Silibinin exerts sustained growth suppressive effect against human colon carcinoma SW480 xenograft by targeting multiple signaling molecules.
OBJECTIVE
Earlier, we reported the strong preventive efficacy of silibinin against colorectal cancer (CRC), but its usefulness against established CRC or effect of its withdrawal on CRC growth remained unknown. Present study focused on these important issues by employing two different treatment protocols in advanced human CRC SW480 xenograft in nude mice.


METHODS
In the first treatment protocol, silibinin was fed for 28 days (200 mg/kg body weight, 5 days/week) to mice with growing SW480 xenograft; thereafter, tumor growth was monitored for additional 3 weeks without silibinin treatment. In the second protocol, silibinin treatment was started after 25 days of SW480 cells injection (established tumors), and tumor growth was studied 4 days, 8 days and 16 days after silibinin treatment.


RESULTS
In both treatment protocols, silibinin had strong and sustained inhibitory effect on xenograft growth. Detailed xenograft analyses showed that silibinin, in both treatment protocols, exerts anti-proliferative, pro-apoptotic and anti-angiogenic effects. Further, silibinin reduced the expression of β-catenin and phospho-GSK3β in xenograft tissues. Silibinin also targeted signaling molecules involved in CRC proliferation and survival (cyclin D1, c-Myc and survivin) as well as angiogenesis regulators (VEGF and iNOS).


CONCLUSIONS
Collectively, these findings substantiate silibinin's therapeutic efficacy against CRC, advocating its translational potential.
Velmurugan
Balaiya
B
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, Colorado 80045, USA.
Gangar
Subhash Chander
SC
Kaur
Manjinder
M
Tyagi
Alpna
A
Deep
Gagan
G
Agarwal
Rajesh
R
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D036341:Intercellular Signaling Peptides and Proteins; D012838:Silymarin; D000077385:Silybin