Statins Impair Antitumor Effects of Rituximab by Inducing Conformational Changes of CD20

Winiarska, Magdalena; Bil, Jacek; Wilczek, Ewa; Wilczyński, Grzegorz M.; Lekka, Małgorzata; Engelberts, Patrick J.; Mackus, Wendy J.M.; Górska, Elżbieta; Bojarski, Łukasz; Stokłosa, Tomasz; Nowis, Dominika; Kurzaj, Zuzanna; Makowski, Marcin; Głodkowska, Eliza; Issat, Tadeusz; Mrówka, Piotr; Lasek, Witold; Dąbrowska‐Iwanicka, Anna; Basak, Grzegorz; Wasik, M; Warzocha, Krzysztof; Siński, Maciej; Gaciong, Zbigniew; Jakóbisiak, Marek; Parren, Paul W.H.I.; Gołąb, Jakub

doi:10.1371/journal.pmed.0050064

Cited by 121 publications

(113 citation statements)

References 42 publications

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“…statins and berberine may not only act as therapeutics capable of potentiating antitumor effects of other drugs, but may also selectively neutralize some of their undesirable effects (41). on the other hand statins might occasionally inhibit or even neutralize beneficial antitumor effects of established antitumor therapeutics (64).…”

Section: Discussionmentioning

confidence: 99%

Antitumor effects of the combination of cholesterol reducing drugs

Issat

Nowis²,

Bil³

et al. 2011

Oncol Rep

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Abstract. there are a number of potential mechanisms linking cholesterol homeostasis to processes that are tightly linked with carcinogenesis. statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMg-coAr), the rate-limiting enzyme in the mevalonic acid synthesis pathway, exert cytostatic and cytotoxic effects towards tumor cells. It seems that the cytostatic and cytotoxic effects of statins result from blocking protein prenylation, leading to inhibition of isoprenoid compound synthesis. Another compound which affects cholesterol metabolism is the plant alkaloid berberine. the aim of this study was to investigate potential antitumor effects of lovastatin combined with berberine. combined with berberine, lovastatin appeared to exert potentiated cytostatic and/or cytotoxic effects against human MDA-MB231 breast cancer and murine panc 02 pancreatic cancer cells. the obtained results indicated that the effect of berberine is not dependent on blocking protein prenylation in cells, and the toxic effect of lovastatin combined with berberine is reversed by addition of the substrates of this pathway to the level brought out by lovastatin alone. lovastatin-berberine combination caused cell cycle inhibition in g1 phase after 48 h of incubation with drugs. In a panc 02 pancreatic cancer model in mice, lovastatin-berberine combination slightly, but significantly, slowed down tumor growth. taking into account the number of patients treated with the investigated drugs one may suppose that the described interactions may be of clinical value. Introductioncholesterol-reducing agents continuously attract enormous interest not only because of their beneficial cardiovascular effects, but also due to their influence on numerous physiological and pathophysiological processes (1-3). For example, statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMg-coA) reductase target mevalonate pathway of cholesterol synthesis and impair production of isoprenoid compounds such as dolichol, ubiquinone and mevalonate-derived prenyl groups that are attached post-translationally to approximately 1% of all cellular proteins (4,5). By affecting cellular cholesterol synthesis statins also influence the formation of lipid rafts which are water insoluble plasma membrane microdomains enriched in receptors and signal transduction molecules (6). the interference with so many critical biochemical processes makes their effects extremely pleiotropic. Although statins have so far been approved only for prophylaxis or treatment of cardiovascular diseases they also show some promising therapeutic activity in the management of Alzheimer's disease, osteoporosis, graft rejection and cancer (7,8).Despite alarming results of carcinogenicity studies in rodents (9-11) clinical observations did not show an overall increase in cancer incidence or mortality among statin users (12)(13)(14). In fact statins were rather associated with reductions in the incidence of colorectal, prostate and lung cancers as well as in melanoma (15...

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Section: Discussionmentioning

confidence: 99%

Antitumor effects of the combination of cholesterol reducing drugs

Issat

Nowis²,

Bil³

et al. 2011

Oncol Rep

Self Cite

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“…В нескольких доклинических исследованиях было обнаружено неблагоприятное воздействие статинов на эф-фективность РТМ у пациентов с гематологическими зло-качественными новообразованиями [101,102]. При РА до-казательства негативного влияния статинов на эффектив-ность РТМ отсутствуют [103,104].…”

Section: рекомендация 6 скрининг бессимптомных атб с ис-пользованиемunclassified

According to the Materials of the 2015/2016 New European League Against Rheumatism (Eular) Guidelines for Reducing Cardiovascular Risk in Patients With Inflammatory Arthritis: General Characterization and Discussion Problems

Попкова¹,

Новикова²

2018

rsp

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According to the materials of the 2015/2016 new European League Against Rheumatism (EULAR) guidelines for reducing cardiovascular risk in patients with inflammatory arthritis. The authors identify three main principles of prevention of cardiovascular diseases in rheumatoid arthritis and other chronic inflammatory arthritis and provide a general characterization of the guidelines, by reviewing the discussion problems.

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“…114 Statins have the potential to alter the conformation of the CD20 receptor, which may change the effect of rituximab. 217 …”

Section: Intravitreal Rituximabmentioning

confidence: 99%