the scientific domain and disease biology with the ability to mine multiple databases simultaneously may help augment drug target discovery and identify novel drug-indication associations. We believe that integrating different data sources using a singular numerical scoring system in a hybrid intelligent framework could help to bridge these different omics layers and facilitate rapid drug target prioritization for studies in drug discovery, development or repositioning. Herein, we describe our prototype of the StarGazer pipeline which combines multi-source, multi-omics data with a novel target prioritization scoring system in an interactive Python-based Streamlit dashboard. StarGazer displays target prioritization scores for genes associated with 1844 phenotypic traits, and is available via https://github.com/AstraZeneca/StarGazer.

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Promethazine inhibits proliferation and promotes apoptosis in colorectal cancer cells by suppressing the PI3K/AKT pathway

Cited by 22 publications

References 44 publications

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

Targeting PI3K/Akt signaling in prostate cancer therapy

StarGazer: A Hybrid Intelligence Platform for Drug Target Prioritization and Digital Drug Repositioning Using Streamlit

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