Cordyceps militaris induces apoptosis in ovarian cancer cells through TNF-α/TNFR1-mediated inhibition of NF-κB phosphorylation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-01-13

AUTHORS

Eunbi Jo, Hyun-Jin Jang, Kyeong Eun Yang, Min Su Jang, Yang Hoon Huh, Hwa-Seung Yoo, Jun Soo Park, Ik-Soon Jang, Soo Jung Park

ABSTRACT

BackgroundCordyceps militaris (L.) Fr. (C. militaris) exhibits pharmacological activities, including antitumor properties, through the regulation of the nuclear factor kappa B (NF-κB) signaling. Tumor Necrosis Factor (TNF) and TNF-α modulates cell survival and apoptosis through NF- κB signaling. However, the mechanism underlying its mode of action on the NF-κB pathway is unclear.MethodsHere, we analyzed the effect of C. militaris extract (CME) on the proliferation of ovarian cancer cells by confirming viability, morphological changes, migration assay. Additionally, CME induced apoptosis was determined by apoptosis assay and apoptotic body formation under TEM. The mechanisms of CME were determined through microarray, immunoblotting and immunocytochemistry.ResultsCME reduced the viability of cells in a dose-dependent manner and induced morphological changes. We confirmed the decrease in the migration activity of SKOV-3 cells after treatment with CME and the consequent induction of apoptosis. Immunoblotting results showed that the CME-mediated upregulation of tumor necrosis factor receptor 1 (TNFR1) expression induced apoptosis of SKOV-3 cells via the serial activation of caspases. Moreover, CME negatively modulated NF-κB activation via TNFR expression, suggestive of the activation of the extrinsic apoptotic pathway. The binding of TNF-α to TNFR results in the disassociation of IκB from NF-κB and the subsequent translocation of the active NF-κB to the nucleus. CME clearly suppressed NF-κB translocation induced by interleukin (IL-1β) from the cytosol into the nucleus. The decrease in the expression levels of B cell lymphoma (Bcl)-xL and Bcl-2 led to a marked increase in cell apoptosis.ConclusionThese results suggest that C. militaris inhibited ovarian cancer cell proliferation, survival, and migration, possibly through the coordination between TNF-α/TNFR1 signaling and NF-κB activation. Taken together, our findings provide a new insight into a novel treatment strategy for ovarian cancer using C. militaris. More... »

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http://scigraph.springernature.com/pub.10.1186/s12906-019-2780-5

DOI

http://dx.doi.org/10.1186/s12906-019-2780-5

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https://app.dimensions.ai/details/publication/pub.1124060156

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32020859


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35 schema:keywords B signaling
36 B-cell lymphoma
37 Bcl-2
38 C. militaris
39 C. militaris extracts
40 ConclusionThese results
41 Cordyceps militaris
42 Factor-Kappa B Signaling
43 IκB
44 MethodsHere
45 NF-κB
46 NF-κB activation
47 NF-κB pathway
48 NF-κB phosphorylation
49 NF-κB signaling
50 NF-κB translocation
51 SKOV-3 cells
52 TEM
53 TNFR expression
54 TNFR1
55 XL
56 action
57 activation
58 active NF-κB
59 activity
60 antitumor properties
61 apoptosis
62 apoptosis assays
63 apoptotic body formation
64 apoptotic pathway
65 assays
66 binding
67 binding of TNF
68 body formation
69 cancer
70 cancer cell proliferation
71 cancer cells
72 caspases
73 cell apoptosis
74 cell lymphoma
75 cell proliferation
76 cell survival
77 cells
78 changes
79 consequent induction
80 coordination
81 cytosol
82 decrease
83 disassociation
84 dose-dependent manner
85 effect
86 expression
87 expression levels
88 extract
89 extrinsic apoptotic pathway
90 factors
91 findings
92 formation
93 immunoblotting
94 immunoblotting results
95 immunocytochemistry
96 increase
97 induced apoptosis
98 induction
99 inhibition
100 insights
101 interleukin
102 levels
103 lymphoma
104 manner
105 marked increase
106 mechanism
107 migration
108 migration activity
109 militaris
110 mode
111 mode of action
112 modulates cell survival
113 morphological changes
114 necrosis factor
115 new insights
116 novel treatment strategies
117 nuclear factor kappa B (NF-κB) signaling
118 nucleus
119 ovarian cancer
120 ovarian cancer cell proliferation
121 ovarian cancer cells
122 pathway
123 pharmacological activities
124 phosphorylation
125 proliferation
126 properties
127 regulation
128 results
129 serial activation
130 signaling
131 strategies
132 subsequent translocation
133 survival
134 translocation
135 treatment
136 treatment strategies
137 tumor necrosis factor
138 upregulation
139 viability
140 viability of cells
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