Increased aqueous solubility and proapoptotic activity of potassium koetjapate against human colorectal cancer cells

Seyedeh Fatemeh Jafari, Mohamed B. Khadeer Ahamed, Muhammad Adnan Iqbal, Fouad Saleih R. Al Suede, Syed Haroon Khalid, Rosenani A. Haque, Zeyad D. Nassar, Muhammad Ihtisham Umar, Amin Malik Shah Abdul Majid

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Objectives 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. Key findings 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.

Original languageEnglish
Pages (from-to)1394-1409
Number of pages16
JournalJournal of Pharmacy and Pharmacology
Volume66
Issue number10
DOIs
Publication statusPublished - 1 Oct 2014

Keywords

  • Sandoricum koetjape
  • colorectal cancer
  • koetjapic acid
  • potassium koetjapate
  • proapoptosis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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