title: Inhibition of autophagy by chloroquine induces apoptosis in primary effusion lymphoma in vitro and in vivo through induction of endoplasmic reticulum stress.
abstract: Autophagy plays a crucial role in cancer cell survival and the inhibition of autophagy is attracting attention as an emerging strategy for the treatment of cancer. Chloroquine (CQ) is an anti-malarial drug, and is also known as an inhibitor of autophagy. Recently, it has been found that CQ induces cancer cell death through the inhibition of autophagy; however, the underlying mechanism is not entirely understood. In this study, we identified the role of CQ-induced cancer cell death using Primary Effusion Lymphoma (PEL) cells. We found that a CQ treatment induced caspase-dependent apoptosis in vitro. CQ also suppressed PEL cell growth in a PEL xenograft mouse model. We showed that CQ activated endoplasmic reticulum (ER) stress signal pathways and induced CHOP, which is an inducer of apoptosis. CQ-induced cell death was significantly decreased by salbrinal, an ER stress inhibitor, indicating that CQ-induced apoptosis in PEL cells depended on ER stress. We show here for the first time that the inhibition of autophagy induces ER stress-mediated apoptosis in PEL cells. Thus, the inhibition of autophagy is a novel strategy for cancer chemotherapy.
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1, Honjo, Kumamoto, 860-0811, Japan.
authors.forename: Md
authors.initials: M
authors.lastname: Masud Alam
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1, Honjo, Kumamoto, 860-0811, Japan.
authors.forename: Ryusho
authors.initials: R
authors.lastname: Kariya
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1, Honjo, Kumamoto, 860-0811, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1, Honjo, Kumamoto, 860-0811, Japan.
authors.forename: Kouki
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1, Honjo, Kumamoto, 860-0811, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Kudo
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1, Honjo, Kumamoto, 860-0811, Japan. okadas@kumamoto-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002738:Chloroquine / Q000008:administration & dosage*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D006801:Humans; D054685:Lymphoma, Primary Effusion / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D008819:Mice, Nude
chemical_list: D000970:Antineoplastic Agents; D002738:Chloroquine
keywords: Apoptosis; Autophagy; Chloroquine (CQ); Endoplasmic Reticulum (ER) stress; Mouse model; Primary Effusion Lymphoma (PEL)