Journal
ANTI-CANCER DRUGS
Volume 33, Issue 1, Pages E21-E27Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0000000000001146
Keywords
cancer therapy; nucleolus; nucleolar stress; natural products; ribosome biogenesis
Categories
Funding
- Natural Science Foundation of China [81872167, 81472496]
- Natural Science Foundation of Hunan [2019JJ40193]
- Key Project of Department of Education of Hunan Province [14A089]
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The nucleolus, a site of ribosome biogenesis, has been found to play a crucial role in cancer development. Recent studies have shown that the nucleolus controls various cellular functions related to cancer development and induction of nucleolar stress has emerged as a promising therapeutic approach. Natural products have been discovered as effective inducers of nucleolar stress, paving the way for novel anti-cancer drugs.
The nucleolus is the site of ribosome biogenesis and is found to play an important role in stress sensing. For over 100 years, the increase in the size and number of nucleoli has been considered as a marker of aggressive tumors. Despite this, the contribution of the nucleolus and the biologic processes mediated by it to cancer pathogenesis has been largely overlooked. This state has been changed over the recent decades with the demonstration that the nucleolus controls numerous cellular functions associated with cancer development. Induction of nucleolar stress has recently been regarded as being superior to conventional cytotoxic/cytostatic strategy in that it is more selective to neoplastic cells while sparing normal cells. Natural products represent an excellent source of bioactive molecules and some of them have been found to be able to induce nucleolar stress. The demonstration of these nucleolar stress-inducing natural products has paved the way for a new therapeutic approach to more delicate tumor cell-killing. This review provides a contemporary summary of the role of the nucleolus as a novel promising target for cancer therapy, with particular emphasis on natural products as an exciting new class of anti-cancer drugs with nucleolar stress-inducing properties.
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