A novel protein fraction from Sesbania grandiflora shows potential anticancer and chemopreventive efficacy, in vitro and in vivo.
We report mechanism-based evidence for the anticancer efficacy of a protein fraction, SF2 (Sesbania fraction 2) isolated from the flower of the medicinal plant, Sesbania grandiflora (S. grandiflora). The fraction was evaluated in two murine ascites tumour cell lines and human cancer cell lines of different origin for its anticancer effect. SF2 inhibited cell proliferation and induced apoptosis as demonstrated by DNA fragmentation and externalization of phosphatidyl serine in Daltons lymphoma ascites (DLA) and colon cancer cells (SW-480). Sensitivity to SF2 in these cells was associated with activation of caspases 3, 8 and 9, poly (ADP-ribose) polymerase cleavage and cytochrome C release which attests apoptosis induced cell death. Mechanistically, SF2 down-regulated phorbol myristate acetate (PMA) induced NF-kappaB, a transcription factor which controls the expression of genes encoding proteins involved in cell regulation and growth control. Additionally, SF2 also down-regulated anti-apoptotic factors such as Bcl-2, p-Akt and cyclooxygenase-2 induced by the tumour promoter PMA suggestive of a possible explanation for its anticancer effect. In vivo studies using ascites and solid tumour models strongly support in vitro findings as SF2 administration increased the life span and decreased the tumour volume in mice bearing tumour. In vivo toxicological evaluation revealed the pharmacological safety of SF2 and may serve as a potential anticancer drug candidate.
Laladhas
Krishna P
KP
Department of Zoology, St. Stephan's College, Pathanapuram, Kerala, India.
Cheriyan
Vino T
VT
Puliappadamba
Vineshkumar T
VT
Bava
Smitha V
SV
Unnithan
Rajesh G
RG
Vijayammal
Parvathy L
PL
Anto
Ruby John
RJ
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D035264:Flowers / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D010940:Plant Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D049931:Sesbania / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016328:NF-kappa B; D010936:Plant Extracts; D010940:Plant Proteins; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D013755:Tetradecanoylphorbol Acetate