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Bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma

Cisplatin (CDDP) is an important drug for chemotherapy in patients with head and neck squamous cell carcinoma. Nephrotoxicity and lack of an effect on bone invasion are limitations of CDDP. To increase its antitumor effect on bone invasion and reduce toxicity problems, anionic Pt complex (3Pt) has b...

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Autores principales: Kasahara, Yoshiya, Endo, Kazuhira, Ueno, Takayoshi, Ueno, Haruna, Moriyama‐Kita, Makiko, Odani, Akira, Yoshizaki, Tomokazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778662/
https://www.ncbi.nlm.nih.gov/pubmed/31348586
http://dx.doi.org/10.1111/cas.14145
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author Kasahara, Yoshiya
Endo, Kazuhira
Ueno, Takayoshi
Ueno, Haruna
Moriyama‐Kita, Makiko
Odani, Akira
Yoshizaki, Tomokazu
author_facet Kasahara, Yoshiya
Endo, Kazuhira
Ueno, Takayoshi
Ueno, Haruna
Moriyama‐Kita, Makiko
Odani, Akira
Yoshizaki, Tomokazu
author_sort Kasahara, Yoshiya
collection PubMed
description Cisplatin (CDDP) is an important drug for chemotherapy in patients with head and neck squamous cell carcinoma. Nephrotoxicity and lack of an effect on bone invasion are limitations of CDDP. To increase its antitumor effect on bone invasion and reduce toxicity problems, anionic Pt complex (3Pt) has been developed. The present study aimed to characterize the basis of the cytotoxicity of the novel platinum complex 3Pt in comparison with that of CDDP for oral squamous cell carcinoma. The ionic platinum complex was prepared to increase solubility and avoid platinum nephrotoxicity. Furthermore, 3Pt was designed to target bone hydroxyapatite and has germinal bisphosphonate moieties for drug delivery. In vitro antitumor activity was assayed in two oral squamous cell carcinoma cell lines. To investigate the antitumor and nephrotoxic effects of 3Pt, nude mice with OSC‐19 were given 3Pt and CDDP. The in vitro growth‐inhibitory effect of 3Pt was significantly less than that of CDDP. However, both 3Pt and CDDP showed equivalent antitumor effects in vivo. Mice injected with CDDP developed renal cell apoptosis; however, those injected with 3Pt were almost free of renal cell injury. In addition to similar in vivo antitumor effects, 3Pt decreased the volume of bone resorption compared to that with CDDP in a bone invasion model using OSC‐19. In conclusion, considering the potential advantages in terms of noticeable antitumor activity on bone invasion and reduced nephrotoxicity, 3Pt represents a significant improvement in the development of bone‐targeting platinum drugs.
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spelling pubmed-67786622019-10-11 Bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma Kasahara, Yoshiya Endo, Kazuhira Ueno, Takayoshi Ueno, Haruna Moriyama‐Kita, Makiko Odani, Akira Yoshizaki, Tomokazu Cancer Sci Original Articles Cisplatin (CDDP) is an important drug for chemotherapy in patients with head and neck squamous cell carcinoma. Nephrotoxicity and lack of an effect on bone invasion are limitations of CDDP. To increase its antitumor effect on bone invasion and reduce toxicity problems, anionic Pt complex (3Pt) has been developed. The present study aimed to characterize the basis of the cytotoxicity of the novel platinum complex 3Pt in comparison with that of CDDP for oral squamous cell carcinoma. The ionic platinum complex was prepared to increase solubility and avoid platinum nephrotoxicity. Furthermore, 3Pt was designed to target bone hydroxyapatite and has germinal bisphosphonate moieties for drug delivery. In vitro antitumor activity was assayed in two oral squamous cell carcinoma cell lines. To investigate the antitumor and nephrotoxic effects of 3Pt, nude mice with OSC‐19 were given 3Pt and CDDP. The in vitro growth‐inhibitory effect of 3Pt was significantly less than that of CDDP. However, both 3Pt and CDDP showed equivalent antitumor effects in vivo. Mice injected with CDDP developed renal cell apoptosis; however, those injected with 3Pt were almost free of renal cell injury. In addition to similar in vivo antitumor effects, 3Pt decreased the volume of bone resorption compared to that with CDDP in a bone invasion model using OSC‐19. In conclusion, considering the potential advantages in terms of noticeable antitumor activity on bone invasion and reduced nephrotoxicity, 3Pt represents a significant improvement in the development of bone‐targeting platinum drugs. John Wiley and Sons Inc. 2019-08-22 2019-10 /pmc/articles/PMC6778662/ /pubmed/31348586 http://dx.doi.org/10.1111/cas.14145 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Kasahara, Yoshiya
Endo, Kazuhira
Ueno, Takayoshi
Ueno, Haruna
Moriyama‐Kita, Makiko
Odani, Akira
Yoshizaki, Tomokazu
Bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma
title Bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma
title_full Bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma
title_fullStr Bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma
title_full_unstemmed Bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma
title_short Bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma
title_sort bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3pt) for oral squamous cell carcinoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778662/
https://www.ncbi.nlm.nih.gov/pubmed/31348586
http://dx.doi.org/10.1111/cas.14145
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