Interlinking Human-Derived Leukemia Cells with Clinicopathological Therapeutics: Exploring Capsaicin's Anti-Cancer Mechanisms/potential for Leukemia Patients: Interlinking Human-Derived Leukemia Cells with Clinicopathological Therapeutics

Maryam Mastoor; Faiza  Choudhry; Aina Khurshid; Ama tul Naval; Jamal Asad; Shagufta Khaliq; Durga Devi

doi:10.54393/pjhs.v5i09.2266

Authors

Maryam Mastoor Department of Biochemistry, Amna Inayat Medical College, Lahore, Pakistan
Faiza Choudhry Department of Medicine, People University of Medical and Health Sciences, Nawabshah, Pakistan
Aina Khurshid Department of Biochemistry, Multan Medical and Dental College, Multan, Pakistan
Ama tul Naval Department of Pathology, Watim Medical College, Rawalpindi, Pakistan
Jamal Asad Department of Biochemistry, Multan Medical and Dental College, Multan, Pakistan
Shagufta Khaliq Department of Physiology, Amna Inayat Medical College, Lahore, Pakistan
Durga Devi Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v5i09.2266

Keywords:

Capsaicin, Anti-Proliferative, Human-Derived Leukemia Cells, Apoptosis

Abstract

Capsaicin, a bioactive compound isolated from chilli peppers, comes out as a potential agent for its anti-proliferation role in leukemia patients’ therapy. Objectives: This systematic review describes the Clinicopathological therapeutic potential of capsaicin against leukemia emphasizing the mechanism by which it inhibits growth through apoptosis, the cell cycle, and regulation of oncogenic signalling pathways in human-derived leukemia cell lines. Methods: According to PRISMA guidelines, the 75 studies were obtained from the various databases January 2013 and April 2024; Semantic Scholar, Google Scholar, PubMed as well as Frontiers and Link Springer. 50% (38) of the articles were taken from Semantic Scholar, 30% (22) from Google Scholar and 20% (15) from other search engines including PubMed and Link Springer. The papers included the inclusion criteria of PRISMA based on demographics, key outcomes and Anti-Cancer mechanisms majorly. Results: Capsaicin research published in America, Europe, Asia and Africa proves that it regulates vital processes at the cellular level including production of ROS, inhibition of NF-κB, STAT3, MAPK and cellular apoptosis. As human-derived cell lines are playing a pivotal role in cancer therapy, silicon methodologies along with in-vitro and in-vivo verification also shed more light on the improvement by capsaicin of the effectiveness of standard chemotherapeutic agents in combination with preferential killing of leukemic cells. Conclusions: Significantly, there were low levels of cytotoxicity of capsaicin to normal peripheral blood hematopoietic cells indicating that the compound is safe to use inhibiting the key oncogenic pathways and enhancing the efficacy of existing chemotherapeutic agents makes it a promising candidate for future therapeutic development.

References

Davis AS, Viera AJ, Mead MD. Leukemia: An Overview for Primary Care. American Family Physician. 2014 May; 89(9): 731-8.

Garcia-Manero G, Faderl S, O'Brien S, Cortes J, Talpaz M, Kantarjian HM. Chronic Myelogenous Leukemia: A Review and Update of Therapeutic Strategies. Cancer. 2003 Aug; 98(3): 437-57. doi: 10.1002/cncr.11520. DOI: https://doi.org/10.1002/cncr.11520

Huang J, Chan SC, Ngai CH, Lok V, Zhang L, Lucero-Prisno III DE et al. Disease Burden, Risk Factors, And Trends of Leukaemia: A Global Analysis. Frontiers in Oncology. 2022 Jul; 12: 904292. doi: 10.3389/fonc.2022.904292. DOI: https://doi.org/10.3389/fonc.2022.904292

Zhu H, Dong B, Zhang Y, Wang M, Rao J, Cui B et al. Integrated Genomic Analyses Identify High-Risk Factors and Actionable Targets in T-Cell Acute Lymphoblastic Leukemia. Blood Science. 2022 Jan; 4(01): 16-28. doi: 10.1097/BS9.0000000000000102. DOI: https://doi.org/10.1097/BS9.0000000000000102

Bao Z, Dai X, Wang P, Tao Y, Chai D. Capsaicin Induces Cytotoxicity in Human Osteosarcoma MG63 Cells Through TRPV1-Dependent and-Independent Pathways. Cell Cycle. 2019 Jun; 18(12): 1379-92. doi: 10.1080/15384101.2019.1618119. DOI: https://doi.org/10.1080/15384101.2019.1618119

Radhakrishna GK, Ammunje DN, Kunjiappan S, Ravi K, Vellingiri S, Ramesh SH et al. A Comprehensive Review of Capsaicin and Its Role in Cancer Prevention and Treatment. Drug Research. 2024 May; 74(05): 195-207. doi: 10.1055/a-2309-5581. DOI: https://doi.org/10.1055/a-2309-5581

Singh SA, Uddin MO, Khan MM, Singh SA, Chishti AS, Bhat UH. Therapeutic Properties of Capsaicin: A Medicinally Important Bio-Active Constituent of Chilli Pepper. Asian Journal of Pharmaceutical and Clinical Research. 2022 Jul; 15(7): 47-58. doi: 10.22159/ajpcr.2022.v15i7.44405. DOI: https://doi.org/10.22159/ajpcr.2022.v15i7.44405

Zhai K, Liskova A, Kubatka P, Büsselberg D. Calcium Entry Through TRPV1: A Potential Target for the Regulation of Proliferation and Apoptosis in Cancerous and Healthy Cells. International Journal of Molecular Sciences. 2020 Jun; 21(11): 4177. doi: 10.3390/ijms21114177. DOI: https://doi.org/10.3390/ijms21114177

Shi Y, Chen C, Huang Y, Xu Y, Xu D, Shen H, Ye X, Jin J, Tong H, Yu Y, Tang X. Global Disease Burden and Trends of Leukemia Attributable to Occupational Risk from an Observational Trend Study. Insights in Occupational Health and Safety: 2022. 2023 Oct: 51. doi: 10.3389/fpubh.2022.1015861. DOI: https://doi.org/10.3389/fpubh.2022.1015861

Martelli A, Omrani M, Zarghooni M, Citi V, Brogi S, Calderone V et al. New Visions on Natural Products and Cancer Therapy: Autophagy and Related Regulatory Pathways. Cancers. 2022 Nov; 14(23): 5839. doi: 10.3390/cancers14235839. DOI: https://doi.org/10.3390/cancers14235839

Luján-Méndez F, Roldán-Padrón O, Castro-Ruíz JE, López-Martínez J, García-Gasca T. Capsaicinoids and Their Effects on Cancer: The “Double-Edged Sword” Postulate from the Molecular Scale. Cells. 2023 Nov; 12(21): 2573. doi: 10.3390/cells12212573. DOI: https://doi.org/10.3390/cells12212573

Lajevardian SA, Alibakhshi A, Hosseinzadeh S, Mobaraki F, Movahedi M, Hatamie S et al. Synergistic Effect of Cobalt Ferrite-Graphene Oxide Based Hyperthermia and Capsaicin to Induce Apoptosis and Inhibit Telomerase Activity in Breast Cancer Cells. Advances in Natural Sciences: Nanoscience and Nanotechnology. 2024 Aug; 15(3): 035017. doi: 10.1088/2043-6262/ad71a5. DOI: https://doi.org/10.1088/2043-6262/ad71a5

Patwardhan CA, Kommalapati VK, Llbiyi T, Singh D, Alfa E, Horuzsko A et al. Capsaicin Binds the N-Terminus of Hsp90, Induces Lysosomal Degradation of Hsp70, and Enhances the Anti-Tumor Effects of 17-AAG (Tanespimycin). Scientific Reports. 2023 Aug; 13(1): 13790. doi: 10.1038/s41598-023-40933-9. DOI: https://doi.org/10.1038/s41598-023-40933-9

Nibret E, Krstin S, Wink M. In Vitro Anti-Proliferative Activity of Selected Nutraceutical Compounds in Human Cancer Cell Lines. BioMed Central Research Notes. 2021 Dec; 14: 1-6. doi: 10.1186/s13104-020-05435-1. DOI: https://doi.org/10.1186/s13104-020-05435-1

Richbart SD, Friedman JR, Brown KC, Gadepalli RS, Miles SL, Rimoldi JM et al. Nonpungent N-AVAM Capsaicin Analogues and Cancer Therapy. Journal of Medicinal Chemistry. 2021 Jan; 64(3): 1346-61. doi: 10.1021/acs.jmedchem.0c01679. DOI: https://doi.org/10.1021/acs.jmedchem.0c01679

Al-Samydai A, Alshaer W, Al-Dujaili EA, Azzam H, Aburjai T. Preparation, Characterization, and Anticancer Effects of Capsaicin-Loaded Nanoliposomes. Nutrients. 2021 Nov; 13(11): 3995. doi: 10.3390/nu13113995. DOI: https://doi.org/10.3390/nu13113995

Naaz F, Ahmad F, Lone BA, Khan A, Sharma K, IntzarAli et al. Apoptosis-inducing 1, 3, 4-oxadiazole Conjugates of Capsaicin: There in Vitro Antiproliferative and in Silico Studies. American Chemical Society Medicinal Chemistry Letters. 2021 Oct; 12(11): 1694-702. doi: 10.1021/acsmedchemlett.1c00304. DOI: https://doi.org/10.1021/acsmedchemlett.1c00304

Kaymaz BT, Çetintaş VB, Aktan Ç, Kosova B. MicroRNA-520a-5p Displays a Therapeutic Effect Upon Chronic Myelogenous Leukemia Cells by Targeting STAT3 and Enhances the Anti Carcinogenic Role of Capsaicin. Tumor Biology. 2014 Sep; 35: 8733-42. doi: 10.1007/s13277-014-2138-z. DOI: https://doi.org/10.1007/s13277-014-2138-z

Yin Q, Wang L, Yu H, Chen D, Zhu W, Sun C. Pharmacological Effects of Polyphenol Phytochemicals on The JAK-STAT Signaling Pathway. Frontiers in Pharmacology. 2021 Sep; 12: 716672. doi: 10.3389/fphar.2021.716672. DOI: https://doi.org/10.3389/fphar.2021.716672

Moriguchi M, Watanabe T, Kadota A, Fujimuro M. Capsaicin Induces Apoptosis in KSHV-Positive Primary Effusion Lymphoma by Suppressing ERK and P38 MAPK Signaling and IL-6 Expression. Frontiers in Oncology. 2019 Feb; 9: 83. doi: 10.3389/fonc.2019.00083. DOI: https://doi.org/10.3389/fonc.2019.00083

Maggi F, Morelli MB, Aguzzi C, Zeppa L, Nabissi M, Polidori C et al. Calcium Influx, Oxidative Stress, And Apoptosis Induced by TRPV1 in Chronic Myeloid Leukemia Cells: Synergistic Effects with Imatinib. Frontiers in Molecular Biosciences. 2023 Feb; 10: 1129202. doi: 10.3389/fmolb.2023.1129202. DOI: https://doi.org/10.3389/fmolb.2023.1129202

Lin CH, Lu WC, Wang CW, Chan YC, Chen MK. Capsaicin Induces Cell Cycle Arrest and Apoptosis in Human KB Cancer Cells. BioMed Central Complementary and Alternative Medicine. 2013 Dec; 13: 1-9. doi: 10.1186/1472-6882-13-46. DOI: https://doi.org/10.1186/1472-6882-13-46

Clark R and Lee SH. Anticancer Properties of Capsaicin Against Human Cancer. Anticancer research. 2016 Mar; 36(3): 837-43.

Moriguchi M, Watanabe T, Fujimuro M. Capsaicin Induces ATF4 Translation with Upregulation of CHOP, GADD34 and PUMA. Biological and Pharmaceutical Bulletin. 2019 Aug; 42(8): 1428-32. doi: 10.1248/bpb.b19-00303. DOI: https://doi.org/10.1248/bpb.b19-00303

Adetunji TL, Olawale F, Olisah C, Adetunji AE, Aremu AO. Capsaicin: A Two-Decade Systematic Review of Global Research Output and Recent Advances Against Human Cancer. Frontiers in Oncology. 2022 Jul; 12: 908487. doi: 10.3389/fonc.2022.908487. DOI: https://doi.org/10.3389/fonc.2022.908487

Khaliq HM, Aziz O, Wadhwa M, Imran S. In Vitro Insights: Investigating Pro-Apoptotic Potential of Capsaicin Against HL-60, Human Leukemia Cell Line. Rawal Medical Journal. 2024 Aug; 49(3): 661-.

Allison M, Mathews J, Gilliland T, Mathew SO. Natural Killer Cell-Mediated Immunotherapy for Leukemia. Cancers. 2022 Feb; 14(3): 843. doi: 10.3390/cancers14030843. DOI: https://doi.org/10.3390/cancers14030843

Bhagwat DA, Swami PA, Nadaf SJ, Choudhari PB, Kumbar VM, More HN et al. Capsaicin Loaded Solid SNEDDS for Enhanced Bioavailability and Anticancer Activity: In-Vitro, In-Silico, and In-Vivo Characterization. Journal of Pharmaceutical Sciences. 2021 Jan; 110(1): 280-91. doi: 10.1016/j.xphs.2020.10.020. DOI: https://doi.org/10.1016/j.xphs.2020.10.020

Kocak M, Ezazi Erdi S, Jorba G, Maestro I, Farrés J, Kirkin V et al. Targeting Autophagy in Disease: Established and New Strategies. Autophagy. 2022 Mar; 18(3): 473-95. doi: 10.1080/15548627.2021.1936359. DOI: https://doi.org/10.1080/15548627.2021.1936359

Luo Y, Wang X, Shen J, Yao J. Macrophage Migration Inhibitory Factor in the Pathogenesis of Leukemia. International Journal of Oncology. 2021 Aug; 59(2): 1-0. doi: 10.3892/ijo.2021.5242. DOI: https://doi.org/10.3892/ijo.2021.5242

Bhat AA, Younes SN, Raza SS, Zarif L, Nisar S, Ahmed I et al. Role of Non-Coding RNA Networks in Leukemia Progression, Metastasis and Drug Resistance. Molecular Cancer. 2020 Dec; 19: 1-21. doi: 10.1186/s12943-020-01175-9. DOI: https://doi.org/10.1186/s12943-020-01175-9

Egan G, Khan DH, Lee JB, Mirali S, Zhang L, Schimmer AD. Mitochondrial and Metabolic Pathways Regulate Nuclear Gene Expression to Control Differentiation, Stem Cell Function, and Immune Response in Leukemia. Cancer Discovery. 2021 May; 11(5): 1052-66. doi: 10.1158/2159-8290.CD-20-1227. DOI: https://doi.org/10.1158/2159-8290.CD-20-1227

Guo Y, Wang W, Sun H. A Systematic Review and Meta-Analysis on the Risk Factors of Acute Myeloid Leukemia. Translational Cancer Research. 2022 Apr; 11(4): 796. doi: 10.21037/tcr-22-27. DOI: https://doi.org/10.21037/tcr-22-27

Min JK, Han KY, Kim EC, Kim YM, Lee SW, Kim OH et al. Capsaicin Inhibits in Vitro and in Vivo Angiogenesis. Cancer Research. 2004 Jan; 64(2): 644-51. doi: 10.1158/0008-5472.CAN-03-3250. DOI: https://doi.org/10.1158/0008-5472.CAN-03-3250

Khan A, Singh VK, Thakral D, Gupta R. Autophagy in Acute Myeloid Leukemia: A Paradoxical Role in Chemoresistance. Clinical and Translational Oncology. 2022 Aug; 24(8): 1459-69. doi: 10.1007/s12094-022-02804-z. DOI: https://doi.org/10.1007/s12094-022-02804-z

Werner J. Capsaicinoids–Properties and Mechanisms of Pro-Health Action. Analytical Methods in the Determination of Bioactive Compounds and Elements in Food. 2021 Feb: 193-225. doi: 10.1007/978-3-030-61879-7_8. DOI: https://doi.org/10.1007/978-3-030-61879-7_8

Bayraktar A, Li X, Kim W, Zhang C, Turkez H, Shoaie S et al. Drug Repositioning Targeting Glutaminase Reveals Drug Candidates for the Treatment of Alzheimer’s Disease Patients. Journal of Translational Medicine. 2023 May; 21(1): 332. doi: 10.1186/s12967-023-04192-6. DOI: https://doi.org/10.1186/s12967-023-04192-6

Hail N. Mechanisms of Vanilloid-Induced Apoptosis. Apoptosis. 2003 Jun; 8: 251-62. doi: 10.1023/A:1023620821878. DOI: https://doi.org/10.1023/A:1023620821878

Soltani A, Shams Abadi MS, Raeisi M, Kouhihabibidehkordi G, Eshaghi F, Mohreh O et al. Apoptosis-Inducing Plant-Based Phenolic Compounds Are Effective on Leukemia Cell Lines. Current Pharmaceutical Design. 2023 Apr; 29(14): 1092-104. doi: 10.2174/1381612829666230417110032. DOI: https://doi.org/10.2174/1381612829666230417110032

de-Sá-Júnior PL, Pasqualoto KF, Ferreira AK, Tavares MT, Damião MC, de Azevedo RA et al. RPF101, A New Capsaicin-Like Analogue, Disrupts the Microtubule Network Accompanied by Arrest in the G2/M Phase, Inducing Apoptosis and Mitotic Catastrophe in the MCF-7 Breast Cancer Cells. Toxicology and Applied Pharmacology. 2013 Feb; 266(3): 385-98. doi: 10.1016/j.taap.2012.11.029. DOI: https://doi.org/10.1016/j.taap.2012.11.029

Dwivedi SD, Singh MR, Singh D, Dubey S, Dixit AK, Gadkari P et al. Capsaicinoids: Nanoformulations for Improved Therapeutic Applications. In Capsaicinoids: From Natural Sources to Biosynthesis and their Clinical Applications. Singapore: Springer Nature Singapore. 2024 Apr: 529-548. doi: 10.1007/978-981-99-7779-6_25. DOI: https://doi.org/10.1007/978-981-99-7779-6_25

Omari SA, Adams MJ, Kunde DA, Geraghty DP. Capsaicin-Induced Death of Human Haematological Malignant Cell Lines is Independent of TRPV1 Activation. Pharmacology. 2016 Jun; 98(1-2): 79-86. doi: 10.1159/000445437. DOI: https://doi.org/10.1159/000445437

Basumatary M and Talukdar A. Exploring the Potential of Capsaicin in Cancer Therapy: In Vitro and in Vivo Effects and Their Mechanism of Action. In Capsaicinoids: From Natural Sources to Biosynthesis and their Clinical Applications. Singapore: Springer Nature Singapore. 2024 Apr: 427-461. doi: 10.1007/978-981-99-7779-6_20. DOI: https://doi.org/10.1007/978-981-99-7779-6_20

Szoka L and Palka J. Capsaicin Up-Regulates Pro-Apoptotic Activity of Thiazolidinediones in Glioblastoma Cell Line. Biomedicine and Pharmacotherapy. 2020 Dec; 132: 110741. doi: 10.1016/j.biopha.2020.110741. DOI: https://doi.org/10.1016/j.biopha.2020.110741