title: Anti-cancer effects of novel flavonoid vicenin-2 as a single agent and in synergistic combination with docetaxel in prostate cancer.
abstract: The present study was conducted to determine the efficacy of novel flavonoid vicenin-2 (VCN-2), an active constituent of the medicinal herb Ocimum Sanctum Linn or Tulsi, as a single agent and in combination with docetaxel (DTL) in carcinoma of prostate (CaP). VCN-2 effectively induced anti-proliferative, anti-angiogenic and pro-apoptotic effect in CaP cells (PC-3, DU-145 and LNCaP) irrespective of their androgen responsiveness or p53 status. VCN-2 inhibited EGFR/Akt/mTOR/p70S6K pathway along with decreasing c-Myc, cyclin D1, cyclin B1, CDK4, PCNA and hTERT in vitro. VCN-2 reached a level of 2.6±0.3μmol/l in serum after oral administration in mice which reflected that VCN-2 is orally absorbed. The i.v. administration of docetaxel (DTL), current drug of choice in androgen-independent CaP, is associated with dose-limiting toxicities like febrile neutropenia which has lead to characterization of alternate routes of administration and potential combinatorial regimens. In this regard, VCN-2 in combination with DTL synergistically inhibited the growth of prostate tumors in vivo with a greater decrease in the levels of AR, pIGF1R, pAkt, PCNA, cyclin D1, Ki67, CD31, and increase in E-cadherin. VCN-2 has been investigated for radioprotection and anti-inflammatory properties. This is the first study on the anti-cancer effects of VCN-2. In conclusion, our investigations collectively provide strong evidence that VCN-2 is effective against CaP progression along with indicating that VCN-2 and DTL co-administration is more effective than either of the single agents in androgen-independent prostate cancer.
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope, National Medical Center, Duarte, CA 91010, USA.
authors.forename: Lokesh Dalasanur
authors.initials: LD
authors.lastname: Nagaprashantha
authors.forename: Rit
authors.initials: R
authors.lastname: Vatsyayan
authors.forename: Jyotsana
authors.initials: J
authors.lastname: Singhal
authors.forename: Spence
authors.initials: S
authors.lastname: Fast
authors.forename: Rhonda
authors.initials: R
authors.lastname: Roby
authors.forename: Sanjay
authors.initials: S
authors.lastname: Awasthi
authors.forename: Sharad S
authors.initials: SS
authors.lastname: Singhal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects; D047310:Apigenin / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D000077143:Docetaxel; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005960:Glucosides / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D000970:Antineoplastic Agents; D005960:Glucosides; D043823:Taxoids; C530449:apigenin-6,8-di-C-glycopyranoside; D000077143:Docetaxel; D047310:Apigenin