Monomethyl auristatin E Exhibits Potent Cytotoxic Activity against Human Cancer Cell Lines SKBR3 and HEK293
<h2>Background: Monomethyl auristatin E (MMAE) is a synthetic analog of dolastatin 10, a compound originally isolated from the marine mollusk. MMAE, as a highly potent microtubule inhibitor, exerts its potent cytotoxic effect by inhibiting microtubule assembly, tubulin-dependent GTP hydrolysis...
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| Format: | Article |
| Language: | English |
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Shahid Beheshti University of Medical Sciences
2017-10-01
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| Series: | Novelty in Biomedicine |
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| Online Access: | http://journals.sbmu.ac.ir/nbm/article/view/15221 |
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| author | Meghdad Abdollahpour-Alitappeh Sepand Razavi-vakhshourpour Majid Lotfinia Saeed Jahandideh Hamid Najminejad Saeed Balalaie Reza Moazzami Elnaz Shams Mahdi Habibi-Anbouhi Mohsen Abolhassani |
| author_facet | Meghdad Abdollahpour-Alitappeh Sepand Razavi-vakhshourpour Majid Lotfinia Saeed Jahandideh Hamid Najminejad Saeed Balalaie Reza Moazzami Elnaz Shams Mahdi Habibi-Anbouhi Mohsen Abolhassani |
| author_sort | Meghdad Abdollahpour-Alitappeh |
| collection | DOAJ |
| description | <h2>Background: Monomethyl auristatin E (MMAE) is a synthetic analog of dolastatin 10, a compound originally isolated from the marine mollusk. MMAE, as a highly potent microtubule inhibitor, exerts its potent cytotoxic effect by inhibiting microtubule assembly, tubulin-dependent GTP hydrolysis and microtubes polymerization. This molecule, by itself, lacks the tumor specificity required to elicit therapeutic benefit. Nevertheless, the extremely cytotoxic potential of MMAE could be harnessed in the form of MMAE-antibody conjugates. The aim of the present study was to evaluate the cytotoxic activity of MMAE against breast (SKBR3) and kidney (HEK293) cancer cell lines in an in vitro cell-based assay.</h2><p><strong>M</strong><strong>aterials and Methods: </strong>SKBR3 and HEK293 cells were treated with different concentrations ranging from 0.002048, 0.01024, 0.0512, 0.256, 1.28, 6.4, 32, 160, 800 and 4000 nM of MMAE, and cell viability was determined after 72 hours using an MTT colorimetric assay. The effect of MMAE was regularly monitored by direct observation using an invert microscope.</p><p><strong>R</strong><strong>es</strong><strong>ults: </strong>Microscopic observation showed that there was a concentration-dependent increase in cell death. Results from the MTT assay revealed a statistically significant loss of viability (P<0.0001) at concentrations ranging from 0.01024 to 4000 nM in SKBR3 cells, and 0.0512 to 4000 nM in HEK293 cells. Our findings showed that MMAE inhibited the growth of SKBR3 and HEK293 cells in a concentration-dependent manner, with IC50 values of 3.27 ± 0.42 and 4.24 ± 0.37 nM, respectively.</p><p><strong>C</strong><strong>onclusion: </strong>MMAE was able to significantly inhibit cell growth at nanomolar concentrations, emphasizing its great potential for the development of antibody-drug conjugates.</p> |
| first_indexed | 2024-12-19T23:17:22Z |
| format | Article |
| id | doaj.art-b946ef9810b34934a8e03874e4ea39e2 |
| institution | Directory Open Access Journal |
| issn | 2345-3346 2345-3907 |
| language | English |
| last_indexed | 2024-12-19T23:17:22Z |
| publishDate | 2017-10-01 |
| publisher | Shahid Beheshti University of Medical Sciences |
| record_format | Article |
| series | Novelty in Biomedicine |
| spelling | doaj.art-b946ef9810b34934a8e03874e4ea39e22022-12-21T20:02:04ZengShahid Beheshti University of Medical SciencesNovelty in Biomedicine2345-33462345-39072017-10-015414515110.22037/nbm.v5i4.152219500Monomethyl auristatin E Exhibits Potent Cytotoxic Activity against Human Cancer Cell Lines SKBR3 and HEK293Meghdad Abdollahpour-Alitappeh0Sepand Razavi-vakhshourpour1Majid Lotfinia2Saeed Jahandideh3Hamid Najminejad4Saeed Balalaie5Reza Moazzami6Elnaz Shams7Mahdi Habibi-Anbouhi8Mohsen Abolhassani9Hybridoma Lab, Immunology Department, Pasteur Institute of Iran, Tehran, IranHybridoma Lab, Immunology Department, Pasteur Institute of Iran, Tehran, IranDepartment of Biochemistry, Pasteur Institute of Iran, Tehran, IranDepartment of Biochemistry, Pasteur Institute of Iran, Tehran, IranHybridoma Lab, Immunology Department, Pasteur Institute of Iran, Tehran, IranPeptide Chemistry Research Group, K.N. Toosi University of Technology, Tehran, IranBiotechnology Research Center, Pasteur Institute of Iran, Tehran, IranBiotechnology Research Center, Pasteur Institute of Iran, Tehran, IranNational Cell Bank of Iran, Pasteur Institute of Iran, Tehran, IranHybridoma Lab, Immunology Department, Pasteur Institute of Iran, Tehran, Iran<h2>Background: Monomethyl auristatin E (MMAE) is a synthetic analog of dolastatin 10, a compound originally isolated from the marine mollusk. MMAE, as a highly potent microtubule inhibitor, exerts its potent cytotoxic effect by inhibiting microtubule assembly, tubulin-dependent GTP hydrolysis and microtubes polymerization. This molecule, by itself, lacks the tumor specificity required to elicit therapeutic benefit. Nevertheless, the extremely cytotoxic potential of MMAE could be harnessed in the form of MMAE-antibody conjugates. The aim of the present study was to evaluate the cytotoxic activity of MMAE against breast (SKBR3) and kidney (HEK293) cancer cell lines in an in vitro cell-based assay.</h2><p><strong>M</strong><strong>aterials and Methods: </strong>SKBR3 and HEK293 cells were treated with different concentrations ranging from 0.002048, 0.01024, 0.0512, 0.256, 1.28, 6.4, 32, 160, 800 and 4000 nM of MMAE, and cell viability was determined after 72 hours using an MTT colorimetric assay. The effect of MMAE was regularly monitored by direct observation using an invert microscope.</p><p><strong>R</strong><strong>es</strong><strong>ults: </strong>Microscopic observation showed that there was a concentration-dependent increase in cell death. Results from the MTT assay revealed a statistically significant loss of viability (P<0.0001) at concentrations ranging from 0.01024 to 4000 nM in SKBR3 cells, and 0.0512 to 4000 nM in HEK293 cells. Our findings showed that MMAE inhibited the growth of SKBR3 and HEK293 cells in a concentration-dependent manner, with IC50 values of 3.27 ± 0.42 and 4.24 ± 0.37 nM, respectively.</p><p><strong>C</strong><strong>onclusion: </strong>MMAE was able to significantly inhibit cell growth at nanomolar concentrations, emphasizing its great potential for the development of antibody-drug conjugates.</p>http://journals.sbmu.ac.ir/nbm/article/view/15221Monomethyl auristatin EcytotoxicityAntibody-drug conjugateSKBR3HEK293 |
| spellingShingle | Meghdad Abdollahpour-Alitappeh Sepand Razavi-vakhshourpour Majid Lotfinia Saeed Jahandideh Hamid Najminejad Saeed Balalaie Reza Moazzami Elnaz Shams Mahdi Habibi-Anbouhi Mohsen Abolhassani Monomethyl auristatin E Exhibits Potent Cytotoxic Activity against Human Cancer Cell Lines SKBR3 and HEK293 Novelty in Biomedicine Monomethyl auristatin E cytotoxicity Antibody-drug conjugate SKBR3 HEK293 |
| title | Monomethyl auristatin E Exhibits Potent Cytotoxic Activity against Human Cancer Cell Lines SKBR3 and HEK293 |
| title_full | Monomethyl auristatin E Exhibits Potent Cytotoxic Activity against Human Cancer Cell Lines SKBR3 and HEK293 |
| title_fullStr | Monomethyl auristatin E Exhibits Potent Cytotoxic Activity against Human Cancer Cell Lines SKBR3 and HEK293 |
| title_full_unstemmed | Monomethyl auristatin E Exhibits Potent Cytotoxic Activity against Human Cancer Cell Lines SKBR3 and HEK293 |
| title_short | Monomethyl auristatin E Exhibits Potent Cytotoxic Activity against Human Cancer Cell Lines SKBR3 and HEK293 |
| title_sort | monomethyl auristatin e exhibits potent cytotoxic activity against human cancer cell lines skbr3 and hek293 |
| topic | Monomethyl auristatin E cytotoxicity Antibody-drug conjugate SKBR3 HEK293 |
| url | http://journals.sbmu.ac.ir/nbm/article/view/15221 |
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