Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma

Shoji Ryumon, Tatsuo Okui, Yuki Kunisada, Koji Kishimoto, Tsuyoshi Shimo, Kazuaki Hasegawa, Soichiro Ibaragi, Kentaro Akiyama, Nguyen Thi Thu Ha, Nur Mohammad Monsur Hassan, Akira Sasaki

Research output: Contribution to journalArticle

Abstract

Platinum-based antitumor agents have been widely used to treat head and neck squamous cell carcinoma (HNSCC) and numerous other malignancies. Cisplatin is the most frequently used platinum-based antitumor agent, however drug resistance and numerous undesirable side effects limit its clinical efficacy for cancer patients. Cancer cells discharge cisplatin into the extracellular space via copper transporters such as ATPase copper transporting beta (ATP7B) in order to escape from cisplatin-induced cell death. In the present study, it was demonstrated for the first time that the copper chelator ammonium tetrathiomolybdate (TM) has several promising effects on cisplatin and HNSCC. First, TM suppressed the ATP7B expression in HNSCC cell lines in vitro, thereby enhancing the accumulation and apoptotic effect of cisplatin in the cancer cells. Next, it was revealed that TM enhanced the antitumor effect of cisplatin in HNSCC cell tumor progression in a mouse model of bone invasion, which is important since HNSCC cells frequently invade to facial bone. Finally, it was demonstrated that TM was able to overcome the cisplatin resistance of a human cancer cell line, A431, via ATP7B depression in vitro.

Original languageEnglish
Pages (from-to)2611-2621
Number of pages11
JournalOncology Reports
Volume42
Issue number6
Early online dateOct 2019
DOIs
Publication statusPublished - Dec 2019

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Cisplatin
Neoplasms
Platinum
Antineoplastic Agents
Copper
Facial Bones
Cell Line
Extracellular Space
Chelating Agents
copper-transporting ATPases
Carcinoma, squamous cell of head and neck
tetrathiomolybdate
Drug Resistance
Cell Death
Bone and Bones

Cite this

Ryumon, Shoji ; Okui, Tatsuo ; Kunisada, Yuki ; Kishimoto, Koji ; Shimo, Tsuyoshi ; Hasegawa, Kazuaki ; Ibaragi, Soichiro ; Akiyama, Kentaro ; Ha, Nguyen Thi Thu ; Hassan, Nur Mohammad Monsur ; Sasaki, Akira. / Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma. In: Oncology Reports. 2019 ; Vol. 42, No. 6. pp. 2611-2621.
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abstract = "Platinum-based antitumor agents have been widely used to treat head and neck squamous cell carcinoma (HNSCC) and numerous other malignancies. Cisplatin is the most frequently used platinum-based antitumor agent, however drug resistance and numerous undesirable side effects limit its clinical efficacy for cancer patients. Cancer cells discharge cisplatin into the extracellular space via copper transporters such as ATPase copper transporting beta (ATP7B) in order to escape from cisplatin-induced cell death. In the present study, it was demonstrated for the first time that the copper chelator ammonium tetrathiomolybdate (TM) has several promising effects on cisplatin and HNSCC. First, TM suppressed the ATP7B expression in HNSCC cell lines in vitro, thereby enhancing the accumulation and apoptotic effect of cisplatin in the cancer cells. Next, it was revealed that TM enhanced the antitumor effect of cisplatin in HNSCC cell tumor progression in a mouse model of bone invasion, which is important since HNSCC cells frequently invade to facial bone. Finally, it was demonstrated that TM was able to overcome the cisplatin resistance of a human cancer cell line, A431, via ATP7B depression in vitro.",
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Ryumon, S, Okui, T, Kunisada, Y, Kishimoto, K, Shimo, T, Hasegawa, K, Ibaragi, S, Akiyama, K, Ha, NTT, Hassan, NMM & Sasaki, A 2019, 'Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma', Oncology Reports, vol. 42, no. 6, pp. 2611-2621. https://doi.org/10.3892/or.2019.7367

Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma. / Ryumon, Shoji; Okui, Tatsuo; Kunisada, Yuki; Kishimoto, Koji; Shimo, Tsuyoshi; Hasegawa, Kazuaki; Ibaragi, Soichiro; Akiyama, Kentaro; Ha, Nguyen Thi Thu; Hassan, Nur Mohammad Monsur; Sasaki, Akira.

In: Oncology Reports, Vol. 42, No. 6, 12.2019, p. 2611-2621.

Research output: Contribution to journalArticle

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T1 - Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma

AU - Ryumon, Shoji

AU - Okui, Tatsuo

AU - Kunisada, Yuki

AU - Kishimoto, Koji

AU - Shimo, Tsuyoshi

AU - Hasegawa, Kazuaki

AU - Ibaragi, Soichiro

AU - Akiyama, Kentaro

AU - Ha, Nguyen Thi Thu

AU - Hassan, Nur Mohammad Monsur

AU - Sasaki, Akira

PY - 2019/12

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N2 - Platinum-based antitumor agents have been widely used to treat head and neck squamous cell carcinoma (HNSCC) and numerous other malignancies. Cisplatin is the most frequently used platinum-based antitumor agent, however drug resistance and numerous undesirable side effects limit its clinical efficacy for cancer patients. Cancer cells discharge cisplatin into the extracellular space via copper transporters such as ATPase copper transporting beta (ATP7B) in order to escape from cisplatin-induced cell death. In the present study, it was demonstrated for the first time that the copper chelator ammonium tetrathiomolybdate (TM) has several promising effects on cisplatin and HNSCC. First, TM suppressed the ATP7B expression in HNSCC cell lines in vitro, thereby enhancing the accumulation and apoptotic effect of cisplatin in the cancer cells. Next, it was revealed that TM enhanced the antitumor effect of cisplatin in HNSCC cell tumor progression in a mouse model of bone invasion, which is important since HNSCC cells frequently invade to facial bone. Finally, it was demonstrated that TM was able to overcome the cisplatin resistance of a human cancer cell line, A431, via ATP7B depression in vitro.

AB - Platinum-based antitumor agents have been widely used to treat head and neck squamous cell carcinoma (HNSCC) and numerous other malignancies. Cisplatin is the most frequently used platinum-based antitumor agent, however drug resistance and numerous undesirable side effects limit its clinical efficacy for cancer patients. Cancer cells discharge cisplatin into the extracellular space via copper transporters such as ATPase copper transporting beta (ATP7B) in order to escape from cisplatin-induced cell death. In the present study, it was demonstrated for the first time that the copper chelator ammonium tetrathiomolybdate (TM) has several promising effects on cisplatin and HNSCC. First, TM suppressed the ATP7B expression in HNSCC cell lines in vitro, thereby enhancing the accumulation and apoptotic effect of cisplatin in the cancer cells. Next, it was revealed that TM enhanced the antitumor effect of cisplatin in HNSCC cell tumor progression in a mouse model of bone invasion, which is important since HNSCC cells frequently invade to facial bone. Finally, it was demonstrated that TM was able to overcome the cisplatin resistance of a human cancer cell line, A431, via ATP7B depression in vitro.

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