Abstract

Maslinic acid (MA) is a triterpenoid compound of natural abundance in olive plants possessing numerous biological activities. The effect and molecular mechanism of MA on pancreatic cancer cells remain elusive. Here, we explored the anti-tumor activity of MA on human pancreatic cancer cells and the potential underlying molecular mechanism. The anti-cancer effects of MA on whole-cell processes, including proliferation, migration, and invasion in pancreatic cancer cells, were systematically assessed by colony formation, transwell, and migration assays. The search for potential therapeutic targets was achieved via transcriptomics and proteomics analyses. MA was demonstrated to inhibit the proliferation, migration, and invasion of PANC-1 and Patu-8988 cells, but induced apoptosis of these cells. Several key candidate genes and proteins of functional relevance for the anti-tumor activity of MA were identified through the association analysis of transcriptomics and proteomics. To our knowledge, this is the first transcription and proteomics-based comprehensive analysis of the mechanism of MA against pancreatic cancer. The findings demonstrate that MA holds promise as a therapeutic drug for managing pancreatic cancer.

Highlights

  • Pancreatic cancer is a highly lethal malignancy with a poor prognosis due to its high propensity for local invasion and early metastasis [1]

  • The effects of Maslinic acid (MA) on the proliferation of PANC-1 and Patu-8988 cells were evaluated through unlabeled RealTime Cell Analysis (RTCA), Ki67 immunofluorescence, and colony formation assay

  • Results demonstrated markedly higher levels of UACA or Adenylate kinase 4 (AK4) in cells transfected with pcDNA3.1(+)-UACAFlag or pcDNA3.1(+)-AK4-Flag compared to cells transfected with control pcDNA3.1(+)

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Summary

Introduction

Pancreatic cancer is a highly lethal malignancy with a poor prognosis due to its high propensity for local invasion and early metastasis [1]. Gemcitabine and 5fluorouracil, first-line chemotherapeutic agents, have been widely adopted to manage pancreatic cancer; drug resistance of cancer cells greatly limits their efficacy [3]. New anti-cancer drugs are needed urgently to improve the therapeutic effects and survival of pancreatic cancer patients. MA has potent significant inhibitory effects on the expression of B cell lymphoma 2 (Bcl-2) and elevate the expression of Bcl2-associated X protein (Bax) to activate mitochondrial apoptosis pathway in colon cancer cells [13]. In this www.aging-us.com view, MA is hypothesized to have potential inhibitory effect on pancreatic cancer cells

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