Shattering the underpinnings of neoplastic architecture in LNCap: synergistic potential of nutraceuticals in dampening PDGFR/EGFR signaling and cellular proliferation

J Exp Ther Oncol. 2011;9(3):201-6.

Abstract

Objective: Prostate cancer is a polyfactorial molecular anomaly that is offering refractoriness against a broad range of therapeutic drugs. Growth factor receptors are actively implicated in oncogenesis. PDGFR/EGFR mediated exacerbated signaling has a central participation and is contributory in fueling the signal transductions that gear up prostate cancer progression.

Materials and methods: In this particular study, androgen sensitive, Prostate cancer cell line (LNCaP) was used. Pretreatment of cell line with PDGF resulted in an enhanced proliferation of cells which was evaluated by MTT assay. Treatment of cell line with either alone Curcumin, EGCG, sulforaphane or in combination was evaluated. PDGFR/EGFR activation (phosphorylation) was studied using western blot.

Results: Results indicated that phosphorylation was gradually downregulated after treatment with individual compound. However there was a remarkable decrease in cellular proliferation after a combinatorial approach which is indicative of the fact that PDGFR phosphorylation was decreased outstandingly as evaluated by MTT assay. That also gave a prominent decline in the expression and subsequent decrease in proliferation pattern of cells.

Conclusion: Despite the fact that little is still known regarding the mechanistic insights by which phytonutrients act as barrier to cancer, and attempts to translate the studies from benchtop to bedside are in progress. A detailed analysis of nutraceuticals will help a lot in identifying the stumbling blocks in the standardization of therapeutic interventions.

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Catechin / analogs & derivatives
  • Catechin / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Curcumin / pharmacology
  • Drug Synergism
  • ErbB Receptors / drug effects
  • ErbB Receptors / metabolism*
  • Humans
  • Isothiocyanates
  • Male
  • Phosphorylation / drug effects
  • Prostatic Neoplasms / metabolism*
  • Receptor, Platelet-Derived Growth Factor beta / drug effects
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Signal Transduction / drug effects*
  • Thiocyanates / pharmacology

Substances

  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • Isothiocyanates
  • Thiocyanates
  • Catechin
  • epigallocatechin gallate
  • ErbB Receptors
  • Receptor, Platelet-Derived Growth Factor beta
  • sulforafan
  • Curcumin