Laetrile and Methotrexate: A Dual-Drug Approach to Inhibiting Cervical Cancer Cell Proliferation

Laetrile and Methotrexate: A Dual-Drug Approach to Inhibiting Cervical Cancer Cell Proliferation

Authors

  • Kawakeb N. Abdulla Iraqi National Cancer Research Center/University of Baghdad, Baghdad, Iraq
  • Rasha Kareem Khudhur Pharmacology Department, College of Medicine, University of Misan, Iraq https://orcid.org/0000-0002-4508-109X
  • Ali Muafaq Said Al-Amarah University College, Iraq
  • Azal Hamoody Jumaa Iraqi National Cancer Research Center/University of Baghdad, Baghdad, Iraq https://orcid.org/0009-0003-4412-1357
  • Youssef Shakuri Yasin Bilad Alrafidain University, Iraq https://orcid.org/0000-0003-1433-1858

DOI:

https://doi.org/10.30683/1929-2279.2025.14.06

Keywords:

Cervical cancer, Hela cancer cell line, combination index, dose reduction index, cytotoxicity, laetrile, methotrexate

Abstract

Objective: This study was done to evaluate the efficacy of laetrile methotrexate combination in inhibiting cervical cancer proliferation and identify the synergistic effects between them

Method: During three incubation periods, 24, 48, and 72 hours, the antiproliferative impact of the laetrile and methotrexate combination was assessed by employing the Hela cell line, a human cervical cancer cell line. The concentration range of the tested reagent varied from 0.1 to 1000 µg/ml for each laetrile and methotrexate. At the same time, the concentration of the mixture varied from 0.05 to 500 µg/ml for both laetrile and methotrexate. The combination index value was used to identify whether there was a synergistic impact between laetrile and methotrexate in the combination. The dose reduction index was employed to ascertain the extent of the reduction in the concentration of the constituent mix, which resulted in a notable cytotoxic impact.

Result: The study results revealed that the combination of laetrile and methotrexate successfully inhibited the proliferation of cervical cancer cells in a manner that depended on the concentration and duration of treatment. The combination index value exhibited a significant synergistic impact between laetrile and methotrexate in all concentrations except 1000 µg/ml. Furthermore, the dose reduction index outcomes showed that the combination minimized the required concentration of laetrile and methotrexate.

Conclusion: Concerning the study findings and their defined pharmacokinetic and safety characteristics of mixture drugs. The laetrile-methotrexate mixture offers an attractive and safer option for the treatment of cervical cancer.

References

Rana RM, Rampogu S, Abid NB, Zeb A, Parate S, Lee G, et al. In silico study identified methotrexate analog as potential inhibitor of drug resistant human dihydrofolate reductase for cancer therapeutics 2020; 25(15): 3510. DOI: https://doi.org/10.3390/molecules25153510

Lee HM, Moon AJB, therapeutics. Amygdalin regulates apoptosis and adhesion in Hs578T triple-negative breast cancer cells 2016; 24(1): 62. DOI: https://doi.org/10.4062/biomolther.2015.172

Khashman BM, Abdulla KN, Karim S, Alhashimi S, Mohammed ML, Sarah NA. The Effect of Twist Expression On The Development Ofcervical Carcinoma in A Group Of Iraqi Women Infected with Hpv. Biochem Cell Arch 2019; 19(2): 3913-6.

Abdulla KN, Khashman BM, Alheshimi SJ. The Immunohistochemical Evaluation of BRCA2 Expression with HPV Infection in a Group of Iraqi Women with Cervical Carcinoma. Indian Journal of Public Health Research & Development 2019; 10(9). DOI: https://doi.org/10.5958/0976-5506.2019.02590.7

Guo M, Kong Q, Wang W, Yu HJPB. Biotransformation of amygdalin by lactic acid bacteria fermentation 2023; 132: 221-7. DOI: https://doi.org/10.1016/j.procbio.2023.07.022

Ali B, Rawal YK, Thayes CJAJoM, Plants A. Nutritional composition, phytochemical screening, antioxidant, GC-MS, and FTIR analysis of methanolic extract of apricot, Prunus armeniaca kernel from Ladakh, India 2022; 8(3): 149-69.

Qi X, Wong BL, Lau SH, Ng KT-P, Kwok SY, Sun CK-W, et al. A hemoglobin-based oxygen carrier sensitized Cisplatin based chemotherapy in hepatocellular carcinoma 2017; 8(49): 85311. DOI: https://doi.org/10.18632/oncotarget.19672

Popa V-M, Raba D-N, Moldovan C, Poiana M-A, Misca C-D, Dumbrava D-G, et al. A review of amygdalin characteristics 2021; 27(4): 409-15.

Jumaa AH, Hussein SMJIJoC, Genetics M. Study the in vitro effect of alcoholic extract of Prunus aremasia kernels, Methotreaxte, amygdalin and the combination between them on Hela cancer cell line 2015; 8(2). DOI: https://doi.org/10.29409/ijcmg.v8i2.152

Jarad A. Diabetic wound healing enhancement by tadalafil 2020.

Mohammad NSK, Ali AH, Salah LDFSJJoSiFS. Prunus armeniaca Seeds Extract Inhibits Cell Proliferation and Enhances Cell Death in Cancer Cells 2023; 10(1S): 4178-95.

Elad S, Ranna V, Ariyawardana A, Correa MEP, Tilly V, Nair RG, et al. A systematic review of oral herpetic viral infections in cancer patients: commonly used outcome measures and interventions 2017; 25: 687-700. DOI: https://doi.org/10.1007/s00520-016-3477-7

Said AM, Abdulla KN, Ahmed NH, Yasin YS. Antiproliferative Impact of Linagliptin on the Cervical Cancer Cell Line. Asian Pacific Journal of Cancer Prevention: APJCP 2024; 25(9): 3293. DOI: https://doi.org/10.31557/APJCP.2024.25.9.3293

Jumaa AH, Al Uboody WSH, Hady AMJJoPS, Research. Esomeprazole and Amygdalin combination cytotoxic effect on human cervical cancer cell line (Hela cancer cell line) 2018; 10(9): 2236-41.

Jumaa AH, Jarad AS, Al Uboody WSHJM-lU. The effect of esomeprazole on cell line human cervical cancer 2020; 20(1).

Jumaa AHJIJoC, Genetics M. The cytotoxic effect of Vincristine-Amygdalin combination on human cervical cancer cell line (Hela cancer cell line) 2016; 9(2). DOI: https://doi.org/10.29409/ijcmg.v9i2.187

Yasin YS, Jumaa AH, Jabbar S, Abdulkareem AHJAPJoCPA. Effect of Laetrile Vinblastine Combination on the Proliferation of the Hela Cancer Cell Line 2023; 24(12): 4329. DOI: https://doi.org/10.31557/APJCP.2023.24.12.4329

Wang L, Huang X, Chai Y, Zou L, Chedrawe M, Ding YJOR. Octreotide inhibits the proliferation of gastric cancer cells through P300-HAT activity and the interaction of ZAC and P300 2017; 37(4): 2041-8. DOI: https://doi.org/10.3892/or.2017.5451

Almahdawy S, Said AM, Abbas IS, Dawood AH. The evaluation of antimicrobial and cytotoxic activity of the essential oil extracted from the aerial parts of southernwood herb (Artemisia abrotanum L.) that recently grown in Iraq. Asian Journal of Pharmaceutical and Clinical Research 2017; 10(10). DOI: https://doi.org/10.22159/ajpcr.2017.v10i10.21725

Mensoor M, Said A. Determination of heavy metals in freshwater fishes of the Tigris River in Baghdad. Fishes 2018; 3(2): 23. DOI: https://doi.org/10.3390/fishes3020023

Said AM, Numan IT, HAMAD MN. Study of the cytotoxic and genotoxic effects for fractioniated extracts of convolulus arvensis on bone marrow in mice. International Journal of Pharmacy and Pharmaceutical Sciences Received 2013; 18: 303-5.

Milazzo S, Ernst E, Lejeune S, Boehm K. Laetrile treatment for cancer. Cochrane Database of Systematic Reviews 2006(2). DOI: https://doi.org/10.1002/14651858.CD005476.pub2

Dolgin JL. Challenging Medicine: Ivermectin Cases, Medical Futility Cases and the Patient-Physician Relationship. Quinnipiac L Rev 2023; 42: 363.

Rahman AJMAPP. A review on medicinal plants with anticancer activity available in Bangladesh 2018; 1(4). DOI: https://doi.org/10.31031/MAPP.2018.01.000516

Al-Hraishawi H, Al-Saadi N, Jabbar S. In vitro analysis: the anticancer activity of zinc oxide nanoparticles from Cinnamomum verum. Journal of Nanostructures 2023; 13(1): 146-50.

Akbari B, Baghaei‐Yazdi N, Bahmaie M, Mahdavi Abhari FJB. The role of plant‐derived natural antioxidants in reduction of oxidative stress 2022; 48(3): 611-33. DOI: https://doi.org/10.1002/biof.1831

Rahbari R, Sheahan T, Modes V, Collier P, Macfarlane C, Badge RMJB. A novel L1 retrotransposon marker for HeLa cell line identification 2009; 46(4): 277-84. DOI: https://doi.org/10.2144/000113089

Bor T, Aljaloud SO, Gyawali R, Ibrahim SA. Antimicrobials from herbs, spices, and plants. Fruits, vegetables, and herbs: Elsevier; 2016. p. 551-78. DOI: https://doi.org/10.1016/B978-0-12-802972-5.00026-3

Zhang Y, Qi D, Gao Y, Liang C, Zhang Y, Ma Z, et al. History of uses, phytochemistry, pharmacological activities, quality control and toxicity of the root of Stephania tetrandra S. Moore: A review. Journal of ethnopharmacology 2020; 260: 112995. DOI: https://doi.org/10.1016/j.jep.2020.112995

Meyer CT, Wooten DJ, Lopez CF, Quaranta V. Charting the Fragmented Landscape of Drug Synergy. Trends Pharmacol Sci 2020; 41(4): 266-80. DOI: https://doi.org/10.1016/j.tips.2020.01.011

Mohammed BJ, AL-Thwani AN, Kadhim AAAJIJE. Effect of Nicotine Injection on Tumor Suppressor Gene P53 Expression in Lung of Mice 2020; 47(12): 41-4.

Ma M, Liang J, Zhang D, Xu X, Cheng Q, Xiao Z, et al. Monitoring treatment efficacy of antiangiogenic therapy combined with hypoxia-activated prodrugs online using functional MRI 2021; 11: 672047. DOI: https://doi.org/10.3389/fonc.2021.672047

Giannenas I, Sidiropoulou E, Bonos E, Christaki E, Florou-Paneri P. The history of herbs, medicinal and aromatic plants, and their extracts: Past, current situation and future perspectives. Feed additives: Elsevier; 2020. p. 1-18. DOI: https://doi.org/10.1016/B978-0-12-814700-9.00001-7

Sekino Y, Teishima JJCDR. Molecular mechanisms of docetaxel resistance in prostate cancer 2020; 3(4): 676. DOI: https://doi.org/10.20517/cdr.2020.37

Makarević J, Tsaur I, Juengel E, Borgmann H, Nelson K, Thomas C, et al. Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro 2016; 147: 137-42. DOI: https://doi.org/10.1016/j.lfs.2016.01.039

Lorestani F, Movahedian A, Mohammadalipour A, Hashemnia M, Aarabi MHJCJoP, Pharmacology. Astaxanthin prevents nephrotoxicity through Nrf2/HO-1 pathway 2023; 102(2): 128-36. DOI: https://doi.org/10.1139/cjpp-2023-0015

Alonzo JR, Venkataraman C, Field MS, Stover PJJJoBC. The mitochondrial inner membrane protein MPV17 prevents uracil accumulation in mitochondrial DNA 2018; 293(52): 20285-94. DOI: https://doi.org/10.1074/jbc.RA118.004788

Khalifa MF, Ghadhban AGZA, Hade IM, Ali MM. Evaluation of quality of life for women with breast cancer. Scripta Medica 2024; 55(1): 115-8. DOI: https://doi.org/10.5937/scriptamed55-47068

Joo W-S, Jeong J-S, Kim H, Lee Y-M, Lee J-H, Hong S-PJAopr. Prevention of epimerization and quantitative determination of amygdalin in Armeniacae Semen with Schizandrae Fructus solution 2006; 29: 1096-101. DOI: https://doi.org/10.1007/BF02969298

Barakat H, Aljutaily T, Almujaydil MS, Algheshairy RM, Alhomaid RM, Almutairi AS, et al. Amygdalin: a review on its characteristics, antioxidant potential, gastrointestinal microbiota intervention, anticancer therapeutic and mechanisms, toxicity, and encapsulation 2022; 12(10): 1514. DOI: https://doi.org/10.3390/biom12101514

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Published

2025-05-02

How to Cite

Abdulla, K. N. ., Khudhur, R. K. ., Said, A. M. ., Jumaa, A. H. ., & Yasin, Y. S. . (2025). Laetrile and Methotrexate: A Dual-Drug Approach to Inhibiting Cervical Cancer Cell Proliferation. Journal of Cancer Research Updates, 14, 52–62. https://doi.org/10.30683/1929-2279.2025.14.06

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