Triphenylmethyl derivatives enhances the anticancer effect of immunotoxins

Karianne Risberg, Ingrid Jenny Guldvik, Rahul Palchaudhuri, Yaguang Xi, Jingfang Ju, Øystein Fodstad, Paul J. Hergenrother, Yvonne Andersson

Research output: Contribution to journalArticlepeer-review


The combined use of several drugs targeting different cellular functions is one approach to achieve tumor control in cancer. We studied the effects of Pseudomonas exotoxin A (PE)-based immunotoxins (ITs), the 9.2.27PE and the 425.3PE, together with 2 different triphenylmethyl derivatives, triphenylmethyl phosphonates and phosphonochloridates (TPMP)-I-2 and 4BI. Combining the triphenylmethyl derivatives with ITs enhanced the cytotoxic effect of the ITs, with TPMP-I-2 in combination with the 425.3PE (targeting the epidermal growth factor receptor) being the most promising combination. The cytotoxicity involving signs of apoptosis was observed in cancer cells from different origins in vitro. It is interesting to note that treatment with IT, TPMP-I-2, or 4BI alone or in combination resulted in strongly decreased protein levels of stearoyl-CoA desaturase. Stearoyl-CoA desaturase is the rate-limiting enzyme for converting saturated fatty acids into monounsaturated fatty acids needed for membrane genesis. Furthermore, the combination of 425.3PE and TPMP-I-2 prolonged the survival time of nude rats in a simulated micrometastatic cervical cancer model. In addition, we demonstrate that a combination of the 425.3PE and 4BI was more effective in reducing tumor growth in a breast cancer model in nude mice compared with either agent alone.

Original languageEnglish (US)
Pages (from-to)438-447
Number of pages10
JournalJournal of Immunotherapy
Issue number5
StatePublished - Jun 2011


  • apoptosis
  • immunotoxin
  • protein synthesis
  • stearoyl-CoA desaturase
  • triphenylmethyl derivatives

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research


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