title: Corchorusin-D directed apoptosis of K562 cells occurs through activation of mitochondrial and death receptor pathways and suppression of AKT/PKB pathway.
abstract: Saponins, plant glycosides, have been reported to possess anti-cancer properties. Therefore the effect of corchorusin-D (COR-D), a compound isolated from Corchorus acutangulus, was studied in the chronic myelogenous leukemic cell line K562, using MTT assay, phase contrast and confocal microscopy, annexin V binding, cell cycle analysis and western blotting. COR-D inhibited cell growth in K562 cells and showed increased number of Annexin V FITC binding cells. Characteristic apoptotic changes, seen under phase contrast and confocal microscopes with accumulation of cells in the sub-G0 phase. The apoptosis involved drop in Bcl-2/Bax ratio, loss of mitochondrial membrane potential, release of cytochrome c in cytosol followed by activation of caspases 9 and 3, and cleavage of PARP. Down-regulation of pro-caspase 10 was observed along with formation of death-inducing signaling complex between TNF-R1 and TRADD. COR-D suppressed PDK1 and AKT with activation of MAP kinase family members ERK1/2, JNK1/2 and p38. Thus it induced apoptosis by activating mitochondrial and death receptor pathways and suppressing AKT/PKB rather than MAP kinase pathway. Significant enhancement of apoptosis, noted using specific inhibitors of ERK1/2, p38 and JNK1/2, suggests that COR-D can enhance apoptosis in K562 cells in combination with MAP kinase inhibitors.
authors.affiliation: Cancer and Cell Biology Division, CSIR Indian Institute of Chemical Biology, 4, Raja, S.C.Mullick Road, Jadavpur, Kolkata-700032, India.
authors.forename: Sumana
authors.initials: S
authors.lastname: Mallick
authors.forename: Bikas C
authors.initials: BC
authors.lastname: Pal
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Vedasiromoni
authors.forename: Deepak
authors.initials: D
authors.lastname: Kumar
authors.forename: Krishna D
authors.initials: KD
authors.lastname: Saha
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D032381:Corchorus / Q000737:chemistry; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006027:Glycosides; D019253:Proto-Oncogene Proteins c-bcl-2; D053218:Receptors, Death Domain; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C067483:corchorusin D; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9