Year 2018,
Volume: 46 Issue: 3, 395 - 402, 01.09.2018
Özer Aylin Gürpınar
Emre Kubat
,
Mehmet Ali Onur
References
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Sansaro, M. Amato, J.P. Kitzmiller, M. Pepi, E. Tremoli,
D. Baldassarre, Old and new oral anticoagulants: Food,
herbal medicines and drug interactions. Blood. Rev., 31
(2015) 193-203.
- C. Frost, J. Wang, S.Nepal, A. Schuster, Y.C. Barrett, R.
Mosqueda-Garcia, R.A. Reeves, F. LaCreta, Apixaban,
an oral, direct factor Xa inhibitor: single dose safety,
pharmacokinetics, pharmacodynamics and food effect
in healthy subjects. BJCP. 75 (2012) 476-487.
- G.T. Gerotziafas, I. Mahé, I. Elalamy, New orally active
anticoagulant agents for the prevention and treatment
of venous thromboembolism in cancer patients. Ther.
Clin. Risk. Manag., 10 (2014) 423-426
- A. Di Minno, B Frigerio, G. Spadarella, A. Ravani, D.
Sansaro, M. Amato, J.P. Kitzmiller, M. Pepi, E. Tremoli,
D. Baldassarre, Old and new oral anticoagulants: Food,
herbal medicines and drug interactions. Blood. Rev., 31
(2015) 193-203.
- C. Frost, J. Wang, S.Nepal, A. Schuster, Y.C. Barrett, R.
Mosqueda-Garcia, R.A. Reeves, F. LaCreta, Apixaban,
an oral, direct factor Xa inhibitor: single dose safety,
pharmacokinetics, pharmacodynamics and food effect
in healthy subjects. BJCP. 75 (2012) 476-487.
- G.T. Gerotziafas, I. Mahé, I. Elalamy, New orally active
anticoagulant agents for the prevention and treatment
of venous thromboembolism in cancer patients. Ther.
Clin. Risk. Manag., 10 (2014) 423-426.
Ö.A. Gürpınar et al. / Hacettepe J. Biol. & Chem., 2018, 46 (3), 395–402 401
- V. Der Hulle, P.L. Den Exter, J. Kooiman, J.J.M. Van
der Hoeven, M.V. Heismen, F.A. Klok, Meta-analysis
of the efficacy and safety of new oral anticoagulants
in patients with cancer-associated acute venous
thromboembolism. J. Thromb. Haemost., 12 (2014)
1116-1120.
- M.N. Levine, C. Gu, H.A. Liebman, C.P. Escalante, S.
Solymass, D. Deitchman, L. Ramirez, J. Julian, A
randomized phase II trial of apixaban for the prevention
of thromboembolism in patients with metastatic
cancer. J. Thromb. Haemost., 10 (2012) 807-814.
- L. Guasti, A. Sqizzato, P. Moretto, D., Vigetti, W. Agero,
F. Dentali, A.M. Moresca, L. Campiotti, A.M. Grandi, A.
Passi, In vitro effects of Apixaban on 5 different cancer
cell lines. PlosOne, 12 (2017) 1-19.
- T.A. Hambrough, G.M. Swartz, A. Papathanassiu, G.P.
Vlasuk, W.E. Rote, S.J. Green, V.S. Pribluda, Tissue
Factor/Factor VIIa Inhibitors Block Angiogenesis and
Tumor Growth Through a Nonhemostatic Mechanism.
Cancer Res., 63 (2003) 2997-3000.
- J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C.
Mathers, M. Rebelo, D. M. Parkin, D. Forman, F. Bray,
Cancer incidence and mortality worldwide: Sources,
methods and major patterns in GLOBOCAN 2012. IJC,
136 (2015) 359-386.
- S. Takeuchi, Biology and treatment of cervical
adenocarcinoma. Chin. J. Cancer Res., 28 (2016) 254-
262.
- E.C. Pirog, Cervical Adenocarcinoma: Diagnosis
of Human Papillomavirus–Positive and Human
Papillomavirus–Negative Tumors. Arch. Pathol. Lab.
Med. 241 (2017) 1653–1667.
- J.J. M. Landro, P.T. Pyl, T. Rausch,T. Zichner, M.M.
Tekkedil, A.M. Stütz, A. Jauch, R.S. Aiyar, G. Pau,
N. Delhomme, J. Gagneur, J.O. Korbel, W. Huber,
L.M. Steinmetz, The Genomic and Transcriptomic
Landscape of a HeLa Cell Line. Genes Genoms Genetics.
3 (2013) 1213-1224.
- B.P. Lucey, W.A. Nelson-Rees, G.M. Hutchins, Henrietta
Lacks, HeLa Cells, and Cell Culture Contamination.
Arch. Pathol. Lab. Med. 133 (2009) 1463–1467.
- J.M.E. Contreras-Ortiz, J.C. Vázquez-Chagoyán,
J.S. Martínez-Castañeda, J.G. Estrada-Franco, J.E.
Aparicio-Burgos, J. Acosta-Dibarrat, A. BarbabosaPliego,
Resistance of cervical adenocarcinoma cells
(HeLa) to venom from the scorpion Centruroides
limpidus limpidus. JVATITD. 19 (2013) 1-7.
- P.C. Wong, D.J.P. Pinto, D. Zhang, Preclinical discovery
of apixaban, a direct and orally bioavailable factor Xa
inhibitor. J. Thromb. Thrombolysis. 31 (2011) 478–492.
- P.C. Wong, E.J. Crain, B. Xin, R.R. Wexler, P.Y.S. Lam,
D.J. Pinto, J.M. Luettgen, R.M. Knabb, Apixaban, an
oral, direct and highly selective factor Xa inhibitor: in
vitro, antithrombotic and antihemostatic studies. J.
Thromb. Haemost. 6 (2007) 820-829.
- J.M. Luettegen, R.M. Knabb, K. He, D.J.P. Pinto, A.R.
Rendia, Apixaban inhibition of factor Xa: Microscopic
rate constants and inhibition mechanism in purified
protein systems and in human plasma. J. Enzym. Inhib.
Med. Ch. 26 (2011) 514-526.
- D.J. Pinto, M.J. Orwatt, S. Koch, K.A. Rossi, R.S.
Alexander, A. Smallwood, P.C. Wong, A.R. Rendina,
J.M. Luettegen, R.M. Knabb, K. He, B. Xin, R.R. Wexler,
P.Y. Lam, Discovery of 1-(4-methoxyphenyl)-7-oxo6-(4-(2-oxopiperidin-1-yl)phenyl)
-4,5,6,7-tetrahydro1H-pyrazolo[3,4-c]pyridine-3-carboxamide
(apixaban,BMS-562247), a highly potent, selective, efficacious,
and orally bioavailable inhibitor of blood coagulation
factor Xa. J. Med. Chem. 50 (2007) 5339-5356.
- R. Alam, D. Wahi, R. Singh, D. Sinha, V. Tandan, A.
Graver, Rahisuddin, Design, synthesis, cytotoxicity,
HuTopoIIa inhibitory activity and molecular docking
studies of pyrazole derivatives as potential anticancer
agents. Bioorg. Chem. 69 (2016) 77-90.
- A.T. Baviskar, C. Madaan, P. Mohaptra, V. Jain, A.
Agrawal, S.K. Guchhait, C.N. Kundu, U.C. Banerjee,
N-Fused Imidazoles As Novel Anticancer Agents That
Inhibit Catalytic Activity of Topoisomerase IIr and
Induce Apoptosis in G1/S Phase. J. Med. Chem. 54
(2011) 5013-5030.
- J.J. Champoux, DNA Topoisomerases: Structure,
Function, and Mechanism. Annu. Rev. Biochem. 70
(2001) 369-413.
- R. Alam, A. Alam, A.K. Panda, Rahisuddin, Design,
synthesis and cytotoxicity evaluation of pyrazolyl
pyrazoline and pyrazolyl aminopyrimidine derivatives
as potential anticancer agents. Med. Chem. Res.27
(2018) 560–570.
- H. Li, X. Wu, X. Cheng, Advances in diagnosis and
treatment of metastatic cervical cancer. J. Gynecol.
Oncol. 27 (2016) 1-20.
- S.J. Tsai, Y.X. Ruan, C.C. Lee, M.S. Lee, W.Y. Chiou,
H.Y. Lin, F.C. Hsu, Y.C. Su, S.K. Hung, The incidence
of venous thromboembolism in cervical cancer: a
nationwide population-based study. BMC Research
Notes. 5 (2012) 316-321.
- G. Agnelli, H.R. Buller, A. Cohen, A.S. Gallus, T.C. Lee, R.
Pak, G.E. Raskob, J.I. Weitz, T. Yamabe Oral apixaban
for the treatment of venous thromboembolism in
cancer patients: results from the AMPLIFY trial. J.
Thromb. Haemost. 13 (2015) 2187-2191.
- J.S. Palumbo, K.W. Kombrinck, A.F. Drew, T.S. Grimes,
J.H. Kiser, J.L. Degen, T.H. Bugge, Fibrinogen is an
important determinant of the metastatic potential of
circulating tumor cells. Blood. 96 (2000) 3302-3309.
- T.A. Hembrough, G.M. Swartz, A. Papathanassiu, G.P.
Vlasuk, W.E. Rote, S.J. Green, V.S. Pribluda, Tissue
factor/factor VIIa inhibitors block angiogenesis and
tumor growth through a nonhemostatic mechanism.
Cancer. Res. 63 (2003) 2997-3000.
- J.S. Ventura, F. Faria, I.F.C. Batista, S.M. Simons, D.G.L.
Oliveira, K.L.P. Morais, A.M. Chudzinski-Tavassi, A
Kunitz-type FXa inhibitor affects tumor progression,
hypercoagulable state and triggers apoptosis. Biomed
Pharmacother. 67 (2013) 192-196.
- A.C. Matzdorff, D. Green, Coagulation in Cancer,
Springer Science Business Media, 2009.
- N. Zhang, W. Lou, F. Ji1, L. Qiu, B.K. Tsang, W. Di, Low
molecular weight heparin and cancer survival: clinical
trials and experimental mechanisms. J. Cancer Res.
Clin. Oncol. 142 (2016) 1806-1816.
- E.L. Hellenbart, K.D. Faulkenberg, S.W. Finks,
Evaluation of bleeding in patients receiving direct oral
anticoagulants. Vasc. Health Risk. Manag. 13 (2017)
325-342.
- N.E. Núñez-Navarro, G.F. S. Renato A. Burgos, C.F.
Lagos, N. Fuentes-Ibacache, M.A. Faúndezb, F.C.
Zacconi, Microwave Assisted Synthesis of Novel SixMembered
4-C, 4-O and 4-S Lactams Derivatives:
Characterization and in vitro Biological Evaluation of
Cytotoxicity and Anticoagulant Activity. J. Braz. Chem.
Soc., 28 (2017) 203-207.
Cytotoxic Activity of Apixaban on HeLa Cells: An In vitro Study
Year 2018,
Volume: 46 Issue: 3, 395 - 402, 01.09.2018
Özer Aylin Gürpınar
Emre Kubat
,
Mehmet Ali Onur
Abstract
Apixaban is a new oral anticoagulant which is commonly used in the prophylaxis and treatment of systemic
embolism and deep vein thrombosis. Venous thromboembolic events are important risk factors in cancer
patients. Several studies have suggested that anticoagulant drugs may have an effect on tumor development
and progression. In this study, we aimed to investigate the cytotoxic effect of apixaban on a cancer cell line
HeLa cells derived from human cervical cancer. The viability of HeLa cells was examined at 24 and 48 hours of
incubation and apixaban showed a cytotoxic effect in the highest dilution. In other dilutions, cell viability was
similar to the control group. These results show that apixaban may reduce proliferation of cancer cells at high
concentrations.
References
- A. Di Minno, B Frigerio, G. Spadarella, A. Ravani, D.
Sansaro, M. Amato, J.P. Kitzmiller, M. Pepi, E. Tremoli,
D. Baldassarre, Old and new oral anticoagulants: Food,
herbal medicines and drug interactions. Blood. Rev., 31
(2015) 193-203.
- C. Frost, J. Wang, S.Nepal, A. Schuster, Y.C. Barrett, R.
Mosqueda-Garcia, R.A. Reeves, F. LaCreta, Apixaban,
an oral, direct factor Xa inhibitor: single dose safety,
pharmacokinetics, pharmacodynamics and food effect
in healthy subjects. BJCP. 75 (2012) 476-487.
- G.T. Gerotziafas, I. Mahé, I. Elalamy, New orally active
anticoagulant agents for the prevention and treatment
of venous thromboembolism in cancer patients. Ther.
Clin. Risk. Manag., 10 (2014) 423-426
- A. Di Minno, B Frigerio, G. Spadarella, A. Ravani, D.
Sansaro, M. Amato, J.P. Kitzmiller, M. Pepi, E. Tremoli,
D. Baldassarre, Old and new oral anticoagulants: Food,
herbal medicines and drug interactions. Blood. Rev., 31
(2015) 193-203.
- C. Frost, J. Wang, S.Nepal, A. Schuster, Y.C. Barrett, R.
Mosqueda-Garcia, R.A. Reeves, F. LaCreta, Apixaban,
an oral, direct factor Xa inhibitor: single dose safety,
pharmacokinetics, pharmacodynamics and food effect
in healthy subjects. BJCP. 75 (2012) 476-487.
- G.T. Gerotziafas, I. Mahé, I. Elalamy, New orally active
anticoagulant agents for the prevention and treatment
of venous thromboembolism in cancer patients. Ther.
Clin. Risk. Manag., 10 (2014) 423-426.
Ö.A. Gürpınar et al. / Hacettepe J. Biol. & Chem., 2018, 46 (3), 395–402 401
- V. Der Hulle, P.L. Den Exter, J. Kooiman, J.J.M. Van
der Hoeven, M.V. Heismen, F.A. Klok, Meta-analysis
of the efficacy and safety of new oral anticoagulants
in patients with cancer-associated acute venous
thromboembolism. J. Thromb. Haemost., 12 (2014)
1116-1120.
- M.N. Levine, C. Gu, H.A. Liebman, C.P. Escalante, S.
Solymass, D. Deitchman, L. Ramirez, J. Julian, A
randomized phase II trial of apixaban for the prevention
of thromboembolism in patients with metastatic
cancer. J. Thromb. Haemost., 10 (2012) 807-814.
- L. Guasti, A. Sqizzato, P. Moretto, D., Vigetti, W. Agero,
F. Dentali, A.M. Moresca, L. Campiotti, A.M. Grandi, A.
Passi, In vitro effects of Apixaban on 5 different cancer
cell lines. PlosOne, 12 (2017) 1-19.
- T.A. Hambrough, G.M. Swartz, A. Papathanassiu, G.P.
Vlasuk, W.E. Rote, S.J. Green, V.S. Pribluda, Tissue
Factor/Factor VIIa Inhibitors Block Angiogenesis and
Tumor Growth Through a Nonhemostatic Mechanism.
Cancer Res., 63 (2003) 2997-3000.
- J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C.
Mathers, M. Rebelo, D. M. Parkin, D. Forman, F. Bray,
Cancer incidence and mortality worldwide: Sources,
methods and major patterns in GLOBOCAN 2012. IJC,
136 (2015) 359-386.
- S. Takeuchi, Biology and treatment of cervical
adenocarcinoma. Chin. J. Cancer Res., 28 (2016) 254-
262.
- E.C. Pirog, Cervical Adenocarcinoma: Diagnosis
of Human Papillomavirus–Positive and Human
Papillomavirus–Negative Tumors. Arch. Pathol. Lab.
Med. 241 (2017) 1653–1667.
- J.J. M. Landro, P.T. Pyl, T. Rausch,T. Zichner, M.M.
Tekkedil, A.M. Stütz, A. Jauch, R.S. Aiyar, G. Pau,
N. Delhomme, J. Gagneur, J.O. Korbel, W. Huber,
L.M. Steinmetz, The Genomic and Transcriptomic
Landscape of a HeLa Cell Line. Genes Genoms Genetics.
3 (2013) 1213-1224.
- B.P. Lucey, W.A. Nelson-Rees, G.M. Hutchins, Henrietta
Lacks, HeLa Cells, and Cell Culture Contamination.
Arch. Pathol. Lab. Med. 133 (2009) 1463–1467.
- J.M.E. Contreras-Ortiz, J.C. Vázquez-Chagoyán,
J.S. Martínez-Castañeda, J.G. Estrada-Franco, J.E.
Aparicio-Burgos, J. Acosta-Dibarrat, A. BarbabosaPliego,
Resistance of cervical adenocarcinoma cells
(HeLa) to venom from the scorpion Centruroides
limpidus limpidus. JVATITD. 19 (2013) 1-7.
- P.C. Wong, D.J.P. Pinto, D. Zhang, Preclinical discovery
of apixaban, a direct and orally bioavailable factor Xa
inhibitor. J. Thromb. Thrombolysis. 31 (2011) 478–492.
- P.C. Wong, E.J. Crain, B. Xin, R.R. Wexler, P.Y.S. Lam,
D.J. Pinto, J.M. Luettgen, R.M. Knabb, Apixaban, an
oral, direct and highly selective factor Xa inhibitor: in
vitro, antithrombotic and antihemostatic studies. J.
Thromb. Haemost. 6 (2007) 820-829.
- J.M. Luettegen, R.M. Knabb, K. He, D.J.P. Pinto, A.R.
Rendia, Apixaban inhibition of factor Xa: Microscopic
rate constants and inhibition mechanism in purified
protein systems and in human plasma. J. Enzym. Inhib.
Med. Ch. 26 (2011) 514-526.
- D.J. Pinto, M.J. Orwatt, S. Koch, K.A. Rossi, R.S.
Alexander, A. Smallwood, P.C. Wong, A.R. Rendina,
J.M. Luettegen, R.M. Knabb, K. He, B. Xin, R.R. Wexler,
P.Y. Lam, Discovery of 1-(4-methoxyphenyl)-7-oxo6-(4-(2-oxopiperidin-1-yl)phenyl)
-4,5,6,7-tetrahydro1H-pyrazolo[3,4-c]pyridine-3-carboxamide
(apixaban,BMS-562247), a highly potent, selective, efficacious,
and orally bioavailable inhibitor of blood coagulation
factor Xa. J. Med. Chem. 50 (2007) 5339-5356.
- R. Alam, D. Wahi, R. Singh, D. Sinha, V. Tandan, A.
Graver, Rahisuddin, Design, synthesis, cytotoxicity,
HuTopoIIa inhibitory activity and molecular docking
studies of pyrazole derivatives as potential anticancer
agents. Bioorg. Chem. 69 (2016) 77-90.
- A.T. Baviskar, C. Madaan, P. Mohaptra, V. Jain, A.
Agrawal, S.K. Guchhait, C.N. Kundu, U.C. Banerjee,
N-Fused Imidazoles As Novel Anticancer Agents That
Inhibit Catalytic Activity of Topoisomerase IIr and
Induce Apoptosis in G1/S Phase. J. Med. Chem. 54
(2011) 5013-5030.
- J.J. Champoux, DNA Topoisomerases: Structure,
Function, and Mechanism. Annu. Rev. Biochem. 70
(2001) 369-413.
- R. Alam, A. Alam, A.K. Panda, Rahisuddin, Design,
synthesis and cytotoxicity evaluation of pyrazolyl
pyrazoline and pyrazolyl aminopyrimidine derivatives
as potential anticancer agents. Med. Chem. Res.27
(2018) 560–570.
- H. Li, X. Wu, X. Cheng, Advances in diagnosis and
treatment of metastatic cervical cancer. J. Gynecol.
Oncol. 27 (2016) 1-20.
- S.J. Tsai, Y.X. Ruan, C.C. Lee, M.S. Lee, W.Y. Chiou,
H.Y. Lin, F.C. Hsu, Y.C. Su, S.K. Hung, The incidence
of venous thromboembolism in cervical cancer: a
nationwide population-based study. BMC Research
Notes. 5 (2012) 316-321.
- G. Agnelli, H.R. Buller, A. Cohen, A.S. Gallus, T.C. Lee, R.
Pak, G.E. Raskob, J.I. Weitz, T. Yamabe Oral apixaban
for the treatment of venous thromboembolism in
cancer patients: results from the AMPLIFY trial. J.
Thromb. Haemost. 13 (2015) 2187-2191.
- J.S. Palumbo, K.W. Kombrinck, A.F. Drew, T.S. Grimes,
J.H. Kiser, J.L. Degen, T.H. Bugge, Fibrinogen is an
important determinant of the metastatic potential of
circulating tumor cells. Blood. 96 (2000) 3302-3309.
- T.A. Hembrough, G.M. Swartz, A. Papathanassiu, G.P.
Vlasuk, W.E. Rote, S.J. Green, V.S. Pribluda, Tissue
factor/factor VIIa inhibitors block angiogenesis and
tumor growth through a nonhemostatic mechanism.
Cancer. Res. 63 (2003) 2997-3000.
- J.S. Ventura, F. Faria, I.F.C. Batista, S.M. Simons, D.G.L.
Oliveira, K.L.P. Morais, A.M. Chudzinski-Tavassi, A
Kunitz-type FXa inhibitor affects tumor progression,
hypercoagulable state and triggers apoptosis. Biomed
Pharmacother. 67 (2013) 192-196.
- A.C. Matzdorff, D. Green, Coagulation in Cancer,
Springer Science Business Media, 2009.
- N. Zhang, W. Lou, F. Ji1, L. Qiu, B.K. Tsang, W. Di, Low
molecular weight heparin and cancer survival: clinical
trials and experimental mechanisms. J. Cancer Res.
Clin. Oncol. 142 (2016) 1806-1816.
- E.L. Hellenbart, K.D. Faulkenberg, S.W. Finks,
Evaluation of bleeding in patients receiving direct oral
anticoagulants. Vasc. Health Risk. Manag. 13 (2017)
325-342.
- N.E. Núñez-Navarro, G.F. S. Renato A. Burgos, C.F.
Lagos, N. Fuentes-Ibacache, M.A. Faúndezb, F.C.
Zacconi, Microwave Assisted Synthesis of Novel SixMembered
4-C, 4-O and 4-S Lactams Derivatives:
Characterization and in vitro Biological Evaluation of
Cytotoxicity and Anticoagulant Activity. J. Braz. Chem.
Soc., 28 (2017) 203-207.