Galectin-9 Induces Mitochondria-Mediated Apoptosis of Esophageal Cancer In Vitro and In Vivo in a Xenograft Mouse Model

Chiyo, Taiga; Fujita, Koji; Iwama, Hisakazu; Fujihara, Shintaro; Tadokoro, Tomoko; Ohura, Kyoko; Matsui, Takanori; Goda, Yasuhiro; Kobayashi, Nobuya; Nishiyama, Noriko; Yachida, Tatsuo; Morishita, Asahiro; Kobara, Hideki; Mori, Hirohito; Niki, Toshiro; Hirashima, Mitsuomi; Himoto, Takashi; Masaki, Tsutomu

doi:10.3390/ijms20112634

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Galectin-9 Induces Mitochondria-Mediated Apoptosis of Esophageal Cancer In Vitro and In Vivo in a Xenograft Mouse Model

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Department of Gastroenterology and Neurology, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan

Life Science Research Center, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan

Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan

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Department of Medical Technology, Kagawa Prefectural University of Health Sciences, 281-1, Hara, Mure-Cho, Takamatsu, Kagawa 761-0123, Japan

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2019, 20(11), 2634; https://doi.org/10.3390/ijms20112634

Received: 24 April 2019 / Revised: 20 May 2019 / Accepted: 24 May 2019 / Published: 29 May 2019

(This article belongs to the Special Issue Galectins in Cancer and Translational Research 2.0)

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Abstract

Galectin-9 (Gal-9) enhances tumor immunity mediated by T cells, macrophages, and dendritic cells. Its expression level in various cancers correlates with prognosis. Furthermore, Gal-9 directly induces apoptosis in various cancers; however, its mechanism of action and bioactivity has not been clarified. We evaluated Gal-9 antitumor effect against esophageal squamous cell carcinoma (ESCC) to analyze the dynamics of apoptosis-related molecules, elucidate its mechanism of action, and identify relevant changes in miRNA expressions. KYSE-150 and KYSE-180 cells were treated with Gal-9 and their proliferation was evaluated. Gal-9 inhibited cell proliferation in a concentration-dependent manner. The xenograft mouse model established with KYSE-150 cells was administered with Gal-9 and significant suppression in the tumor growth observed. Gal-9 treatment of KYSE-150 cells increased the number of Annexin V-positive cells, activation of caspase-3, and collapse of mitochondrial potential, indicating apoptosis induction. c-Jun NH₂-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) phosphorylation were activated and could be involved in apoptosis. Therefore, Gal-9 induces mitochondria-mediated apoptosis of ESCC and inhibits cell proliferation in vitro and in vivo with JNK and p38 activation. View Full-Text

Keywords: galectin-9; apoptosis; esophageal squamous cell carcinoma; JNK; microRNA

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Chiyo, T.; Fujita, K.; Iwama, H.; Fujihara, S.; Tadokoro, T.; Ohura, K.; Matsui, T.; Goda, Y.; Kobayashi, N.; Nishiyama, N.; Yachida, T.; Morishita, A.; Kobara, H.; Mori, H.; Niki, T.; Hirashima, M.; Himoto, T.; Masaki, T. Galectin-9 Induces Mitochondria-Mediated Apoptosis of Esophageal Cancer In Vitro and In Vivo in a Xenograft Mouse Model. Int. J. Mol. Sci. 2019, 20, 2634. https://doi.org/10.3390/ijms20112634

AMA Style

Chiyo T, Fujita K, Iwama H, Fujihara S, Tadokoro T, Ohura K, Matsui T, Goda Y, Kobayashi N, Nishiyama N, Yachida T, Morishita A, Kobara H, Mori H, Niki T, Hirashima M, Himoto T, Masaki T. Galectin-9 Induces Mitochondria-Mediated Apoptosis of Esophageal Cancer In Vitro and In Vivo in a Xenograft Mouse Model. International Journal of Molecular Sciences. 2019; 20(11):2634. https://doi.org/10.3390/ijms20112634

Chicago/Turabian Style

Chiyo, Taiga, Koji Fujita, Hisakazu Iwama, Shintaro Fujihara, Tomoko Tadokoro, Kyoko Ohura, Takanori Matsui, Yasuhiro Goda, Nobuya Kobayashi, Noriko Nishiyama, Tatsuo Yachida, Asahiro Morishita, Hideki Kobara, Hirohito Mori, Toshiro Niki, Mitsuomi Hirashima, Takashi Himoto, and Tsutomu Masaki. 2019. "Galectin-9 Induces Mitochondria-Mediated Apoptosis of Esophageal Cancer In Vitro and In Vivo in a Xenograft Mouse Model" International Journal of Molecular Sciences 20, no. 11: 2634. https://doi.org/10.3390/ijms20112634

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Galectin-9 Induces Mitochondria-Mediated Apoptosis of Esophageal Cancer In Vitro and In Vivo in a Xenograft Mouse Model

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