Chelidonine Induces Apoptosis via GADD45a-p53 Regulation in Human Pancreatic Cancer Cells

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Abstract

Chelidonium majus has been used as a traditional medicine in China and western countries for various diseases, including inflammation and cancer. However, the anti-cancer effect of chelidonine, a major compound of C. majus extracts, on pancreatic cancer remains poorly understood. In this study, we found that treatment with chelidonine inhibited proliferation of BxPC-3 and MIA PaCa-2 human pancreatic cancer cells. Annexin-V/propidium iodide staining assay showed that this growth inhibitory effect of chelidonine was induced through apoptosis. We found that chelidonine treatment upregulated mRNA levels and transcription factor activity in both cell lines. Increases in protein expression levels of p53, GADD45A, p21 and cleaved caspase-3 were also observed, with more distinct changes in MIA PaCa-2 cells compared to the BxPC-3 cells. These results suggest that chelidonine induces pancreatic cancer apoptosis through the p53 and GADD45A pathways. Our findings provide new insights into the use of chelidonine for the treatment of pancreatic cancer.

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TopHat: discovering splice junctions with RNA-Seq

Cole Trapnell, Lior Pachter, Steven Salzberg (2011)

Motivation: A new protocol for sequencing the messenger RNA in a cell, known as RNA-Seq, generates millions of short sequence fragments in a single run. These fragments, or ‘reads’, can be used to measure levels of gene expression and to identify novel splice variants of genes. However, current software for aligning RNA-Seq data to a genome relies on known splice junctions and cannot identify novel ones. TopHat is an efficient read-mapping algorithm designed to align reads from an RNA-Seq experiment to a reference genome without relying on known splice sites. Results: We mapped the RNA-Seq reads from a recent mammalian RNA-Seq experiment and recovered more than 72% of the splice junctions reported by the annotation-based software from that study, along with nearly 20 000 previously unreported junctions. The TopHat pipeline is much faster than previous systems, mapping nearly 2.2 million reads per CPU hour, which is sufficient to process an entire RNA-Seq experiment in less than a day on a standard desktop computer. We describe several challenges unique to ab initio splice site discovery from RNA-Seq reads that will require further algorithm development. Availability: TopHat is free, open-source software available from http://tophat.cbcb.umd.edu Contact: cole@cs.umd.edu Supplementary information: Supplementary data are available at Bioinformatics online.

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Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors

Prashanth Rawla, Tagore Sunkara, Vinaya Gaduputi (2019)

Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide. However, its toll is higher in more developed countries. Reasons for vast differences in mortality rates of pancreatic cancer are not completely clear yet, but it may be due to lack of appropriate diagnosis, treatment and cataloging of cancer cases. Because patients seldom exhibit symptoms until an advanced stage of the disease, pancreatic cancer remains one of the most lethal malignant neoplasms that caused 432,242 new deaths in 2018 (GLOBOCAN 2018 estimates). Globally, 458,918 new cases of pancreatic cancer have been reported in 2018, and 355,317 new cases are estimated to occur until 2040. Despite advancements in the detection and management of pancreatic cancer, the 5-year survival rate still stands at 9% only. To date, the causes of pancreatic carcinoma are still insufficiently known, although certain risk factors have been identified, such as tobacco smoking, diabetes mellitus, obesity, dietary factors, alcohol abuse, age, ethnicity, family history and genetic factors, Helicobacter pylori infection, non-O blood group and chronic pancreatitis. In general population, screening of large groups is not considered useful to detect the disease at its early stage, although newer techniques and the screening of tightly targeted groups (especially of those with family history), are being evaluated. Primary prevention is considered of utmost importance. Up-to-date statistics on pancreatic cancer occurrence and outcome along with a better understanding of the etiology and identifying the causative risk factors are essential for the primary prevention of this disease.

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Improving RNA-Seq expression estimates by correcting for fragment bias

Adam Roberts, Cole Trapnell, Julie Donaghey … (2011)

The biochemistry of RNA-Seq library preparation results in cDNA fragments that are not uniformly distributed within the transcripts they represent. This non-uniformity must be accounted for when estimating expression levels, and we show how to perform the needed corrections using a likelihood based approach. We find improvements in expression estimates as measured by correlation with independently performed qRT-PCR and show that correction of bias leads to improved replicability of results across libraries and sequencing technologies.

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Author and article information

Journal

Journal ID (nlm-ta): Integr Cancer Ther

Journal ID (iso-abbrev): Integr Cancer Ther

Journal ID (publisher-id): ICT

Journal ID (hwp): spict

Title: Integrative Cancer Therapies

Publisher: SAGE Publications (Sage CA: Los Angeles, CA )

ISSN (Print): 1534-7354

ISSN (Electronic): 1552-695X

Publication date (Electronic): 22 April 2021

Publication date Collection: 2021

Volume: 20

Electronic Location Identifier: 15347354211006191

Affiliations

[1 ]Korea Basic Science Institute, Daejeon, Republic of Korea

[2 ]Sungkyunkwan University, Suwon, Republic of Korea

[3 ]Daejeon Korean Medicine Hospital of Daejeon University, Seoul, Republic of Korea

[4 ]Hanyang University, Seoul, Republic of Korea

[5 ]University of Science and Technology, Daejeon, Republic of Korea

[6 ]Korea Institute of Oriental Medicine, Daejeon, Republic of Korea

Author notes

[*]Hyuno Kang, Division of Analytical Science, Korea Basic Science Institute, 169-148, Gwahak-ro, Yuseong-gu, Daejeon 34133, Republic of Korea. Email: hyunokang@ 123456kbsi.re.kr

[*]Hwa Seung Yoo, East West Cancer Center, Seoul Korean Medicine Hospital of Daejeon University, Seoul 05836, Rep. of Korea. Email: altyhs@ 123456dju.kr

[a]

These authors contributed equally to this work.

Article

Publisher ID: 10.1177_15347354211006191

DOI: 10.1177/15347354211006191

PMC ID: 8077490

PubMed ID: 33884928

SO-VID: 95694f35-a010-472c-aa98-8336ae2f8099

License:

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 9 March 2021

Date revision received : 9 March 2021

Date accepted : 10 March 2021

Funding

Funded by: Korea Institute of Oriental Medicine, FundRef https://doi.org/10.13039/501100003718;

Award ID: PB2020097

Funded by: Korea Basic Science Institute, FundRef https://doi.org/10.13039/501100003716;

Award ID: C39121

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cover-date January-December 2021

typesetter ts1

Keywords: chelidonine,pancreatic cancer,apoptosis,p53,gadd45a

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Keywords: chelidonine, pancreatic cancer, apoptosis, p53, gadd45a

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Chelidonine Induces Apoptosis via GADD45a-p53 Regulation in Human Pancreatic Cancer Cells

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Karger: Oncology

Most cited references 55

TopHat: discovering splice junctions with RNA-Seq

Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors

Improving RNA-Seq expression estimates by correcting for fragment bias

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