Sanguinarine induces apoptosis of human pancreatic carcinoma AsPC-1 and BxPC-3 cells via modulations in Bcl-2 family proteins

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Sanguinarine induces apoptosis of human pancreatic carcinoma AsPC-1 and BxPC-3 cells via modulations in Bcl-2 family proteins

Haseeb Ahsan1, Shannon Reagan-Shaw1, Jorien Breur, Nihal Ahmad Corresponding Author Contact Information, E-mail The Corresponding Author

Department of Dermatology, University of Wisconsin, Medical Science Center, 1300 University Avenue, Madison, Wisconsin 53706, USA

Received 31 July 2006; revised 15 August 2006; Accepted 17 August 2006. Available online 26 September 2006.

Abstract

Pancreatic cancer is associated with low responsiveness to conventional chemotherapies and its incidence nearly equals its death rate. This warrants the development of novel mechanism-based approaches for the management of pancreatic cancer. This study was designed to determine the potential of sanguinarine, a plant alkaloid known to possess strong antimicrobial, anti-inflammatory, and antioxidant activities, against human pancreatic carcinoma cells. Employing human pancreatic carcinoma AsPC-1 and BxPC-3 cells, we specifically evaluated the pro-apoptotic and cell cycle deregulatory effects of sanguinarine and evaluated the involvement of Bcl-2 family proteins and p53 as the mechanism of the biological effects of sanguinarine. Our data demonstrated that sanguinarine (at low concentrations of 0.1–10 ?M; for 24 h) treatment to AsPC-1 and BxPC-3 cells resulted in a dose dependent (i) inhibition of viability and growth, (ii) colony formation ability, (iii) induction of apoptosis, and (iv) G0-G1 phase cell cycle arrest. Further, sanguinarine-treatment to AsPC-1 and BxPC-3 cells resulted in a dose dependent (i) increase in pro-apoptotic Bax, Bid and Bak proteins; (ii) decrease in anti-apoptotic Bcl-2 and Bcl-XL proteins; and (iii) decrease in p53 with an increase in its phosphorylation. Based on our study, we suggest that sanguinarine may be developed as an agent for the management of pancreatic cancer. Indeed, more in depth studies both in vitro as well as in vivo in appropriate relevant animal models are needed to strengthen this suggestion.

Keywords: Sanguinarine; Pancreatic cancer; Apoptosis; Cell cycle; Bcl-2 family proteins