title: Increased aqueous solubility and proapoptotic activity of potassium koetjapate against human colorectal cancer cells.
abstract: OBJECTIVE
  Recently, we have isolated koetjapic acid (KA) from Sandoricum koetjape and identified its selective anticancer potentiality against colorectal carcinoma. KA is quite likely to be useful as a systemic anticancer agent against colorectal malignancy. However, with extremely low solubility, KA has to be converted into a biocompatible solubilized form without compromising the bioefficacy. Objective of this study is to enhance solubility of KA and to evaluate anticancer efficacy of potassium koetjapate in human colorectal cancer cells.
  
  
  METHODS
  (2-Hydroxypropyl)-β-cyclodextrin inclusion complex and solid dispersions (carboxymethyl cellulose, polyvinylpyrrolidone and sodium lauryl sulphate) of KA were prepared. In addition, a salt of KA, potassium koetjapate was synthesized.
  
  
  RESULTS
  Potassium koetjapate demonstrated higher solubility than the other tested formulations with enhanced cytotoxicity against HCT 116 cells. The enhanced efficacy of potassium koetjapate is attributed to apoptotic induction of nuclear condensation and disruption of mitochondrial membrane potential in the cells. Interestingly, potassium koetjapate was found to be safe in rats after oral administration (LD50  > 2000 mg/kg).
  
  
  CONCLUSIONS
  The salt formulation of KA appears to modulate the capability of the parent compound by enhancing its solubility and improves its bioefficacy against colon cancer cells, suggesting attractive roles for its applications in medicine.
authors.affiliation: EMAN Research and Testing Laboratory, Universiti Sains Malaysia, Minden, Pulau Pinang, Malaysia.
authors.forename: Seyedeh Fatemeh
authors.initials: SF
authors.lastname: Jafari
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Khadeer Ahamed
authors.forename: Muhammad Adnan
authors.initials: MA
authors.lastname: Iqbal
authors.forename: Fouad Saleih R
authors.initials: FS
authors.lastname: Al Suede
authors.forename: Syed Haroon
authors.initials: SH
authors.lastname: Khalid
authors.forename: Rosenani A
authors.initials: RA
authors.lastname: Haque
authors.forename: Zeyad D
authors.initials: ZD
authors.lastname: Nassar
authors.forename: Muhammad Ihtisham
authors.initials: MI
authors.lastname: Umar
authors.forename: Amin Malik Shah
authors.initials: AM
authors.lastname: Abdul Majid
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D045325:HCT116 Cells; D006801:Humans; D029582:Meliaceae / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011188:Potassium / Q000737:chemistry*; D012995:Solubility; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014867:Water / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D014315:Triterpenes; C573794:koetjapic acid; D014867:Water; D011188:Potassium
keywords: Sandoricum koetjape; colorectal cancer; koetjapic acid; potassium koetjapate; proapoptosis