Repurposing the antipsychotic drug penfluridol for cancer treatment (Review)
- Authors:
- Asma Ali Ibrahim Mze
- Amirah Abdul Rahman
-
Affiliations: Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Sungai Buloh, Sungai Buloh, Selangor 47000, Malaysia - Published online on: October 25, 2024 https://doi.org/10.3892/or.2024.8833
- Article Number: 174
-
Copyright: © Ali Ibrahim Mze et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
 |
 |
|
Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A and Bray F: Cancer statistics for the year 2020: An overview. Int J Cancer. Apr 5–2021.(Epub ahead of print). View Article : Google Scholar | |
|
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
World Health Organization (WHO), . Cancer. WHO; Geneva: 2022 | |
|
Chen S, Cao Z, Prettner K, Kuhn M, Yang J, Jiao L, Wang Z, Li W, Geldsetzer P, Bärnighausen T, et al: Estimates and projections of the global economic cost of 29 cancers in 204 countries and territories from 2020 to 2050. JAMA Oncol. 9:465–472. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Gordon N, Stemmer SM, Greenberg D and Goldstein DA: Trajectories of injectable cancer drug costs after launch in the United States. J Clin Oncol. 36:319–325. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Hendouei N, Saghafi F, Shadfar F and Hosseinimehr SJ: Molecular mechanisms of anti-psychotic drugs for improvement of cancer treatment. Eur J Pharmacol. 856:1724022019. View Article : Google Scholar : PubMed/NCBI | |
|
Qu LG, Brand NR, Chao A and Ilbawi AM: Interventions addressing barriers to delayed cancer diagnosis in low- and middle-income countries: A systematic review. Oncologist. 25:e1382–e1395. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Masuda T, Tsuruda Y, Matsumoto Y, Uchida H, Nakayama KI and Mimori K: Drug repositioning in cancer: The current situation in Japan. Cancer Sci. 111:1039–1046. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Wouters OJ, McKee M and Luyten J: Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009–2018. JAMA. 323:844–853. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Low ZY, Farouk IA and Lal SK: Drug Repositioning: New approaches and future prospects for life-debilitating diseases and the COVID-19 pandemic outbreak. Viruses. 12:10582020. View Article : Google Scholar : PubMed/NCBI | |
|
Brown JS: Treatment of cancer with antipsychotic medications: Pushing the boundaries of schizophrenia and cancer. Neurosci Biobehav Rev. 141:1048092022. View Article : Google Scholar : PubMed/NCBI | |
|
Vlachos N, Lampros M, Voulgaris S and Alexiou GA: Repurposing antipsychotics for cancer treatment. Biomedicines. 9:17852021. View Article : Google Scholar : PubMed/NCBI | |
|
Shaw V, Srivastava S and Srivastava SK: Repurposing antipsychotics of the diphenylbutylpiperidine class for cancer therapy. Semin Cancer Biol. 68:75–83. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Varalda M, Antona A, Bettio V, Vachamaram A, Yellenki V, Massarotti A, Baldanzi G and Capello D: Psychotropic drugs show anticancer activity by disrupting mitochondrial and lysosomal function. Front Oncol. 10:5621962020. View Article : Google Scholar : PubMed/NCBI | |
|
Soares BG and Lima MS: Penfluridol for schizophrenia. Cochrane Database Syst Rev. 2006:CD0029232006.PubMed/NCBI | |
|
Chokhawala K and Lee S: Antipsychotic medications. StatPearls [Internet]. StatPearls Publishing; Treasure Island, FL: 2023 | |
|
Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D, Moher D, Peters MDJ, Horsley T, Weeks L, et al: PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 169:467–473. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Mak S and Thomas A: Steps for conducting a scoping review. J Grad Med Educ. 14:565–567. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Arksey H and O'Malley L: Scoping studies: Towards a methodological framework. Int J Soc Res Methodol. 8:19–32. 2005. View Article : Google Scholar | |
|
Hedrick E, Li XX and Safe S: Penfluridol represses integrin expression in breast cancer through induction of reactive oxygen species and downregulation of Sp transcription factors. Mol Cancer Ther. 16:205–216. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Gupta N, Gupta P and Srivastava S: Penfluridol overcomes paclitaxel resistance in metastatic breast cancer. Sci Rep. 9:50662019. View Article : Google Scholar : PubMed/NCBI | |
|
Ranjan A, Gupta P and Srivastava SK: Penfluridol: An antipsychotic agent suppresses metastatic tumor growth in triple-negative breast cancer by inhibiting integrin signaling axis. Cancer Res. 76:877–890. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Srivastava S, Zahra FT, Gupta N, Tullar PE, Srivastava SK and Mikelis CM: Low Dose of Penfluridol Inhibits VEGF-Induced Angiogenesis. Int J Mol Sci. 21:7552020. View Article : Google Scholar : PubMed/NCBI | |
|
Lai TC, Lee YL, Lee WJ, Hung WY, Cheng GZ, Chen JQ, Hsiao M, Chien MH and Chang JH: Synergistic tumor inhibition via energy elimination by repurposing penfluridol and 2-Deoxy-D-Glucose in lung cancer. Cancers (Basel). 14:27502022. View Article : Google Scholar : PubMed/NCBI | |
|
Hung WY, Chang JH, Cheng Y, Cheng GZ, Huang HC, Hsiao M, Chung CL, Lee WJ and Chien MH: Autophagosome accumulation-mediated ATP energy deprivation induced by penfluridol triggers nonapoptotic cell death of lung cancer via activating unfolded protein response. Cell Death Dis. 10:5382019. View Article : Google Scholar : PubMed/NCBI | |
|
Xue Q, Liu Z, Feng Z, Xu Y, Zuo W, Wang Q, Gao T, Zeng J, Hu X, Jia F, et al: Penfluridol: An antipsychotic agent suppresses lung cancer cell growth and metastasis by inducing G0/G1 arrest and apoptosis. Biomed Pharmacother. 121:1095982020. View Article : Google Scholar : PubMed/NCBI | |
|
Hung WY, Lee WJ, Cheng GZ, Tsai CH, Yang YC, Lai TC, Chen JQ, Chung CL, Chang JH and Chien MH: Blocking MMP-12-modulated epithelial-mesenchymal transition by repurposing penfluridol restrains lung adenocarcinoma metastasis via uPA/uPAR/TGF-β/Akt pathway. Cell Oncol (Dordr). 44:1087–1103. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Ranjan A, German N, Mikelis C, Srivenugopal K and Srivastava SK: Penfluridol induces endoplasmic reticulum stress leading to autophagy in pancreatic cancer. Tumour Biol. 39:10104283177055172017. View Article : Google Scholar : PubMed/NCBI | |
|
Ranjan A and Srivastava SK: Penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis. Sci Rep. 6:261652016. View Article : Google Scholar : PubMed/NCBI | |
|
Dandawate P, Kaushik G, Ghosh C, Standing D, Ali Sayed AA, Choudhury S, Subramaniam D, Manzardo A, Banerjee T, Santra S, et al: Diphenylbutylpiperidine Antipsychotic Drugs Inhibit Prolactin Receptor Signaling to Reduce Growth of Pancreatic Ductal Adenocarcinoma in Mice. Gastroenterology. 158:1433–1449.e27. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Chien W, Sun QY, Lee KL, Ding LW, Wuensche P, Torres-Fernandez LA, Tan SZ, Tokatly I, Zaiden N, Poellinger L, et al: Activation of protein phosphatase 2A tumor suppressor as potential treatment of pancreatic cancer. Mol Oncol. 9:889–905. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Ranjan A and Srivastava SK: Penfluridol suppresses glioblastoma tumor growth by Akt-mediated inhibition of GLI1. Oncotarget. 8:32960–32976. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Kim H, Chong K, Ryu BK, Park KJ, Yu MO, Lee J, Chung S, Choi S, Park MJ, Chung YG and Kang SH: Repurposing penfluridol in combination with temozolomide for the treatment of glioblastoma. Cancers (Basel). 11:13102019. View Article : Google Scholar : PubMed/NCBI | |
|
Ranjan A, Wright S and Srivastava SK: Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth. Oncotarget. 8:47632–47641. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Hu J, Cao J, Jin R, Zhang B, Topatana W, Juengpanich S, Li S, Chen T, Lu Z, Cai X and Chen M: Inhibition of AMPK/PFKFB3 mediated glycolysis synergizes with penfluridol to suppress gallbladder cancer growth. Cell Commun Signal. 20:1052022. View Article : Google Scholar : PubMed/NCBI | |
|
van der Horst G, van de Merbel AF, Ruigrok E, van der Mark MH, Ploeg E, Appelman L, Tvingsholm S, Jäätelä M, van Uhm J, Kruithof-de Julio M, et al: Cationic amphiphilic drugs as potential anticancer therapy for bladder cancer. Mol Oncol. 14:3121–3134. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Zheng C, Yu X, Liang Y, Zhu Y, He Y, Liao L, Wang D, Yang Y, Yin X, Li A, et al: Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner. Acta Pharm Sin B. 12:1271–1287. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Wu SY, Wen YC, Ku CC, Yang YC, Chow JM, Yang SF, Lee WJ and Chien MH: Penfluridol triggers cytoprotective autophagy and cellular apoptosis through ROS induction and activation of the PP2A-modulated MAPK pathway in acute myeloid leukemia with different FLT3 statuses. J Biomed Sci. 26:632019. View Article : Google Scholar : PubMed/NCBI | |
|
Tung MC, Lin YW, Lee WJ, Wen YC, Liu YC, Chen JQ, Hsiao M, Yang YC and Chien MH: Targeting DRD2 by the antipsychotic drug, penfluridol, retards growth of renal cell carcinoma via inducing stemness inhibition and autophagy-mediated apoptosis. Cell Death Dis. 13:4002022. View Article : Google Scholar : PubMed/NCBI | |
|
Wu LL, Liu YY, Li ZX, Zhao Q, Wang X, Yu Y, Wang YY, Wang YQ and Luo F: Anti-tumor effects of penfluridol through dysregulation of cholesterol homeostasis. Asian Pac J Cancer Prev. 15:489–494. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Du J, Shang J, Chen F, Zhang Y, Yin N, Xie T, Zhang H, Yu J and Liu F: A CRISPR/Cas9-Based screening for non-homologous end joining inhibitors reveals ouabain and penfluridol as radiosensitizers. Mol Cancer Ther. 17:419–431. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Janssen PA, Niemegeers CJ, Schellekens KH, Lenaerts FM, Verbruggen FJ, Van Nueten JM and Schaper WK: The pharmacology of penfluridol (R 16341) a new potent and orally long-acting neuroleptic drug. Eur J Pharmacol. 11:139–154. 1970. View Article : Google Scholar : PubMed/NCBI | |
|
Airoldi L, Marcucci F, Mussini E and Garattini S: Distribution of penfluridol in rats and mice. Eur J Pharmacol. 25:291–295. 1974. View Article : Google Scholar : PubMed/NCBI | |
|
Andrade C: Psychotropic drugs with long half-lives: Implications for drug discontinuation, occasional missed doses, dosing interval, and pregnancy planning. J Clin Psychiatry. 83:22f145932022. View Article : Google Scholar : PubMed/NCBI | |
|
Bhattacharyya R, Bhadra R, Roy U, Bhattacharyya S, Pal J and Saha SS: Resurgence of penfluridol: Merits and demerits. East J Psychiatry. 18:23–29. 2015. View Article : Google Scholar | |
|
Nikvarz N, Vahedian M and Khalili N: Chlorpromazine versus penfluridol for schizophrenia. Cochrane database Syst Rev. 9:CD0118312017.PubMed/NCBI | |
|
Wang RI, Larson C and Treul SJ: Study of penfluridol and chlorpromazine in the treatment of chronic schizophrenia. J Clin Pharmacol. 22:236–242. 1982. View Article : Google Scholar : PubMed/NCBI | |
|
Andrade C: The practical importance of half-life in psychopharmacology. J Clin Psychiatry. 83:22f145842022. View Article : Google Scholar : PubMed/NCBI | |
|
Clarke Z: Penfluridol. Elsevier; New York, NY: pp. 1–4. 2007 | |
|
Enyeart JJ, Biagi BA, Day RN, Sheu SS and Maurer RA: Blockade of low and high threshold Ca2+ channels by diphenylbutylpiperidine antipsychotics linked to inhibition of prolactin gene expression. J Biol Chem. 265:16373–16379. 1990. View Article : Google Scholar : PubMed/NCBI | |
|
Cabrera M, Gomez N, Remes Lenicov F, Echeverría E, Shayo C, Moglioni A, Fernández N and Davio C: G2/M cell cycle arrest and tumor selective apoptosis of acute leukemia cells by a promising benzophenone thiosemicarbazone compound. PLoS One. 10:e01368782015. View Article : Google Scholar : PubMed/NCBI | |
|
Abbas T and Dutta A: p21 in cancer: Intricate networks and multiple activities. Nat Rev Cancer. 9:400–414. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Boudreau RT, Conrad DM and Hoskin DW: Apoptosis induced by protein phosphatase 2A (PP2A) inhibition in T leukemia cells is negatively regulated by PP2A-associated p38 mitogen-activated protein kinase. Cell Signal. 19:139–151. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Nakamura H and Takada K: Reactive oxygen species in cancer: Current findings and future directions. Cancer Sci. 112:3945–3952. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Yang H, Villani RM, Wang H, Simpson MJ, Roberts MS, Tang M and Liang X: The role of cellular reactive oxygen species in cancer chemotherapy. J Exp Clin Cancer Res. 37:2662018. View Article : Google Scholar : PubMed/NCBI | |
|
Shah MA and Rogoff HA: Implications of reactive oxygen species on cancer formation and its treatment. Semin Oncol. 48:238–245. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Singh R and Manna PP: Reactive oxygen species in cancer progression and its role in therapeutics. Explor Med. 3:43–57. 2022. View Article : Google Scholar | |
|
Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, Castoria G and Migliaccio A: ROS in cancer therapy: The bright side of the moon. Exp Mol Med. 52:192–203. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Kim SJ, Kim HS and Seo YR: Understanding of ROS-Inducing strategy in anticancer therapy. Oxid Med Cell Longev. 2019:53816922019. View Article : Google Scholar : PubMed/NCBI | |
|
Miller DM, Thomas SD, Islam A, Muench D and Sedoris K: c-Myc and cancer metabolism. Clin Cancer Res. 18:5546–5553. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Gao FY, Li XT, Xu K, Wang RT and Guan XX: c-MYC mediates the crosstalk between breast cancer cells and tumor microenvironment. Cell Commun Signal. 21:282023. View Article : Google Scholar : PubMed/NCBI | |
|
Safe S: Specificity Proteins (Sp) and Cancer. Int J Mol Sci. 24:51642023. View Article : Google Scholar : PubMed/NCBI | |
|
Vellingiri B, Iyer M, Devi Subramaniam M, Jayaramayya K, Siama Z, Giridharan B, Narayanasamy A, Abdal Dayem A and Cho SG: Understanding the role of the transcription factor sp1 in ovarian cancer: From theory to practice. Int J Mol Sci. 21:11532020. View Article : Google Scholar : PubMed/NCBI | |
|
Dufour S, Broders-Bondon F and Bondurand N: Chapter 13 - β1-Integrin Function and Interplay during Enteric Nervous System Development. Academic Press; Boston, MA: pp. 153–166. 2015 | |
|
Bergonzini C, Kroese K, Zweemer AJM and Danen EHJ: Targeting integrins for cancer therapy-disappointments and opportunities. Front cell Dev Biol. 10:8638502022. View Article : Google Scholar : PubMed/NCBI | |
|
Valdembri D and Serini G: The roles of integrins in cancer. Fac Rev. 10:452021. View Article : Google Scholar : PubMed/NCBI | |
|
Yousefi H, Vatanmakanian M, Mahdiannasser M, Mashouri L, Alahari NV, Monjezi MR, Ilbeigi S and Alahari SK: Understanding the role of integrins in breast cancer invasion, metastasis, angiogenesis, and drug resistance. Oncogene. 40:1043–1063. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Desgrosellier JS and Cheresh DA: Integrins in cancer: Biological implications and therapeutic opportunities. Nat Rev Cancer. 10:9–22. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Kim SY: Cancer energy metabolism: Shutting power off cancer factory. Biomol Ther (Seoul). 26:39–44. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Chelakkot C, Chelakkot VS, Shin Y and Song K: Modulating glycolysis to improve cancer therapy. Int J Mol Sci. 24:26062023. View Article : Google Scholar : PubMed/NCBI | |
|
Fadaka A, Ajiboye B, Ojo O, Adewale O, Olayide I and Emuowhochere R: Biology of glucose metabolization in cancer cells. J Oncol Sci. 3:45–51. 2017. View Article : Google Scholar | |
|
Lu J, Chen S, Bai X, Liao M, Qiu Y, Zheng LL and Yu H: Targeting cholesterol metabolism in Cancer: From molecular mechanisms to therapeutic implications. Biochem Pharmacol. 218:1159072023. View Article : Google Scholar : PubMed/NCBI | |
|
Fan YJ and Zong WX: The cellular decision between apoptosis and autophagy. Chin J Cancer. 32:121–129. 2013.PubMed/NCBI | |
|
Das S, Shukla N, Singh SS, Kushwaha S and Shrivastava R: Mechanism of interaction between autophagy and apoptosis in cancer. Apoptosis. 26:512–533. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Mulcahy Levy JM and Thorburn A: Autophagy in cancer: Moving from understanding mechanism to improving therapy responses in patients. Cell Death Differ. 27:843–857. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Koukourakis MI, Kalamida D, Giatromanolaki A, Zois CE, Sivridis E, Pouliliou S, Mitrakas A, Gatter KC and Harris AL: Autophagosome Proteins LC3A, LC3B and LC3C have distinct subcellular distribution kinetics and expression in cancer cell lines. PLoS One. 10:e01376752015. View Article : Google Scholar : PubMed/NCBI | |
|
Fares J, Fares MY, Khachfe HH, Salhab HA and Fares Y: Molecular principles of metastasis: A hallmark of cancer revisited. Signal Transduct Target Ther. 5:282020. View Article : Google Scholar : PubMed/NCBI | |
|
Ribatti D, Tamma R and Annese T: Epithelial-Mesenchymal transition in cancer: A historical overview. Transl Oncol. 13:1007732020. View Article : Google Scholar : PubMed/NCBI | |
|
Huang Y, Hong W and Wei X: The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis. J Hematol Oncol. 15:1292022. View Article : Google Scholar : PubMed/NCBI | |
|
Liu ZL, Chen HH, Zheng LL, Sun LP and Shi L: Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduct Target Ther. 8:1982023. View Article : Google Scholar : PubMed/NCBI | |
|
Yang Y and Cao Y: The impact of VEGF on cancer metastasis and systemic disease. Semin Cancer Biol. 86((Pt 3)): 251–261. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang L, Zhang M, Wang L, Li J, Yang T, Shao Q, Liang X, Ma M, Zhang N, Jing M, et al: Identification of CCL4 as an immune-related prognostic biomarker associated with tumor proliferation and the tumor microenvironment in clear cell renal cell carcinoma. Front Oncol. 11:6946642021. View Article : Google Scholar : PubMed/NCBI | |
|
Rezayatmand H, Razmkhah M and Razeghian-Jahromi I: Drug resistance in cancer therapy: The Pandora's Box of cancer stem cells. Stem Cell Res Ther. 13:1812022. View Article : Google Scholar : PubMed/NCBI | |
|
Zheng HC: The molecular mechanisms of chemoresistance in cancers. Oncotarget. 8:59950–59964. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Gong L, Zhang Y, Liu C, Zhang M and Han S: Application of radiosensitizers in cancer radiotherapy. Int J Nanomedicine. 16:1083–1102. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Ashraf-Uz-Zaman M, Shahi S, Akwii R, Sajib MS, Farshbaf MJ, Kallem RR, Putnam W, Wang W, Zhang R, Alvina K, et al: Design, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer. Eur J Med Chem. 209:1128662021. View Article : Google Scholar : PubMed/NCBI | |
|
Ashraf-Uz-Zaman M, Sajib MS, Cucullo L, Mikelis CM and German NA: Analogs of penfluridol as chemotherapeutic agents with reduced central nervous system activity. Bioorg Med Chem Lett. 28:3652–3657. 2018. View Article : Google Scholar : PubMed/NCBI |
