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      Novel synthetic oleanane triterpenoid AMR-MeOAc inhibits K-Ras through ERK, Akt and survivin in pancreatic cancer cells.

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          Abstract

          K-Ras activating mutations are a major problem that drives aggressive tumor growth and metastasis in pancreatic cancer. Currently, there are no effective targeted therapies for this genetically defined subset of cancers harboring oncogenic K-Ras mutations that confer drug resistance, aggressive tumor growth, metastasis and poor clinical outcome. We identified a novel synthetic oleanane triterpenoid compound designated AMR-MeOAc that effectively kills K-Ras mutant pancreatic cancer HPAF-II cells. The cytotoxic effects correlated with apoptosis induction, as was evidenced by increase of apoptosis cells upon the treatment of AMR-MeOAc in HPAF-II cells. Our studies revealed that AMR-MeOAc treatment inhibits cancer associated survival gene survivin. Moreover, AMR-MeOAc also led to down regulation of Akt, ERK1/2 and survivin protein levels. Our results indicate that AMR-MeOAc or its active analogs could be a novel class of anticancer agents against K-Ras driven human pancreatic cancer.

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          Author and article information

          Journal
          Phytomedicine
          Phytomedicine : international journal of phytotherapy and phytopharmacology
          Elsevier BV
          1618-095X
          0944-7113
          Mar 15 2014
          : 21
          : 4
          Affiliations
          [1 ] Siddha Clinic and Research Center SVA, Kanyakumari, India. Electronic address: thangaiyanrabi@hotmail.com.
          [2 ] Captain Srinivasamurthy Drug Research Institute for Ayurveda, Chennai, India.
          Article
          S0944-7113(13)00404-2
          10.1016/j.phymed.2013.09.017
          24215674
          f1c956cc-5513-4c6a-932c-8eb0153a49a0
          History

          ERK1/2 and Akt1,Survivin,K-Ras activating mutations,Pancreatic cancer,AMR-MeOAc,Apoptosis

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