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Cited by 116Phytochemicals and Medicinal PlantsPancreatic and Hepatic Oncology ResearchPharmacological Effects of Medicinal Plants

The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.

Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells

Li, Xu, Zhu, Feng, Jiang, Jianxin, Sun, Chengyi, Wang, Xin, Shen, Ming, Tian, Rui, Shi, Chengjian, Xu, Meng, Peng, Feng, Guo, Xingjun, Wang, Min, Qin, Renyi·2015·Cancer Letters
DOI 10.1016/j.canlet.2014.11.026
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Abstract

Application of oxaliplatin for the treatment of pancreatic cancer (PC) is restricted owing to its toxic side effects and drug resistance. We investigated how withaferin A (WA), a bioactive component isolated from the medicinal plant Withania somnifera, acts synergistically with oxaliplatin on human PC in vitro and in vivo. We found that WA enhanced oxaliplatin-induced growth suppression and apoptosis in PC cells dramatically through a mechanism involving mitochondrial dysfunction and inactivation of the PI3K/AKT pathway. Combination treatment resulted in significant accumulation of intracellular reactive oxygen species (ROS). Pretreatment of cells with the ROS scavenger N-acetylcysteine completely blocked the apoptosis induced by combination treatment, and recovered expression of AKT inactivation, which revealed the important role of ROS in apoptosis and AKT regulation. In vivo, combination therapy showed the strongest anti-tumor effects compared with single agents, without obvious additional toxicity. These results support the notion that combination treatment with oxaliplatin and WA could facilitate development of an effective strategy for PC treatment.

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Metadata

Authors
Li, X., Zhu, F., Jiang, J., Sun, C., Wang, X., Shen, M., Tian, R., Shi, C., Xu, M., Peng, F., Guo, X., Wang, M., & Qin, R.
Affiliations
  • Tongji Hospital (CN)
  • Guiyang Medical University (CN)
Corresponding author
  • Wang, Min
  • Qin, Renyi
ORCID
Venue
Cancer Letters
Publisher
Elsevier BV
Published
2015-02
Volume
357
Issue
1
Pages
219-230
ISSN
0304-3835 (ISSN-L)
DOI
10.1016/j.canlet.2014.11.026
OpenAlex
W2032234787
Cited by
116
References
51
Citations by year
2026: 5 · 2025: 2 · 2024: 14 · 2023: 10 · 2022: 9 · 2021: 11 · 2020: 19 · 2019: 11 · 2018: 6 · 2017: 14 · 2016: 8 · 2015: 7
FWCI
20.69
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Cancer Letters (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81272659, 81101621, 81160311, 81372353, 81172064, 81301860)
  • National “Eleventh Five-Year” Scientific and Technological Support Projects (2006BAI02A13-402)
  • Projects of Science Foundation of Hubei Province (2012FFB02401)
  • International S&T Cooperation Projects of China (2014DFA31420)
  • Research Fund of Young Scholars for the Doctoral Program of Higher Education of China (20110142120014)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Pharmacology (medical) › Pharmacological Effects of Medicinal Plants
Keywords
withaferin A, oxaliplatin, pancreatic cancer, combination chemotherapy, synergistic antitumor effect, reactive oxygen species, PI3K/Akt signaling, apoptosis, mitochondrial dysfunction, N-acetylcysteine, drug resistance, Withania somnifera
MeSH terms
Oxaliplatin, Animals, Antineoplastic Combined Chemotherapy Protocols, Drug Synergism, Humans, Male, Mice, Inbred BALB C, Mice, Nude, Organoplatinum Compounds, Pancreatic Neoplasms, Prognosis, Random Allocation, Signal Transduction, Apoptosis, Reactive Oxygen Species, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Mice, Withanolides

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