Suppression of tumor growth and invasion in 9,10 dimethyl benz(a) anthracene induced mammary carcinoma by the plant bioflavonoid quercetin.
Administration of quercetin, a common polyphenolic component of many vascular and edible plants including vegetables, fruits and tea significantly reduced the tumor volume in rats induced for mammary carcinoma using dimethyl benz (a) anthracene (DMBA). Dose response was assessed, by treating the animals with different doses (15-45 mg/kgbw) of quercetin and 25 mg/kgbw was taken as effective dose. Quercetin was administered as an intra tumoral injection once a week for 4 weeks. Serum levels of carcino embryonic antigen (CEA), a potent marker for tumor growth and invasion was significantly decreased on quercetin treatment. Quercetin caused a significant decrease in the activities of acid phosphatase and Cathepsin D in serum of experimental animals. Activities of lysosomal enzymes- (beta-D galactosidase, beta-D glucuronidase, beta-D glucosidase and sialidase), in serum and tissue were significantly altered in DMBA animals compared to control animals. However, quercetin treatment caused no significant change in lysosomal enzyme activities in tissues, whereas the activities were significantly lowered in serum. Partial purification of tissue type plasminogen activator (t-PA) from the tumor and kidney showed increased activity in the DMBA induced animals. Serum urokinase, -like plasminogen activator (u-PA) was also increased in animals with tumor, indicating tumor invasion. Administration of quercetin caused a significant decrease of both t-PA and u-PA. In conclusion, the present study suggests the possible role of quercetin in primary and invasive mammary tumor treatment. The above observations in vivo warrant further studies, due to the easy availability, common occurrence and low toxicity of this dietary bioflavonoid.
Devipriya
Sankarasharma
S
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India. sdpriya@gmail.com
Ganapathy
Vani
V
Shyamaladevi
Chennam Srinivasulu
CS
D000135:Acid Phosphatase / Q000097:blood; D000818:Animals; D000873:Anthracenes / Q000633:toxicity; D002272:Carcinoembryonic Antigen / Q000097:blood; D002402:Cathepsin D / Q000097:blood; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005966:Glucuronidase / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009439:Neuraminidase / Q000097:blood / Q000378:metabolism; D011794:Quercetin / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood; D001616:beta-Galactosidase / Q000097:blood / Q000378:metabolism; D001617:beta-Glucosidase / Q000097:blood / Q000378:metabolism
D000873:Anthracenes; D002272:Carcinoembryonic Antigen; D011794:Quercetin; C029126:9,10-dimethylanthracene; D000135:Acid Phosphatase; D009439:Neuraminidase; D001617:beta-Glucosidase; D001616:beta-Galactosidase; D005966:Glucuronidase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D002402:Cathepsin D