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Revista do Instituto de Medicina Tropical de São Paulo

versão On-line ISSN 1678-9946

Rev. Inst. Med. trop. S. Paulo vol.55 no.2 São Paulo mar./abr. 2013 

Letter to the Editor


Shailendra Kapoor

1University of Illinois at Chicago, 75 Kristin Circle 413, Schaumburg Illinois, 60195, Chicago, IL, USA, , E-mail:,

November 18, 2012

Dear Sir

BRUGES et al. have reported interesting data in their article 1 . Interestingly, recent data suggests that staurosporine can inhibit tumor growth in a number of systemic malignancies.

For instance, staurosporine demonstrates anti-proliferative effects in prostate carcinomas. It causes significant attenuation of cyclin D1 expression within the cancerous cells 2 . It also increases the translocation of cytochrome c to the cytoplasm and has an enhancing effect on intra- tumoral apoptosis. As a result it markedly decreases tumor growth in prostate malignancies. Besides this, staurosporine also up-regulates the expression of TIMP-1 as a result of increased transcription. This further attenuates tumor invasiveness. Staurosporine also causes increased expression of tau in the cancerous cells 8 . As a result staurosporine increases differentiation of the cancerous cells to cells with neuronal features. As a consequence, tumor invasiveness is attenuated by as much as 20%. It also augments PARP inactivation at the same time 9 .

Similar effects are seen in non-small cell lung carcinomas. Staurosporine augments the activity of thymidine kinase-2 within the tumor 4 . As a result, it increases the chemo-sensitivity of lung tumors to chemotherapeutic agents such as gemcitabine and cisplatin. dCK activity is also increased simultaneously while E2F expression is decreased. At the same time, staurosporine down- regulates RNR expression 7 . Retinoblastoma gene product expression is also altered by staurosporine 5 . Similar effects are seen in gastrointestinal malignancies such as gastric carcinomas. Staurosporine administration results in up- regulation of the p21WAF1 gene 6 . As a result, there is augmented G2/ M phase arrest. Apoptosis is markedly increased. As a result tumor growth is markedly attenuated.

The above examples clearly illustrate the significant anti-proliferative and apoptotic features of staurosporine and the need for further studies to explore and harness its anti-neoplastic effects.


1. Bruges G, Betancourt M, March M, Sanchez E, Mijares A. Apoptotic-like activity of staurosporine in axenic cultures of Trypanosoma evansi. Rev Inst Med Trop Sao Paulo. 2012;54:103-8. [ Links ]

2. Gao L, Yang JR, Peng YY, Pan TJ. Effects of staurosporine on the proliferation and apoptosis of prostate cancer PC-3 cells. Zhonghua Nan Ke Xue. 2011;17:884-7. [ Links ]

3. Ha MW, Hou KZ, Liu YP, Yuan Y. Effect of staurosporine on cycle of human gastric cancer cells. World J Gastroenterol. 2004;10:161-6. [ Links ]

4. Marcelli M, Marani M, Li X, Sturgis L, Haidacher SJ, Trial JA, et al. Heterogeneous apoptotic responses of prostate cancer cell lines identify an association between sensitivity to staurosporine-induced apoptosis, expression of Bcl-2 family members, and caspase activation. Prostate. 2000;42:260-73. [ Links ]

5. Monnerat C, Henriksson R, Le Chevalier T, Novello S, Berthaud P, Faivre S, et al. Phase I study of PKC412 (N-benzoyl-staurosporine), a novel oral protein kinase C inhibitor, combined with gemcitabine and cisplatin in patients with non-small-cell lung cancer. Ann Oncol. 2004;15:316-23. [ Links ]

6. Shimizu E, Zhao MR, Nakanishi H, Yamamoto A, Yoshida S, Takada M, et al. Differing effects of staurosporine and UCN-01 on RB protein phosphorylation and expression of lung cancer cell lines. Oncology. 1996;53:494-504. [ Links ]

7. Sigmond J, Bergman AM, Leon LG, Loves WJ, Hoebe EK, Peters GJ. Staurosporine increases toxicity of gemcitabine in non-small cell lung cancer cells: role of protein kinase C, deoxycytidine kinase and ribonucleotide reductase. Anticancer Drugs. 2010;21:591-9. [ Links ]

8. Tachibana K, Shimizu T, Tonami K, Takeda K. Staurosporine enhances the expression of tissue inhibitor of metalloproteinase-1 in human prostate cancer cells. Biochem Biophys Res Commun. 2002;295:489-94. [ Links ]

9. Takahashi N, Shimizu T, Takeda K. Low-dose staurosporine suppresses proliferation and induces neurites in human prostatic cancer TSU-Pr1 cells. Prostate. 2000;44:328-33. [ Links ]

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