Adenosine Suppresses Cholangiocarcinoma Cell Growth and Invasion in Equilibrative Nucleoside Transporters-Dependent Pathway

Lertsuwan, Kornkamon; Phoaubon, Supathra; Tasnawijitwong, Nathapol; Lertsuwan, Jomnarong

doi:10.3390/ijms21030814

Cited by 6 publications

(5 citation statements)

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“…An inhibition of CCA cell proliferation and invasion by adenosine was recently reported (20,24). This appears to involve a transporter-dependent mechanism, where adenosine is transported into the cell and converted into AMP, as shown in the model proposed in Figure 6.…”

Section: Discussionmentioning

confidence: 79%

Adenosine Induces Autophagy in Cholangiocarcinoma Cells

2021

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Background/Aim: Cholangiocarcinoma is a lethal disease with increasing incidence worldwide. New therapeutic compounds are urgently needed for this disease. Here, the inhibitory effect of adenosine on cholangiocarcinoma cells was studied. Materials and Methods: Western blot analysis was used to study autophagy and flow cytometry to analyze cell death and the cell cycle. Results: Cholangiocarcinoma and immortalized cholangiocytes responded to adenosine differently, and adenosine inhibited cholangiocarcinoma cell growth by inducing autophagy. Adenosine failed to activate adenylyl cyclase in cholangiocarcinoma cell lines, but activated this enzyme in immortalized cholangiocytes. Adenosine treatment activated AMPK and led to phosphorylation of its downstream proteins including ULK and Raptor. In addition, autophagy induced by adenosine appeared to be a survival mechanism. The combination of adenosine with autophagy inhibitors greatly increased cell death, as compared to the use of either agent alone. Interestingly, immortalized cholangiocytes were more resistant to adenosine. Conclusion: Adenosine may have potential for application in cholangiocarcinoma treatment. Materials and MethodsCell culture. The intrahepatic cholangiocarcinoma cell line, HuCCA-1, was established by Prof. Stitaya Sirisinha at Chulabhorn Research Institute ( 22) and was also purchased from Japanese Collection of Research Bioresources (JCRB) Cell Bank (Osaka, Japan). HuCCA-1 was derived from a male Thai patient whose serum was positive for the O. viverrini antigen ( 22). The RMCCA-1 cell line, established from a peripheral cholangiocarcinoma specimen surgically obtained from a male Thai patient, was kindly 3769

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Section: Discussionmentioning

confidence: 79%

Adenosine Induces Autophagy in Cholangiocarcinoma Cells

2021

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“…Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. The assay was performed according to a previously described method 26 . In brief, cells were seeded into a 96-well plate at a density of 1.0 × 10 4 cells/well and allowed to attach overnight.…”

Section: Cell Viability Assaymentioning

confidence: 99%

Activation of cannabinoid receptors in breast cancer cells improves osteoblast viability in cancer-bone interaction model while reducing breast cancer cell survival and migration

Khunluck

Lertsuwan

Chutoe

et al. 2022

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The endocannabinoid system has been postulated to help restrict cancer progression and maintain osteoblastic function during bone metastasis. Herein, the effects of cannabinoid receptor (CB) type 1 and 2 activation on breast cancer cell and osteoblast interaction were investigated by using ACEA and GW405833 as CB1 and CB2 agonists, respectively. Our results showed that breast cancer cell (MDA-MB-231)-derived conditioned media markedly decreased osteoblast-like UMR-106 cell viability. In contrast, media from MDA-MB-231 cells pre-treated with GW405833 improved UMR-106 cell viability. MDA-MB-231 cells were apparently more susceptible to both CB agonists than UMR-106 cells. Thereafter, we sought to answer the question as to how CB agonists reduced MDA-MB-231 cell virulence. Present data showed that co-activation of CB1 and CB2 exerted cytotoxic effects on MDA-MB-231 cells by increasing apoptotic cell death through suppression of the NF-κB signaling pathway in an ROS-independent mechanism. ACEA or GW405833 alone or in combination also inhibited MDA-MB-231 cell migration. Thus, it can be concluded that the endocannabinoid system is able to provide protection during breast cancer bone metastasis by interfering cancer and bone cell interaction as well as by the direct suppression of cancer cell growth and migration.

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“…Cholangiocarcinoma (CCA) is a lethal cancer of bile duct epithelial cells that is not responsive to single chemotherapeutic drugs (1). CCA is a very heterogenous disease that is resistant to nucleotide-based (2)(3)(4)(5)(6) and platinum-based (2) drugs. Incidence and mortality rates are increasing, and the disease is usually advanced at presentation.…”

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confidence: 99%

Sequence of CX-4945 and Cisplatin Administration Determines the Effectiveness of Drug Combination and Cellular Response in Cholangiocarcinoma CellsIn Vitro

et al. 2021

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Background: The incidence of cholangiocarcinoma (CCA) is increasing worldwide and current single chemotherapeutic drug treatments are ineffective. CX-4945 and cisplatin are currently in clinical trial for CCA treatment. Materials and Methods: We assessed the effects of the sequence of administration of CX-4945 and cisplatin applied in combination treatments on their efficacy in CCA cells in vitro. CCA cell viability was examined using 3-( 4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Apoptosis was examined using flow cytometry. The percentage of cells positive for phosphorylated H2A histone family member X (γ-H2AX) were measured using both flow cytometry and immunofluorescence. Results: CCA cell viability was reduced to 50% after 24 h of treatments with CX-4945 and cisplatin as single agents. Interestingly, treatment with cisplatin 6 h prior to CX-4945 treatment induced significantly more DNA damage and apoptosis than CX-4945 treatment followed by cisplatin. Unexpectedly, CX-4945 treatment followed by cisplatin was less effective than single treatment in RMCCA-1 CCA cells. In addition, a 1:1 ratio of each drug was the most effective combination in these cells. Conclusion: These data demonstrate that the combination of CX-4945 and cis platin acts additively when cisplatin is applied first, at least in part due to increased DNA damage and apoptosis. Furthermore, treatment with CX-4945 prior to cisplatin treatment reduces the efficacy of this drug combination in CCA cells.

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Adenosine Suppresses Cholangiocarcinoma Cell Growth and Invasion in Equilibrative Nucleoside Transporters-Dependent Pathway

Cited by 6 publications

References 46 publications

Adenosine Induces Autophagy in Cholangiocarcinoma Cells

Adenosine Induces Autophagy in Cholangiocarcinoma Cells

Activation of cannabinoid receptors in breast cancer cells improves osteoblast viability in cancer-bone interaction model while reducing breast cancer cell survival and migration

Sequence of CX-4945 and Cisplatin Administration Determines the Effectiveness of Drug Combination and Cellular Response in Cholangiocarcinoma CellsIn Vitro

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