title: In vitro and in vivo anticancer efficacy of silibinin against human pancreatic cancer BxPC-3 and PANC-1 cells.
abstract: Silibinin suppresses the growth of many cancers; however, its efficacy against pancreatic cancer has not been evaluated in established preclinical models. Here, we investigated in vitro and in vivo effects of silibinin against lower and advanced stages of human pancreatic carcinoma cells. Silibinin (25-100μM) treatment for 24-72h caused a dose- and time-dependent cell growth inhibition of 27-77% (P<0.05-0.001) in BxPC-3 cells, and 22-45% (P<0.01-0.001) in PANC-1 cells. Silibinin showed a strong dose-dependent G1 arrest in BxPC-3 cells (upto 72% versus 45% in control; P<0.001), but a moderate response in advanced PANC-1 cells. Cell death observed in cell growth assay, was accompanied by up to 3-fold increase (P<0.001) in apoptosis in BxPC-3 cells, and showed only slight effect on PANC-1 cells. Dietary feeding of silibinin (0.5%, w/w in AIN-93M diet for 7weeks) inhibited BxPC-3 and PANC-1 tumor xenografts growth in nude mice without any apparent change in body weight gain and diet consumption. Tumor volume and weight were decreased by 47% and 34% (P⩽0.001) in BxPC-3 xenograft, respectively. PANC-1 xenograft showed slower growth kinetics and silibinin decreased tumor volume by 34% (P<0.001) by 7weeks. Another 4weeks of silibinin treatment to PANC-1 xenograft showed 28% and 33% decrease in tumor volume and weight, respectively. Silibinin-fed group of BxPC-3 tumors showed decreased cell proliferation and angiogenesis and an increased apoptosis, however, considerable inhibitory effect was observed only for angiogenesis in PANC-1 tumors. Overall, these findings show both in vitro as well as in vivo anticancer efficacy of silibinin against pancreatic cancer that could involve inhibition of cell proliferation, cell cycle arrest, apoptosis induction and/or decrease in tumor angiogenesis.
authors.affiliation: Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Dhanya
authors.initials: D
authors.lastname: Nambiar
authors.affiliation: Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Vandana
authors.initials: V
authors.lastname: Prajapati
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, CO, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India; School of Life Sciences, Central University of Gujarat, Gandhinagar, India. Electronic address: rana_singh@mail.jnu.ac.in.
authors.forename: Rana P
authors.initials: RP
authors.lastname: Singh
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D006801:Humans; D008297:Male; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000178:diet therapy / Q000188:drug therapy* / Q000473:pathology; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012838:Silymarin; D000077385:Silybin