Captopril, an Angiotensin-Converting Enzyme Inhibitor, Promotes Growth of Immunogenic Tumors in Mice

Abstract

Purpose: Antitumor potential of angiotensin-converting enzyme inhibitors has been shown in different preclinical settings, which always involved immunocompromised organisms or nonimmunogenic tumor models. In our study, we wanted to evaluate the effect of captopril on growth of immunogenic tumors in immunocompetent animals. Experimental Design: We used different murine tumor models to evaluate the effect of captopril on tumor take and survival of tumor-bearing immunocompetent and immunocompromised mice. We used an orthotopic renal cell cancer model and highly immunogenic tumor model, which were based on kidney subcapsular injection of RenCa cells or s.c. injection of MethA cells, respectively. To show the influence of captopril on antigen-specific immune responses, we have used two model antigens (green fluorescent protein and h-galactosidase). Results: Captopril decreased survival of RenCa-bearing, immunocompetent mice in a dosedependent manner and in adjuvant setting. In nephrectomized mice, captopril shortened their survival. Captopril promoted formation of immunogenic MethA sarcoma tumors but had no effect on nonimmunogenic melanoma cells (B78-H1). Treatment of immunocompromised mice bearing MethA tumors or RenCa kidney tumors with captopril did not affect tumor formation nor survival, respectively. Captopril-treated mice immunized with AdLacZ or AdGFP vectors did not generate or generated decreased numbers of antigen-specific CD8 + T cells, respectively. However, they showed B-cell responses represented by infiltration of MethA tumors with activated B cells and dramatically increased serum level of h-galactosidase-specific antibodies. Conclusions: Our results show a novel role of captopril in tumor biology and the tumor-promoting properties of captopril seem to be associated with its immunomodulatory potential.

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

“…However, a few reports have suggested that ACEis may actually promote tumor growth, possibly due to their immunomodulatory activity, 139 and patients treated with ACEis have been reported to have higher rates of kidney cancers. 140 However, several other clinical studies have shown that ACEis do not increase the risk of cancer.…”

Gene-modified tumor vaccine secreting a designer cytokine Hyper-Interleukin-6 is an effective therapy in mice bearing orthotopic renal cell cancer

“…17,18 Other orthotopic tumor models such as prostate or colorectal cancer have also underlined the importance and specificity of an organ-specific microenvironment on tumor biology. 19,20 We have analyzed the efficacy of RENCA-H6 vaccine in various settings resembling particular clinical conditions observed in RCC patients.…”

Ocena potencjału terapeutycznego Temsirolimusu w zaawansowanym stadium renal cell carcinoma

“…Właściwość tę wykazano w badaniach z wykorzystaniem Captoprilu -inhibitora konwertazy angiotensyny, który jest powszechnie stosowany w leczeniu nadciśnienia. Pomimo swoich właściwości przeciwnowotworowych w badaniach przedklinicznych wykazano wpływ Captoprilu na promocję wzrostu guzów immunogennych (takich jak RCC) poprzez osłabienie przeciwnowotworowej odpowiedzi układu immunologicznego, mimo braku ogólnoustrojowych efektów immunosupresji [7,27].…”