MBP-11901 Inhibits Tumor Growth of Hepatocellular Carcinoma through Multitargeted Inhibition of Receptor Tyrosine Kinases
Hepatocellular carcinomas (HCCs) are aggressive tumors with a poor prognosis. Approved first-line treatments include sorafenib, lenvatinib, and a combination of atezolizumab and bevacizumab; however, they do not cure HCC. We investigated MBP-11901 as a drug candidate for HCC. Cell proliferation and...
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2022-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/8/1994 |
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| author | Hyun Jin Park Garam Choi Seongmin Ha Yesl Kim Min-Jin Choi Minsup Kim Md. Kamrul Islam Yongmin Chang Tae-Jun Kwon Dongkyu Kim Eunbee Jang Tae Hwan Kim Sha Joung Chang Yeoun-Hee Kim |
| author_facet | Hyun Jin Park Garam Choi Seongmin Ha Yesl Kim Min-Jin Choi Minsup Kim Md. Kamrul Islam Yongmin Chang Tae-Jun Kwon Dongkyu Kim Eunbee Jang Tae Hwan Kim Sha Joung Chang Yeoun-Hee Kim |
| author_sort | Hyun Jin Park |
| collection | DOAJ |
| description | Hepatocellular carcinomas (HCCs) are aggressive tumors with a poor prognosis. Approved first-line treatments include sorafenib, lenvatinib, and a combination of atezolizumab and bevacizumab; however, they do not cure HCC. We investigated MBP-11901 as a drug candidate for HCC. Cell proliferation and cytotoxicity were evaluated using normal and cancer human liver cell lines, while Western blotting and flow cytometry evaluated apoptosis. The anticancer effect of MBP-11901 was verified in vitro through migration, invasion, colony formation, and JC-1 MMP assays. In mouse models, the tumor volume, tumor weight, and bodyweight were measured, and cancer cell proliferation and apoptosis were analyzed. The toxicity of MBP-11901 was investigated through GOT/GPT and histological analyses in the liver and kidney. The signaling mechanism of MBP-11901 was investigated through kinase assays, phosphorylation analysis, and in silico docking simulations. Results. MBP-11901 was effective against various human HCC cell lines, leading to the disappearance of most tumors when administered orally in animal models. This effect was dose-dependent, with no differences in efficacy according to administration intervals. MBP-11901 induced anticancer effects by targeting the signaling mechanisms of FLT3, VEGFR2, c-KIT, and PDGFRβ. MBP-11901 is suggested as a novel therapeutic agent for the treatment of advanced or unresectable liver cancer. |
| first_indexed | 2024-03-09T11:03:41Z |
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| id | doaj.art-e779cec764fe4fb384880068f117c135 |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T11:03:41Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e779cec764fe4fb384880068f117c1352023-12-01T01:08:01ZengMDPI AGCancers2072-66942022-04-01148199410.3390/cancers14081994MBP-11901 Inhibits Tumor Growth of Hepatocellular Carcinoma through Multitargeted Inhibition of Receptor Tyrosine KinasesHyun Jin Park0Garam Choi1Seongmin Ha2Yesl Kim3Min-Jin Choi4Minsup Kim5Md. Kamrul Islam6Yongmin Chang7Tae-Jun Kwon8Dongkyu Kim9Eunbee Jang10Tae Hwan Kim11Sha Joung Chang12Yeoun-Hee Kim13R&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, KoreaR&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, KoreaInstitute of Biomedical Engineering Research, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu 41944, KoreaR&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, KoreaR&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, KoreaInCerebro Drug Discovery Institute, Seoul 01811, KoreaInstitute of Biomedical Engineering Research, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu 41944, KoreaInstitute of Biomedical Engineering Research, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu 41944, KoreaPreclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation, 80, Cheombok-ro, Dong-gu, Daegu 41061, KoreaPreclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation, 80, Cheombok-ro, Dong-gu, Daegu 41061, KoreaCollege of Pharmacy, Daegu Catholic University, 13-13, Hayang-ro, Hayang-eup, Gyeongsan-si 38430, KoreaCollege of Pharmacy, Daegu Catholic University, 13-13, Hayang-ro, Hayang-eup, Gyeongsan-si 38430, KoreaR&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, KoreaR&D Center, Etnova Therapeutics Corp., 124, Sagimakgol-ro, Jungwon-gu, Seongnam-si 13207, KoreaHepatocellular carcinomas (HCCs) are aggressive tumors with a poor prognosis. Approved first-line treatments include sorafenib, lenvatinib, and a combination of atezolizumab and bevacizumab; however, they do not cure HCC. We investigated MBP-11901 as a drug candidate for HCC. Cell proliferation and cytotoxicity were evaluated using normal and cancer human liver cell lines, while Western blotting and flow cytometry evaluated apoptosis. The anticancer effect of MBP-11901 was verified in vitro through migration, invasion, colony formation, and JC-1 MMP assays. In mouse models, the tumor volume, tumor weight, and bodyweight were measured, and cancer cell proliferation and apoptosis were analyzed. The toxicity of MBP-11901 was investigated through GOT/GPT and histological analyses in the liver and kidney. The signaling mechanism of MBP-11901 was investigated through kinase assays, phosphorylation analysis, and in silico docking simulations. Results. MBP-11901 was effective against various human HCC cell lines, leading to the disappearance of most tumors when administered orally in animal models. This effect was dose-dependent, with no differences in efficacy according to administration intervals. MBP-11901 induced anticancer effects by targeting the signaling mechanisms of FLT3, VEGFR2, c-KIT, and PDGFRβ. MBP-11901 is suggested as a novel therapeutic agent for the treatment of advanced or unresectable liver cancer.https://www.mdpi.com/2072-6694/14/8/1994hepatocellular carcinomatargeted therapytyrosine kinase inhibitoranticancer agentcomplete response |
| spellingShingle | Hyun Jin Park Garam Choi Seongmin Ha Yesl Kim Min-Jin Choi Minsup Kim Md. Kamrul Islam Yongmin Chang Tae-Jun Kwon Dongkyu Kim Eunbee Jang Tae Hwan Kim Sha Joung Chang Yeoun-Hee Kim MBP-11901 Inhibits Tumor Growth of Hepatocellular Carcinoma through Multitargeted Inhibition of Receptor Tyrosine Kinases Cancers hepatocellular carcinoma targeted therapy tyrosine kinase inhibitor anticancer agent complete response |
| title | MBP-11901 Inhibits Tumor Growth of Hepatocellular Carcinoma through Multitargeted Inhibition of Receptor Tyrosine Kinases |
| title_full | MBP-11901 Inhibits Tumor Growth of Hepatocellular Carcinoma through Multitargeted Inhibition of Receptor Tyrosine Kinases |
| title_fullStr | MBP-11901 Inhibits Tumor Growth of Hepatocellular Carcinoma through Multitargeted Inhibition of Receptor Tyrosine Kinases |
| title_full_unstemmed | MBP-11901 Inhibits Tumor Growth of Hepatocellular Carcinoma through Multitargeted Inhibition of Receptor Tyrosine Kinases |
| title_short | MBP-11901 Inhibits Tumor Growth of Hepatocellular Carcinoma through Multitargeted Inhibition of Receptor Tyrosine Kinases |
| title_sort | mbp 11901 inhibits tumor growth of hepatocellular carcinoma through multitargeted inhibition of receptor tyrosine kinases |
| topic | hepatocellular carcinoma targeted therapy tyrosine kinase inhibitor anticancer agent complete response |
| url | https://www.mdpi.com/2072-6694/14/8/1994 |
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