Methylseleninic acid suppresses pancreatic cancer growth involving multiple pathways

Lei Wang, Hongbo Hu, Zhe Wang, Hua Xiong, Yan Cheng, Dezhong J Liao, Yibin Deng, Junxuan Lü

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

As a potential novel agent for treating pancreatic cancer, methylseleninic acid (MSeA) was evaluated in cell culture and xenograft models. Results showed that MSeA induced G1 cell cycle arrest and apoptosis in a majority of human and mouse pancreatic cancer cell lines, but G2 arrest in human PANC-1 and PANC-28 cell lines. In contrast to our previous finding in human prostate cancer LNCaP cells having a lack of P53 activation by MSeA, induction of G2 arrest in PANC-1 cells was accompanied by increased mutant P53 Ser15 phosphorylation, upregulation of P53-targets P21Cip1 and GADD45 and G 2 checkpoint kinase (Chk2) activation, suggestive of DNA damage responses. A rapid inhibition of AKT phosphorylation was followed by reduced mTOR signaling and increased autophagy in PANC-1 cells attenuating caspase-mediated apoptosis execution. Furthermore, daily oral treatment with MSeA (3 mg Se/kg body weight) significantly suppressed growth of subcutaneously inoculated PANC-1 xenograft in SCID mice. Immunohistochemical analyses detected increased p-Ser15 P53, P21Cip1, pS139-H2AX (DNA damage responses), and caspase-3 cleavage and decreased pSer473AKT and Ki67 proliferative index and reduced intratumor vascular density in MSeA-treated xenograft. These results provide impetus for further research of MSeA in the therapy and/or chemoprevention of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)295-307
Number of pages13
JournalNutrition and Cancer
Volume66
Issue number2
DOIs
StatePublished - Feb 1 2014

Bibliographical note

Funding Information:
This article was supported by grants from the National Cancer Institute R01CA126880 (to Junxuan Lü) and R21CA155522 (to Yibin Deng and Junxuan Lü).

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