Natural Products for Esophageal Cancer Therapy: From Traditional Medicine to Modern Drug Discovery

An, Jeongeun; An, Soojin; Choi, Min Chul; Jung, Ji Hoon; Kim, Bonglee

doi:10.3390/ijms232113558

Cited by 7 publications

(3 citation statements)

References 68 publications

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“…NPs can directly or indirectly affect ESC by modulating pathways like PI3K/Akt, Wnt/β-catenin, NF-κB, and ROS/MAPK through their effect on oxidative stress. These findings demonstrate that NPs possess the ability to modulate ESC development through a multi-targeted and multi-pathway approach[ 74 ]. These results establish a foundation for future investigations in cellular and animal studies, allowing for further exploration of the potential of NPs in regulating ESC development.…”

Section: Critical Considerationsmentioning

confidence: 99%

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Cao,

Zhang,

Guo

et al. 2024

World J Gastrointest Oncol

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Esophageal cancer (ESC) is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract. Although the exact pathogenesis of ESC has not been fully elucidated, excessive oxidative stress is an important characteristic that leads to the development of many cancers. Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs, which alters the growth and proliferation of ESCs and promotes their metastasis. Natural compounds, including alkaloids, terpenes, polyphenols, and xanthine compounds, can inhibit reactive oxygen species production in ESCs. These compounds reduce oxidative stress levels and subsequently inhibit the occurrence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10, superoxide dismutase, the NF-+ACY-kappa+ADs-B/MAPK pathway, and the mammalian Nrf2/ARE target pathway. Thus, targeting tumor oxidative stress has become a key focus in anti-ESC therapy. This review discusses the potential of Natural products (NPs) for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment. The findings of this review provide a reference for drug development targeting ESCs. Nonetheless, further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

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Section: Critical Considerationsmentioning

confidence: 99%

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Cao,

Zhang,

Guo

et al. 2024

World J Gastrointest Oncol

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“…ESCC exhibits more aggressive invasiveness, higher metastasis rate and more frequent recurrence, which leads to a low 5‐year survival rate (approximately 20%) 5 . Although a large number of advances in tumor therapy strategies, including radiotherapy, chemotherapy, surgery and immune therapy, the prognosis of ESCC patients remains to be improved, 6 which may be due to the lack of effective molecular targets for therapy of ESCC patients. Therefore, seeking for novel molecular targets and elucidating the potential molecular mechanisms would be valuable for improving the therapeutic efficacy of ESCC patients.…”

Section: Introductionmentioning

confidence: 99%

Glutaminase potentiates the glycolysis in esophageal squamous cell carcinoma by interacting with PDK1

Zhu,

Guan,

et al. 2024

Molecular Carcinogenesis

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Increasing evidence has demonstrated that glutaminase (GLS) as a key mitochondrial enzyme plays a pivotal role in glutaminolysis, which widely participates in glutamine metabolism serving as main energy sources and building blocks for tumor growth. However, the roles and molecular mechanisms of GLS in esophageal squamous cell carcinoma (ESCC) remains unknown. Here, we found that GLS was highly expressed in ESCC tissues and cells. GLS inhibitor CB‐839 significantly suppressed cell proliferation, colony formation, migration and invasion of ESCC cells, whereas GLS overexpression displayed the opposite effects. In addition, CB‐839 markedly suppressed glucose consumption and lactate production, coupled with the downregulation of glycolysis‐related proteins HK2, PFKM, PKM2 and LDHA, whereas GLS overexpression exhibited the adverse results. In vivo animal experiment revealed that CB‐839 dramatically suppressed tumor growth, whereas GLS overexpression promoted tumor growth in ESCC cells xenografted nude mice. Mechanistically, GLS was localized in mitochondria of ESCC cells, which interacted with PDK1 protein. CB‐839 attenuated the interaction of GLS and PDK1 in ESCC cells by suppressing PDK1 expression, which further evoked the downregulation of p‐PDHA1 (s293), however, GLS overexpression markedly enhanced the level of p‐PDHA1 (s293). These findings suggest that interaction of GLS with PDK1 accelerates the glycolysis of ESCC cells by inactivating PDH enzyme, and thus targeting GLS may be a novel therapeutic approach for ESCC patients.

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“…Natural products have many notable characteristics, such as wide efficacy and low toxicity; they have recently attracted increasing research attention as lead compounds to treat mitochondrial dysfunction-related diseases, cancer, and antimicrobial-resistant infections ( Du et al, 2021 ; An et al, 2022 ; Rahman M. A. et al, 2022 ; Bernal et al, 2022 ; Rahman M. M. et al, 2022 ; He et al, 2022 ; Liao et al, 2022 ; Nurumal et al, 2022 ; Su et al, 2022 ; Xu et al, 2022 ). Especially, the effects of many natural product on mitochondrial dysfunction-related diseases have been recently studied ( An et al, 2022 ; Rahman M. A. et al, 2022 ; Rahman M. M. et al, 2022 ). Particularly, curcumin (bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, CAS No.…”

Section: Introductionmentioning

confidence: 99%

Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods

et al. 2023

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Natural products are widely used for treating mitochondrial dysfunction-related diseases and cancers. Curcumin, a well-known natural product, can be potentially used to treat cancer. Human salt-induced kinase 3 (SIK3) is one of the target proteins for curcumin. However, the interactions between curcumin and human SIK3 have not yet been investigated in detail. In this study, we studied the binding models for the interactions between curcumin and human SIK3 using computational tools such as homology modeling, molecular docking, molecular dynamics simulations, and binding free energy calculations. The open activity loop conformation of SIK3 with the ketoenol form of curcumin was the optimal binding model. The I72, V80, A93, Y144, A145, and L195 residues played a key role for curcumin binding with human SIK3. The interactions between curcumin and human SIK3 were also investigated using the kinase assay. Moreover, curcumin exhibited an IC50 (half-maximal inhibitory concentration) value of 131 nM, and it showed significant antiproliferative activities of 9.62 ± 0.33 µM and 72.37 ± 0.37 µM against the MCF-7 and MDA-MB-23 cell lines, respectively. This study provides detailed information on the binding of curcumin with human SIK3 and may facilitate the design of novel salt-inducible kinases inhibitors.

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Natural Products for Esophageal Cancer Therapy: From Traditional Medicine to Modern Drug Discovery

Cited by 7 publications

References 68 publications

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Glutaminase potentiates the glycolysis in esophageal squamous cell carcinoma by interacting with PDK1

Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods

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