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Pharmacological targets and molecular mechanisms of plumbagin to treat colorectal cancer: A systematic pharmacology study.

Abstract
Plumbagin (PL) pharmacologically plays the anti-proliferative effects in cancer cells, including effective suppression of colorectal cancer (CRC). However, the exact molecular mechanism of PL to treat CRC remains unclear. Using available SwissTargetPrediction and SuperPred databases, the anti-cancer biotargets of PL were identified, and the CRC-diseased targets were obtained through a DisGeNET database. The biological processes, and signaling pathways of PL to treat CRC were identified and visualized. Further, clinical and cell culture data were used to validate some bioinformatic findings. As shown in bioinformatics findings, 64 predictive biotargets of PL to treat CRC were collected, and 7 most important biotargets of tumor protein p53 (TP53), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), mitogen-activated protein kinase 1 (MAPK1), E1A-associated protein p300 (EP300), poly (ADP-ribose) polymerase 1 (PARP1), nuclear factor kappa p65 protein (RELA), Bcl-2 like protein 1 (BCL2L1) were identified respectively. In addition, top 20 functional biological processes, signaling pathways of PL to treat CRC were screened and prioritized. In human study, CRC samples showed elevated expressions of neoplastic MAPK1, PARP1 mRNAs and reduced EP300 mRNA level. In cell culture study, PL-treated CRC cells resulted in down-regulated MAPK1, PARP1 mRNA expressions and up-regulation of EP300 mRNA level, characterized with suppressed cell proliferation. Taken together, the therapeutic biotargets and molecular mechanisms of PL to treat CRC were screened and identified by using a systematic pharmacology analysis, and some bioinformatic findings were validated in clinical and cell line experiments. Potentially, these hub biotargets may be the biomarkers for CRC detection and treatment.
AuthorsYujia Liang, Rui Zhou, Xiaoliu Liang, Xiaolong Kong, Bin Yang
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 881 Pg. 173227 (Aug 15 2020) ISSN: 1879-0712 [Electronic] Netherlands
PMID32505664 (Publication Type: Journal Article)
CopyrightCopyright © 2020 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Naphthoquinones
  • plumbagin
Topics
  • Aged
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Cell Proliferation (drug effects)
  • Colorectal Neoplasms (drug therapy, genetics, metabolism, pathology)
  • Databases, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • HCT116 Cells
  • Humans
  • Male
  • Middle Aged
  • Naphthoquinones (pharmacology)
  • Protein Interaction Maps
  • Signal Transduction
  • Systems Biology
  • Transcriptome

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