Methyl angolensate, a natural tetranortriterpenoid induces intrinsic apoptotic pathway in leukemic cells

Chiruvella, Kishore K.; Kari, Vijayalakshmi; Choudhary, Bibha; Nambiar, Mridula; Ghanta, Rama Gopal; Raghavan, Sathees C.

doi:10.1016/j.febslet.2008.11.001

« Previous Next »FEBS Letters
Volume 582, Issue 29 , Pages 4066-4076, 10 December 2008

Methyl angolensate, a natural tetranortriterpenoid induces intrinsic apoptotic pathway in leukemic cells

Edited by Varda Rotter

Kishore K. Chiruvella
- Department of Biochemistry, Indian Institute of Science, Malleswaram, Bangalore 560 012, Karnataka, India
Vijayalakshmi Kari
- Department of Biochemistry, Indian Institute of Science, Malleswaram, Bangalore 560 012, Karnataka, India
Bibha Choudhary
- Manipal Institute of Regenerative Medicine, Manipal University, Bangalore 560 071, Karnataka, India
Mridula Nambiar
- Department of Biochemistry, Indian Institute of Science, Malleswaram, Bangalore 560 012, Karnataka, India
Rama Gopal Ghanta
- Division of Plant Tissue Culture, Sri Venkateswara University, Tirupati, AP, India
Sathees C. Raghavan
- Department of Biochemistry, Indian Institute of Science, Malleswaram, Bangalore 560 012, Karnataka, India
- Corresponding author. Tel.: +9180 2293 2674; fax: +91 80 2360 0814.

Received 6 September 2008; received in revised form 1 November 2008; accepted 4 November 2008. published online 18 November 2008.

Abstract

Methyl angolensate (MA), a natural tetranortriterpenoid, purified from Soymida febrifuga is examined for the first time for its anticancer properties. We find that MA inhibits growth of T-cell leukemia and chronic myelogenous leukemia cells in a time- and dose-dependent manner. Accumulation of cells in the subG1 peak, annexin V binding and DNA fragmentation suggested induction of apoptosis. Besides, upregulation of BAD (proapoptotic) and downregulation of BCL2 (antiapoptotic) gene products further supported induction of apoptosis. Loss of mitochondrial membrane potential, activation of caspase 9, caspase 3, cleavage of PARP, downregulation of Ku70/80 and phosphorylation of MAP kinases suggested that MA could induce intrinsic pathway of apoptosis in leukemic cells.

Keywords: Cytotoxicity, Double-strand break, Cancer therapeutics, Chemotherapy, Callus, DNA damage