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N-Desmethyldauricine Induces Autophagic Cell Death in Apoptosis-Defective Cells via Ca2+ Mobilization

Overview of attention for article published in Frontiers in Pharmacology, June 2017
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Title
N-Desmethyldauricine Induces Autophagic Cell Death in Apoptosis-Defective Cells via Ca2+ Mobilization
Published in
Frontiers in Pharmacology, June 2017
DOI 10.3389/fphar.2017.00388
Pubmed ID
Authors

Betty Y. K. Law, Simon W. F. Mok, Juan Chen, Francesco Michelangeli, Zhi-Hong Jiang, Yu Han, Yuan Q. Qu, Alena C. L. Qiu, Su-Wei Xu, Wei-Wei Xue, Xiao-Jun Yao, Jia Y. Gao, Masood-ul-Hassan Javed, Paolo Coghi, Liang Liu, Vincent K. W. Wong

Abstract

Resistance of cancer cells to chemotherapy remains a significant problem in oncology. Mechanisms regulating programmed cell death, including apoptosis, autophagy or necrosis, in the treatment of cancers have been extensively investigated over the last few decades. Autophagy is now emerging as an important pathway in regulating cell death or survival in cancer therapy. Recent studies demonstrated variety of natural small-molecules could induce autophagic cell death in apoptosis-resistant cancer cells, therefore, discovery of novel autophagic enhancers from natural products could be a promising strategy for treatment of chemotherapy-resistant cancer. By computational virtual docking analysis, biochemical assays, and advanced live-cell imaging techniques, we have identified N-desmethyldauricine (LP-4), isolated from rhizoma of Menispermum dauricum DC as a novel inducer of autophagy. LP-4 was shown to induce autophagy via the Ulk-1-PERK and Ca(2+)/Calmodulin-dependent protein kinase kinase β (CaMKKβ)-AMPK-mTOR signaling cascades, via mobilizing calcium release through inhibition of SERCA, and importantly, lead to autophagic cell death in a panel of cancer cells, apoptosis-defective and apoptosis-resistant cells. Taken together, this study provides detailed insights into the cytotoxic mechanism of a novel autophagic compound that targeting the apoptosis resistant cancer cells, and new implication on drug discovery from natural products for drug resistant cancer therapy.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 23 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 22%
Student > Bachelor 4 17%
Student > Master 2 9%
Other 2 9%
Lecturer > Senior Lecturer 1 4%
Other 2 9%
Unknown 7 30%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 30%
Pharmacology, Toxicology and Pharmaceutical Science 2 9%
Agricultural and Biological Sciences 2 9%
Medicine and Dentistry 2 9%
Nursing and Health Professions 1 4%
Other 1 4%
Unknown 8 35%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 July 2017.
All research outputs
#18,555,330
of 22,981,247 outputs
Outputs from Frontiers in Pharmacology
#8,331
of 16,262 outputs
Outputs of similar age
#222,941
of 291,513 outputs
Outputs of similar age from Frontiers in Pharmacology
#139
of 255 outputs
Altmetric has tracked 22,981,247 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,262 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 291,513 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 255 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.