NDLI: Immune modulation and apoptosis induction: Two sides of the antitumoral activity of imiquimod

Content Provider	Springer Nature Link
Author	Schön, M. P. Schön, M.
Copyright Year	2004
Abstract	Imiquimod, the first member of the imidazoquinoline family of immune response modifiers, has proven good clinical efficacy against basal cell carcinomas and actinic keratoses in several independent studies. In addition, there is recent evidence that imiquimod is also efficacious against other tumors such as cutaneous metastases of malignant melanoma or vascular tumors. Imiquimod exerts its antitumoral effect, at least in part, through binding to TLR-7 and TLR-8 on dendritic cells followed by secretion of a multitude of proinflammatory cytokines. The net result of this proinflammatory activity is a profound tumor-directed cellular immune response. However, recent experimental and clinical data indicate that imiquimod also possesses considerable direct pro-apoptotic activity against tumor cells both in vitro and in vivo. This novel mode of action appears to be independent of membrane bound death receptors, but involves caspase activation. Induction of apoptosis by imiquimod is, at least in part, presumably mediated through Bcl-2-dependent release of mitochondrial cytochrome c and subsequent activation of caspase-9. The structural analogue, resiquimod, exhibited very limited, if any, such pro-apoptotic activity, possibly due to its lacking ability to enter the cell. Bypassing molecular mechanisms of apoptosis deficiency by a topical compound may be of great utility for treating certain cutaneous tumors.
Starting Page	291
Ending Page	298
Page Count	8
File Format	PDF
ISSN	13608185
Journal	Apoptosis
Volume Number	9
Issue Number	3
e-ISSN	1573675X
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2004-01-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cancer Research Virology Oncology Biochemistry Cell Biology
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science Biochemistry (medical) Cell Biology Clinical Biochemistry Cancer Research Pharmacology

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