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Tumour Biol. 2016 Sep;37(9):12455-12464. Epub 2016 Jun 22.

Aphanin, a triterpenoid from Amoora rohituka inhibits K-Ras mutant activity and STAT3 in pancreatic carcinoma cells.

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Siddha Clinic and Research Center SVA, Kanyakumari, Tamil Nadu, India.
Tumor Biology and Experimental Therapeutics Program, Institute of Oncology Research (IOR), Bellinzona, Switzerland.
Tumor Biology and Experimental Therapeutics Program, Institute of Oncology Research (IOR), Bellinzona, Switzerland.
Department of Oncology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.


Mutations of the K-Ras gene occur in over 90 % of pancreatic carcinomas, and to date, no targeted therapies exist for this genetically defined subset of cancers. STAT3 plays a critical role in KRAS-driven pancreatic tumorigenesis, suggesting its potential as a therapeutic target in this cancer. Therefore, finding novel and potential drugs to inhibit oncogenic K-Ras is a major challenge in cancer therapy. In an attempt to develop novel anti-KRAS mutant chemotherapeutics, we isolated three novel triterpenoids from Amoora rohituka stem and their chemical structures were characterized by extensive 1H-NMR, 13C-NMR, Mass, IR spectroscopic studies and chemical transformations. Aphanin (3 alpha-angeloyloxyolean-12-en-28-oic acid) is one of the isolated novel triterpenoid compounds. We found aphanin exhibited antiproliferative effects, caused G0-G1 cell cycle arrest, inhibits K-Ras G12D mutant activity by decreased STAT3, p-STAT3, Akt, p-Akt, cyclin D1 and c-Myc expressions, and induced apoptosis in pancreatic cancer HPAF-II (ΔKRAS G12D ) cells. The apoptosis proceeded through depletion of GSH with a concomitant increase in the reactive oxygen species production. The results of our study have important implications for the development of aphanin as potential novel agent for the treatment of K-Ras mutant pancreatic cancer, and STAT3-cMyc-cyclinD1 axis may serve as an important predictive biomarker for the therapeutic efficacy.


Aphanin; Apoptosis; Oncogenic K-Ras; Pancreatic cancer; ROS; STAT3

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