Autophagy inhibition enhances antiproliferative effect of salinomycin in pancreatic cancer cells

Sho Endo, Kohei Nakata, Akiko Sagara, Kazuhiro Koikawa, Yohei Ando, Shin Kibe, Shin Takesue, Hiromichi Nakayama, Toshiya Abe, Takashi Okumura, Taiki Moriyama, Yoshihiro Miyasaka, Kenoki Ohuchida, Takao Ohtsuka, Kazuhiro Mizumoto, Masafumi Nakamura

Research output: Contribution to journalArticle

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Abstract

Background Salinomycin has cytotoxic effects on various types of malignancy and induces autophagy. However, it has not been clarified whether autophagy induced by salinomycin treatment has a protective or cytotoxic role. We investigated whether salinomycin affects autophagy in pancreatic cancer cells and whether autophagy induced by salinomycin treatment has a protective or cytotoxic role in these cells. Methods We investigated the effect of salinomycin using three pancreatic cancer cell lines. We investigated effect on proliferation and the CD133 positive fraction using flow cytometry. In addition, we monitored the change in autophagic activity after salinomycin treatment using fluorescent immunostaining, western blotting, and flow cytometry. Finally, knockdown of ATG5 or ATG7 by siRNA was used to investigate the impact of autophagy inhibition on sensitivity to salinomycin. Results Salinomycin suppressed the proliferation of pancreatic cancer cells in a concentration dependent manner, and reduced the CD133 positive fraction. Salinomycin enhanced autophagy activity in these cells in a concentration dependent manner. Autophagy inhibition made pancreatic cancer cells more sensitive to salinomycin. Conclusions Our data provide the first evidence indicating that autophagy induced by salinomycin have a protective role in pancreatic cancer cells. A new therapeutic strategy of combining salinomycin, autophagy inhibitors, and anticancer drugs could hold promise for pancreatic cancer treatment.

Original languageEnglish
Pages (from-to)990-996
Number of pages7
JournalPancreatology
Volume17
Issue number6
DOIs
Publication statusPublished - Nov 2017

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Autophagy
Pancreatic Neoplasms
salinomycin
Flow Cytometry
Small Interfering RNA
Western Blotting

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Gastroenterology

Cite this

Autophagy inhibition enhances antiproliferative effect of salinomycin in pancreatic cancer cells. / Endo, Sho; Nakata, Kohei; Sagara, Akiko; Koikawa, Kazuhiro; Ando, Yohei; Kibe, Shin; Takesue, Shin; Nakayama, Hiromichi; Abe, Toshiya; Okumura, Takashi; Moriyama, Taiki; Miyasaka, Yoshihiro; Ohuchida, Kenoki; Ohtsuka, Takao; Mizumoto, Kazuhiro; Nakamura, Masafumi.

In: Pancreatology, Vol. 17, No. 6, 11.2017, p. 990-996.

Research output: Contribution to journalArticle

Endo, Sho ; Nakata, Kohei ; Sagara, Akiko ; Koikawa, Kazuhiro ; Ando, Yohei ; Kibe, Shin ; Takesue, Shin ; Nakayama, Hiromichi ; Abe, Toshiya ; Okumura, Takashi ; Moriyama, Taiki ; Miyasaka, Yoshihiro ; Ohuchida, Kenoki ; Ohtsuka, Takao ; Mizumoto, Kazuhiro ; Nakamura, Masafumi. / Autophagy inhibition enhances antiproliferative effect of salinomycin in pancreatic cancer cells. In: Pancreatology. 2017 ; Vol. 17, No. 6. pp. 990-996.
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T1 - Autophagy inhibition enhances antiproliferative effect of salinomycin in pancreatic cancer cells

AU - Endo, Sho

AU - Nakata, Kohei

AU - Sagara, Akiko

AU - Koikawa, Kazuhiro

AU - Ando, Yohei

AU - Kibe, Shin

AU - Takesue, Shin

AU - Nakayama, Hiromichi

AU - Abe, Toshiya

AU - Okumura, Takashi

AU - Moriyama, Taiki

AU - Miyasaka, Yoshihiro

AU - Ohuchida, Kenoki

AU - Ohtsuka, Takao

AU - Mizumoto, Kazuhiro

AU - Nakamura, Masafumi

PY - 2017/11

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N2 - Background Salinomycin has cytotoxic effects on various types of malignancy and induces autophagy. However, it has not been clarified whether autophagy induced by salinomycin treatment has a protective or cytotoxic role. We investigated whether salinomycin affects autophagy in pancreatic cancer cells and whether autophagy induced by salinomycin treatment has a protective or cytotoxic role in these cells. Methods We investigated the effect of salinomycin using three pancreatic cancer cell lines. We investigated effect on proliferation and the CD133 positive fraction using flow cytometry. In addition, we monitored the change in autophagic activity after salinomycin treatment using fluorescent immunostaining, western blotting, and flow cytometry. Finally, knockdown of ATG5 or ATG7 by siRNA was used to investigate the impact of autophagy inhibition on sensitivity to salinomycin. Results Salinomycin suppressed the proliferation of pancreatic cancer cells in a concentration dependent manner, and reduced the CD133 positive fraction. Salinomycin enhanced autophagy activity in these cells in a concentration dependent manner. Autophagy inhibition made pancreatic cancer cells more sensitive to salinomycin. Conclusions Our data provide the first evidence indicating that autophagy induced by salinomycin have a protective role in pancreatic cancer cells. A new therapeutic strategy of combining salinomycin, autophagy inhibitors, and anticancer drugs could hold promise for pancreatic cancer treatment.

AB - Background Salinomycin has cytotoxic effects on various types of malignancy and induces autophagy. However, it has not been clarified whether autophagy induced by salinomycin treatment has a protective or cytotoxic role. We investigated whether salinomycin affects autophagy in pancreatic cancer cells and whether autophagy induced by salinomycin treatment has a protective or cytotoxic role in these cells. Methods We investigated the effect of salinomycin using three pancreatic cancer cell lines. We investigated effect on proliferation and the CD133 positive fraction using flow cytometry. In addition, we monitored the change in autophagic activity after salinomycin treatment using fluorescent immunostaining, western blotting, and flow cytometry. Finally, knockdown of ATG5 or ATG7 by siRNA was used to investigate the impact of autophagy inhibition on sensitivity to salinomycin. Results Salinomycin suppressed the proliferation of pancreatic cancer cells in a concentration dependent manner, and reduced the CD133 positive fraction. Salinomycin enhanced autophagy activity in these cells in a concentration dependent manner. Autophagy inhibition made pancreatic cancer cells more sensitive to salinomycin. Conclusions Our data provide the first evidence indicating that autophagy induced by salinomycin have a protective role in pancreatic cancer cells. A new therapeutic strategy of combining salinomycin, autophagy inhibitors, and anticancer drugs could hold promise for pancreatic cancer treatment.

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