New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer

Vincent Chin-Hung Chen^{1

2}, Yi-Hsuan Hsieh^{2

3}, Tzu-Chin Lin⁴, Mong-Liang Lu^{5

6}, Yin-To Liao⁷, Yao-Hsu Yang^{8

9

10}, Tsai-Ching Hsu^{11

12

13}, Robert Stewart^{14

15}, Jun-Cheng Weng^{1

16}, Min-Jing Lee¹, Wei-Che Chiu^{17

18}, Bor-Show Tzang^{11

12

13

19}

Affiliations

¹ Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.
² School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
³ Department of Child Psychiatry, Chang Gung Memorial Hospital at Taoyuan, Taoyuan 33305, Taiwan.
⁴ Bethel Psychiatric Clinic, Taipei 11074, Taiwan.
⁵ Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
⁶ Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan.
⁷ Department of Psychiatry, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
⁸ Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.
⁹ Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.
¹⁰ School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
¹¹ Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
¹² Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan.
¹³ Immunology Research Center, Chung Shan Medical University, Taichung 40201, Taiwan.
¹⁴ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.
¹⁵ South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK.
¹⁶ Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan 33302, Taiwan.
¹⁷ Department of Psychiatry, Cathay General Hospital, Taipei 10686, Taiwan.
¹⁸ School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24257, Taiwan.
¹⁹ Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.

PMID: 32545657
PMCID: PMC7352868
DOI: 10.3390/cancers12061560

New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer

Vincent Chin-Hung Chen et al. Cancers (Basel). 2020.

. 2020 Jun 12;12(6):1560.

doi: 10.3390/cancers12061560.

Authors

Affiliations

¹ Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.
² School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
³ Department of Child Psychiatry, Chang Gung Memorial Hospital at Taoyuan, Taoyuan 33305, Taiwan.
⁴ Bethel Psychiatric Clinic, Taipei 11074, Taiwan.
⁵ Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
⁶ Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan.
⁷ Department of Psychiatry, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
⁸ Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.
⁹ Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.
¹⁰ School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
¹¹ Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
¹² Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan.
¹³ Immunology Research Center, Chung Shan Medical University, Taichung 40201, Taiwan.
¹⁴ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK.
¹⁵ South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK.
¹⁶ Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan 33302, Taiwan.
¹⁷ Department of Psychiatry, Cathay General Hospital, Taipei 10686, Taiwan.
¹⁸ School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24257, Taiwan.
¹⁹ Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.

PMID: 32545657
PMCID: PMC7352868
DOI: 10.3390/cancers12061560

Abstract

Background: The potential of old drugs in novel indications is being greatly valued. We propose a triple-model study involving population-based, cell, and animal studies to investigate the effects of risperidone, a type of second-generation antipsychotic (SGA) drug, on colorectal cancer. Methods: We used data from Taiwan's National Health Insurance Research Database between 1997 and 2013 to compare 101,989 patients with colorectal cancer and 101,989 controls. Conditional logistic regression analyses were used to explore the association between SGA exposure and the risk of colorectal cancer. The following bench studies were performed to evaluate the findings of the population-based study. Results: We found that SGAs had been less commonly used in colorectal cancer patients than in controls. The colorectal cancer risk was reduced with an increase in the cumulative defined daily dose (cDDD) of SGAs. The adjusted odds ratio of antipsychotic use for cDDD days was 0.32 (95% CI: 0.25-0.42). Risperidone exhibited the most prominent tumor inhibition effect in a cell screen study. Bench data revealed that risperidone significantly induced apoptosis and elevated intracellular ROS in human SW480 cells and suppressed the proliferation of the xenografted SW480 tumor in nude mice. Conclusion: This triple-model study demonstrates the association between risperidone usage and a lower risk of colorectal cancer.

Keywords: SW480; Taiwan National Health Insurance; antipsychotics; colorectal cancer; risperidone.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Effects of different antipsychotics on the survival of SW480 cells. “a” indicates a significant difference (p < 0.05) compared with clozapine, flupentixol, quetiapine, or the risperidone control (0 mM), respectively. Similar results were obtained in three to six repeated experiments.

**Figure 2**
Survival of SW480 cells in the presence of risperidone. “a” indicates a significant difference compared with CCD 841CoN (0 mM). “b” indicates a significant difference compared with SW480 (0 mM). “c” indicates a significant difference between CCD 841CoN and SW480. The superscript letters “a,” “b,” and “c” indicate significant differences (p < 0.05). Similar results were obtained in three to six repeated experiments.

**Figure 3**
Sub-G1 proportion of SW480 cells in the presence of risperidone. “a” indicates a significant difference (p < 0.05) compared with the control group. Similar results were obtained in three to six repeated experiments.

**Figure 4**
Apoptosis of SW480 cells in the presence of risperidone. “a” indicates a significant difference (p < 0.05) compared with the control group. Similar results were obtained in three repeated experiments.

**Figure 5**
ROS concentration of SW480 cells in the presence of risperidone. “a” indicates a significant difference (*p <* 0.05) compared with the control group (0 mM). N-acetyl cysteine and antimycin A were used as negative and positive controls, respectively. Similar results were obtained in three repeated experiments.

**Figure 6**
Effects of risperidone on xenografted SW480 cells. “a” indicates a significant difference compared with the control group. “b” indicates a significant difference compared with low-dose risperidone. The superscript letters “a” and “b” indicate significant differences (p < 0.05).

See this image and copyright information in PMC

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New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer

Affiliations

New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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