Bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma. Issue 10 (22nd August 2019)

• Record Type: Journal Article
• Authors: Kasahara, Yoshiya; Endo, Kazuhira; Ueno, Takayoshi; Ueno, Haruna; Moriyama‐Kita, Makiko; Odani, Akira; Yoshizaki, Tomokazu
• Is Part Of: Cancer science. Volume 110:Issue 10(2019)
• Page Start: 3288
• Page End: 3295
• Publication Date: 2019-08-22
• Subjects: bone invasion -- cisplatin -- drug delivery system -- head and neck cancer -- ionic platinum complex; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14145
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: 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. Abstract : Cisplatin (CDDP) is an important drug for chemotherapy. However, its limitations include nephrotoxicity and lack of an effect on bone invasion. We developed anionic CDDP (3Pt) to increase the antitumor effect on bone invasion and reduce toxicity problems. The present study aimed to analyze the cytotoxicity of 3Pt and evaluate its antitumor and nephrotoxic effects.