Chloroquine Inhibition of Autophagy Enhanced the Anticancer Effects of <i>Listeria monocytogenes</i> in Melanoma
<i>Listeria monocytogenes</i> has been shown to exhibit antitumor effects. However, the mechanism remains unclear. Autophagy is a cellular catabolic process that mediates the degradation of unfolded proteins and damaged organelles in the cytosol, which is a double-edged sword in tumorige...
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MDPI AG
2023-02-01
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| author | Zuhua Yu Yingying Zhao Ke Ding Lei He Chengshui Liao Jing Li Songbiao Chen Ke Shang Jian Chen Chuan Yu Chunjie Zhang Yinju Li Shaohui Wang Yanyan Jia |
| author_facet | Zuhua Yu Yingying Zhao Ke Ding Lei He Chengshui Liao Jing Li Songbiao Chen Ke Shang Jian Chen Chuan Yu Chunjie Zhang Yinju Li Shaohui Wang Yanyan Jia |
| author_sort | Zuhua Yu |
| collection | DOAJ |
| description | <i>Listeria monocytogenes</i> has been shown to exhibit antitumor effects. However, the mechanism remains unclear. Autophagy is a cellular catabolic process that mediates the degradation of unfolded proteins and damaged organelles in the cytosol, which is a double-edged sword in tumorigenesis and treatment outcome. Tumor cells display lower levels of basal autophagic activity than normal cells. This study examined the role and molecular mechanism of autophagy in the antitumor effects induced by LM, as well as the combined antitumor effect of LM and the autophagy inhibitor chloroquine (CQ). We investigated LM-induced autophagy in B16F10 melanoma cells by real-time PCR, immunofluorescence, Western blotting, and transmission electron microscopy and found that autophagic markers were increased following the infection of tumor cells with LM. The autophagy pathway in B16F10 cells was blocked with the pharmacological autophagy inhibitor chloroquine, which led to a significant increase in intracellular bacterial multiplication in tumor cells. The combination of CQ and LM enhanced LM-mediated cancer cell death and apoptosis compared with LM infection alone. Furthermore, the combination of LM and CQ significantly inhibited tumor growth and prolonged the survival time of mice in vivo, which was associated with the increased colonization and accumulation of LM and induced more cell apoptosis in primary tumors. The data indicated that the inhibition of autophagy by CQ enhanced LM-mediated antitumor activity in vitro and in vivo and provided a novel strategy to improving the anticancer efficacy of bacterial treatment. |
| first_indexed | 2024-03-11T08:23:40Z |
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| id | doaj.art-eeec1385c05c4ab89b8e27f8db61f54f |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-11T08:23:40Z |
| publishDate | 2023-02-01 |
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| series | Microorganisms |
| spelling | doaj.art-eeec1385c05c4ab89b8e27f8db61f54f2023-11-16T22:15:26ZengMDPI AGMicroorganisms2076-26072023-02-0111240810.3390/microorganisms11020408Chloroquine Inhibition of Autophagy Enhanced the Anticancer Effects of <i>Listeria monocytogenes</i> in MelanomaZuhua Yu0Yingying Zhao1Ke Ding2Lei He3Chengshui Liao4Jing Li5Songbiao Chen6Ke Shang7Jian Chen8Chuan Yu9Chunjie Zhang10Yinju Li11Shaohui Wang12Yanyan Jia13Luoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, ChinaShanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, ChinaLuoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, China<i>Listeria monocytogenes</i> has been shown to exhibit antitumor effects. However, the mechanism remains unclear. Autophagy is a cellular catabolic process that mediates the degradation of unfolded proteins and damaged organelles in the cytosol, which is a double-edged sword in tumorigenesis and treatment outcome. Tumor cells display lower levels of basal autophagic activity than normal cells. This study examined the role and molecular mechanism of autophagy in the antitumor effects induced by LM, as well as the combined antitumor effect of LM and the autophagy inhibitor chloroquine (CQ). We investigated LM-induced autophagy in B16F10 melanoma cells by real-time PCR, immunofluorescence, Western blotting, and transmission electron microscopy and found that autophagic markers were increased following the infection of tumor cells with LM. The autophagy pathway in B16F10 cells was blocked with the pharmacological autophagy inhibitor chloroquine, which led to a significant increase in intracellular bacterial multiplication in tumor cells. The combination of CQ and LM enhanced LM-mediated cancer cell death and apoptosis compared with LM infection alone. Furthermore, the combination of LM and CQ significantly inhibited tumor growth and prolonged the survival time of mice in vivo, which was associated with the increased colonization and accumulation of LM and induced more cell apoptosis in primary tumors. The data indicated that the inhibition of autophagy by CQ enhanced LM-mediated antitumor activity in vitro and in vivo and provided a novel strategy to improving the anticancer efficacy of bacterial treatment.https://www.mdpi.com/2076-2607/11/2/408<i>Listeria monocytogenes</i>autophagychloroquineantitumormelanoma |
| spellingShingle | Zuhua Yu Yingying Zhao Ke Ding Lei He Chengshui Liao Jing Li Songbiao Chen Ke Shang Jian Chen Chuan Yu Chunjie Zhang Yinju Li Shaohui Wang Yanyan Jia Chloroquine Inhibition of Autophagy Enhanced the Anticancer Effects of <i>Listeria monocytogenes</i> in Melanoma Microorganisms <i>Listeria monocytogenes</i> autophagy chloroquine antitumor melanoma |
| title | Chloroquine Inhibition of Autophagy Enhanced the Anticancer Effects of <i>Listeria monocytogenes</i> in Melanoma |
| title_full | Chloroquine Inhibition of Autophagy Enhanced the Anticancer Effects of <i>Listeria monocytogenes</i> in Melanoma |
| title_fullStr | Chloroquine Inhibition of Autophagy Enhanced the Anticancer Effects of <i>Listeria monocytogenes</i> in Melanoma |
| title_full_unstemmed | Chloroquine Inhibition of Autophagy Enhanced the Anticancer Effects of <i>Listeria monocytogenes</i> in Melanoma |
| title_short | Chloroquine Inhibition of Autophagy Enhanced the Anticancer Effects of <i>Listeria monocytogenes</i> in Melanoma |
| title_sort | chloroquine inhibition of autophagy enhanced the anticancer effects of i listeria monocytogenes i in melanoma |
| topic | <i>Listeria monocytogenes</i> autophagy chloroquine antitumor melanoma |
| url | https://www.mdpi.com/2076-2607/11/2/408 |
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