The cytostatic effects of lovastatin on ACC-MESO-1 cells

Keisuke Asakura, Yotaro Izumi, Michiko Yamamoto, Yoshikane Yamauchi, Kenji Kawai, Akihiko Serizawa, Tomoko Mizushima, Mitsuyo Ohmura, Masafumi Kawamura, Masatoshi Wakui, Takeshi Adachi, Masato Nakamura, Makoto Suematsu, Hiroaki Nomori

Research output: Contribution to journalArticle

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Abstract

Background: Malignant pleural mesothelioma is known to be widely resistant to therapy, and new treatment strategies are needed. Statins are small molecules that suppress the production of multiple hydrophobic substrates in the mevalonate pathway. Although still controversial, statins may decrease the risk of certain cancers such as colon cancer, lung cancer, and prostate cancer. Since the evaluations of the direct effect of statins on malignant mesothelioma are still few, the present study was done to evaluate the effects of lovastatin on ACC-MESO-1 cells in vivo and to investigate the potential mechanisms involved in vitro. Materials and Methods: The in vivo effect of lovastatin was evaluated using an NOD/SCID/γnull (NOG) mouse model of human malignant mesothelioma using ACC-MESO-1 cells. Lovastatin was also applied to ACC-MESO-1 cells in vitro and the effects were observed. Results: Lovastatin administration reduced primary tumor and metastasis in the NOG mouse model of human malignant mesothelioma. In vitro studies showed that lovastatin administration induced cytostatic effects as per reduced cell viability and cell migration in ACC-MESO-1 cells. These effects were suggested to be dependent on autophagic changes rather than apoptosis. Furthermore, induction of autophagic changes by lovastatin in ACC-MESO-1 cells was independent of mTOR, and was considered to be dependent at least in part on Rac/phospholipase C/ inositol 1,4,5-triphosphate axis. Conclusions: These results suggest that it may be possible to utilize statins, or other pharmacological agents that are known to induce mTOR-independent autophagy, as an adjunct to standard treatments in malignant mesothelioma.

Original languageEnglish
JournalJournal of Surgical Research
Volume170
Issue number2
DOIs
Publication statusPublished - 2011 Oct

Fingerprint

Lovastatin
Cytostatic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lung Neoplasms
Prostatic Neoplasms
Mevalonic Acid
Inositol 1,4,5-Trisphosphate
Autophagy
Type C Phospholipases
Colonic Neoplasms
Cell Movement
Neoplasms
Cell Survival
Malignant Mesothelioma
Pharmacology
Apoptosis
Neoplasm Metastasis
In Vitro Techniques

Keywords

  • autophagic changes
  • mesothelioma
  • statins

ASJC Scopus subject areas

  • Surgery

Cite this

Asakura, K., Izumi, Y., Yamamoto, M., Yamauchi, Y., Kawai, K., Serizawa, A., ... Nomori, H. (2011). The cytostatic effects of lovastatin on ACC-MESO-1 cells. Journal of Surgical Research, 170(2). https://doi.org/10.1016/j.jss.2011.06.037

The cytostatic effects of lovastatin on ACC-MESO-1 cells. / Asakura, Keisuke; Izumi, Yotaro; Yamamoto, Michiko; Yamauchi, Yoshikane; Kawai, Kenji; Serizawa, Akihiko; Mizushima, Tomoko; Ohmura, Mitsuyo; Kawamura, Masafumi; Wakui, Masatoshi; Adachi, Takeshi; Nakamura, Masato; Suematsu, Makoto; Nomori, Hiroaki.

In: Journal of Surgical Research, Vol. 170, No. 2, 10.2011.

Research output: Contribution to journalArticle

Asakura, K, Izumi, Y, Yamamoto, M, Yamauchi, Y, Kawai, K, Serizawa, A, Mizushima, T, Ohmura, M, Kawamura, M, Wakui, M, Adachi, T, Nakamura, M, Suematsu, M & Nomori, H 2011, 'The cytostatic effects of lovastatin on ACC-MESO-1 cells', Journal of Surgical Research, vol. 170, no. 2. https://doi.org/10.1016/j.jss.2011.06.037
Asakura, Keisuke ; Izumi, Yotaro ; Yamamoto, Michiko ; Yamauchi, Yoshikane ; Kawai, Kenji ; Serizawa, Akihiko ; Mizushima, Tomoko ; Ohmura, Mitsuyo ; Kawamura, Masafumi ; Wakui, Masatoshi ; Adachi, Takeshi ; Nakamura, Masato ; Suematsu, Makoto ; Nomori, Hiroaki. / The cytostatic effects of lovastatin on ACC-MESO-1 cells. In: Journal of Surgical Research. 2011 ; Vol. 170, No. 2.
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abstract = "Background: Malignant pleural mesothelioma is known to be widely resistant to therapy, and new treatment strategies are needed. Statins are small molecules that suppress the production of multiple hydrophobic substrates in the mevalonate pathway. Although still controversial, statins may decrease the risk of certain cancers such as colon cancer, lung cancer, and prostate cancer. Since the evaluations of the direct effect of statins on malignant mesothelioma are still few, the present study was done to evaluate the effects of lovastatin on ACC-MESO-1 cells in vivo and to investigate the potential mechanisms involved in vitro. Materials and Methods: The in vivo effect of lovastatin was evaluated using an NOD/SCID/γnull (NOG) mouse model of human malignant mesothelioma using ACC-MESO-1 cells. Lovastatin was also applied to ACC-MESO-1 cells in vitro and the effects were observed. Results: Lovastatin administration reduced primary tumor and metastasis in the NOG mouse model of human malignant mesothelioma. In vitro studies showed that lovastatin administration induced cytostatic effects as per reduced cell viability and cell migration in ACC-MESO-1 cells. These effects were suggested to be dependent on autophagic changes rather than apoptosis. Furthermore, induction of autophagic changes by lovastatin in ACC-MESO-1 cells was independent of mTOR, and was considered to be dependent at least in part on Rac/phospholipase C/ inositol 1,4,5-triphosphate axis. Conclusions: These results suggest that it may be possible to utilize statins, or other pharmacological agents that are known to induce mTOR-independent autophagy, as an adjunct to standard treatments in malignant mesothelioma.",
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AU - Kawai, Kenji

AU - Serizawa, Akihiko

AU - Mizushima, Tomoko

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AU - Wakui, Masatoshi

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AU - Suematsu, Makoto

AU - Nomori, Hiroaki

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