GDP Induces PANC‐1 Human Pancreatic Cancer Cell Death Preferentially under Nutrient Starvation by Inhibiting PI3K/Akt/mTOR/Autophagy Signaling Pathway

Sun, Sijia; Kim, Min Jo; Omar, Ashraf M.; Phan, Nguyễn Duy; Aoike, Mio; Awale, Suresh

doi:10.1002/cbdv.202100389

Cited by 5 publications

(4 citation statements)

References 26 publications

(39 reference statements)

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“…Here, we observed that acid-selected Panc-1 cells, in line with their extreme resistance to stress metabolic conditions [47] and chemotherapeutics, had a decreased basal cell death compared to the non-selected cells at both pH e 6.7 and 7.4, while acid selection in MiaPaCa2 cells increased basal death compared to the control cells at both pH e s (Figure 2). These results are also in accordance with other studies, which demonstrated that Panc-1 cells exhibit higher stemness features than MiaPaCa-2 cells [48].…”

Section: Discussionmentioning

confidence: 66%

Tumor Microenvironment Modulates Invadopodia Activity of Non-Selected and Acid-Selected Pancreatic Cancer Cells and Its Sensitivity to Gemcitabine and C18-Gemcitabine

Carvalho,

Audero,

Greco

et al. 2024

Cells

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Background: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with high mortality due to early metastatic dissemination and high chemoresistance. All these factors are favored by its extracellular matrix (ECM)-rich microenvironment, which is also highly hypoxic and acidic. Gemcitabine (GEM) is still the first-line therapy in PDAC. However, it is quickly deaminated to its inactive metabolite. Several GEM prodrugs have emerged to improve its cytotoxicity. Here, we analyzed how the acidic/hypoxic tumor microenvironment (TME) affects the response of PDAC cell death and invadopodia-mediated ECM proteolysis to both GEM and its C18 prodrug. Methods: For this, two PDAC cell lines, PANC-1 and Mia PaCa-2 were adapted to pHe 6.6 or not for 1 month, grown as 3D organotypic cultures and exposed to either GEM or C18 in the presence and absence of acidosis and the hypoxia inducer, deferoxamine. Results: We found that C18 has higher cytotoxic and anti-invadopodia activity than GEM in all culture conditions and especially in acid and hypoxic environments. Conclusions: We propose C18 as a more effective approach to conventional GEM in developing new therapeutic strategies overcoming PDAC chemoresistance.

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Section: Discussionmentioning

confidence: 66%

Tumor Microenvironment Modulates Invadopodia Activity of Non-Selected and Acid-Selected Pancreatic Cancer Cells and Its Sensitivity to Gemcitabine and C18-Gemcitabine

Carvalho,

Audero,

Greco

et al. 2024

Cells

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“…In earlier studies, PANC-1 cancer cells have been shown to survive for more than 3 days, even in the complete absence of essential nutrients such as glucose, amino acids, and serum. This survival capacity of cancer cells under conditions of nutrient starvation is commonly called ‘austerity’ [ 25 , 50 ]. The search for a candidate that eliminates the cancer cells’ tolerance to nutrition starvation is a unique approach to anticancer drug discovery.…”

Section: Discussionmentioning

confidence: 99%

Chemical Constituents of Callistemon subulatus and Their Anti-Pancreatic Cancer Activity against Human PANC-1 Cell Line

Maneenet

Tawila

Omar

et al. 2022

Plants

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An n-hexane extract of Callistemon subulatus was found to exhibit potent cytotoxicity against PANC-1 human pancreatic cancer cells, preferentially under nutrition starvation conditions, with a PC50 value of 6.2 µg/mL. Phytochemical investigation of this bioactive extract resulted in the isolation of fifteen compounds (1–15), including a new compound, subulatone A (–). The structure of compound 1 was elucidated using HRFABMS and NMR spectroscopic analyses. The isolated compounds were tested for their preferential cytotoxicity against the PANC-1 human pancreatic cancer cell line, using an anti-austerity strategy. Among these, myrtucommulone A (2) showed highly potent preferential cytotoxicity, with a PC50 value of 0.28 µM. Myrtucommulone A (2) was found to alter PANC-1 cell morphology, inhibit cell migration, and downregulate the PI3K/Akt/mTOR and autophagy signaling pathways in nutrient-deprived media, leading to cancer cell death. Therefore, myrtucommulone A (2) is a lead compound for anticancer drug development based on an anti-austerity strategy.

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“…Autophagy is regulated in a variety of ways, especially PI3K/AKT/mTOR pathway. The PI3K/AKT/mTOR/autophagy pathways play a crucial role in regulating tumor progression and maintaining the balance of the tumor microenvironment ( Sun et al, 2021 ; Wu et al, 2020 ; Yoshida, 2017 ; Zhang et al, 2011 ). Nevertheless, the research into the regulatory interplay between HSP90B1 and autophagy remains sparse, with the specific mechanisms of HSP90B1 action in HNSC yet to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

HSP90B1 regulates autophagy via PI3K/AKT/mTOR signaling, mediating HNSC biological behaviors

Li,

Lin,

2024

PeerJ

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Background Autophagy, a crucial cellular mechanism, facilitates the degradation and removal of misfolded proteins and impaired organelles. Recent research has increasingly highlighted the intimate connection between autophagy and heat shock proteins (HSPs) in the context of tumor development. However, the specific role and underlying mechanisms of heat shock protein 90 beta family member 1 (HSP90B1) in modulating autophagy within head and neck squamous cell carcinoma (HNSCC) remain elusive. Methods Quantitative real-time PCR (qRT-PCR), Western blot (WB), immunohistochemistry (IHC) were used to detect the expression in HNSC cell lines and tissues. The relationship between HSP90B1 and clinicopathologic features was explored based on TCGA (The Cancer Genome Atlas) data and IHC results. The biological functions of HSP90B1 were analyzed through in vitro and in vivo models to evaluate proliferation, migration, invasion, and autophagy. The mechanisms of HSP90B1 were studied using bioinformatics and WB. Results HSP90B1 was upregulated in HNSC cells and tissues. High HSP90B1 levels were associated with T-stage, M-stage, clinical stage, and poor prognosis in HNSC patients. Functionally, HSP90B1 promotes HNSC cell proliferation, migration, invasion and inhibits apoptosis. We discovered that HSP90B1 obstructs autophagy and advances HNSC progression through the PI3K/Akt/mTOR pathway. Conclusion Our study demonstrates that HSP90B1 is highly expressed in HNSC. Furthermore, HSP90B1 may regulate autophagy through the PI3K/Akt/mTOR pathway, mediating HNSC cell biological behaviors. These provide new insights into potential biomarkers and targets for HNSC therapy.

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GDP Induces PANC‐1 Human Pancreatic Cancer Cell Death Preferentially under Nutrient Starvation by Inhibiting PI3K/Akt/mTOR/Autophagy Signaling Pathway

Cited by 5 publications

References 26 publications

Tumor Microenvironment Modulates Invadopodia Activity of Non-Selected and Acid-Selected Pancreatic Cancer Cells and Its Sensitivity to Gemcitabine and C18-Gemcitabine

Tumor Microenvironment Modulates Invadopodia Activity of Non-Selected and Acid-Selected Pancreatic Cancer Cells and Its Sensitivity to Gemcitabine and C18-Gemcitabine

Chemical Constituents of Callistemon subulatus and Their Anti-Pancreatic Cancer Activity against Human PANC-1 Cell Line

HSP90B1 regulates autophagy via PI3K/AKT/mTOR signaling, mediating HNSC biological behaviors

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