The Herbal Supplement Induces G2 Arrest and Apoptosis in A549 Cells In Vitro
Year 2023,
Volume: 40 Issue: 3, 627 - 632, 30.09.2023
Melek Yüce
,
Cagri Gumuskaptan
Abstract
In treating cancer, an important health problem, alternative treatment approaches with herbal content continue to be investigated. The study was carried out to determine an herbal supplement's cytotoxic effect and anticancer potential on lung cancer cells. Human lung adenocarcinoma A549 cells were treated with the herbal supplement and cisplatin. The supplement's growth inhibitory and anticancer potential were determined by MTT assay, Annexin V–PI apoptosis assay, cell cycle analysis, and real-time PCR analysis of the apoptosis and cell cycle-related genes. The herbal supplement was determined to have significant growth inhibitory effects on A549 cells. Results of the apoptosis and cell cycle analysis showed that the supplement caused a significant increase in the rate of late apoptotic cells and induced G2 arrest. Gene expression analysis results showed that pro-apoptotic BAK1, BAX, APAF1, and cell cycle inhibitor CDKN1A significantly increased mRNA levels without altering BCL2 and TP53 expressions in A549 cells. Our experiments have shown that the herbal supplement has a potential anticancer effect on the lung cancer A549 cell line through growth inhibition and apoptosis. However, more in vitro studies and in vivo experiments are needed.
Supporting Institution
Ondokuz Mayıs University
Project Number
PYO.KÖK.1901.20.001
Thanks
The authors wish to Yeditepe University Regenerative Biology Research Group Head Assoc. Dr. Fatih Kocabaş
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Year 2023,
Volume: 40 Issue: 3, 627 - 632, 30.09.2023
Melek Yüce
,
Cagri Gumuskaptan
Project Number
PYO.KÖK.1901.20.001
References
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- 2. Baharuddin P, Satar N, Fakiruddin KS, Zakaria N, Lim MN, Yusoff NM, et al. Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines. Oncology reports. 2016;35(1):13-25.
- 3. Cooper S, Spiro SG. Small cell lung cancer: treatment review. Respirology. 2006;11(3):241-8.
- 4. Yang S, Zhang Z, Wang Q. Emerging therapies for small cell lung cancer. Journal of hematology & oncology. 2019;12:1-11.
- 5. Smagurauskaite G, Mahale J, Brown K, Thomas AL, Howells LM. New paradigms to assess consequences of long-term, low-dose curcumin exposure in lung cancer cells. Molecules. 2020;25(2):366.
- 6. Cao X, Ganti AK, Stinchcombe T, Wong ML, Ho JC, Shen C, et al. Predicting risk of chemotherapy-induced severe neutropenia: a pooled analysis in individual patients data with advanced lung cancer. Lung Cancer. 2020;141:14-20.
- 7. Zulkapli R, Abdul Razak F, Zain RB. Vitamin E (α-Tocopherol) exhibits antitumour activity on Oral squamous carcinoma cells ORL-48. Integrative Cancer Therapies. 2017;16(3):414-25.
- 8. Buhrmann C, Yazdi M, Dezfouli AB, Sahraneshin FS, Ebrahimi SM, Ghaffari SH, et al. Significant decrease in the viability and tumor stem cell marker expression in tumor cell lines treated with curcumin. Journal of Herbal
Medicine. 2020;22:100339.
- 9. Waheed Roomi M, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. In vivo and in vitro antitumor effect of a unique nutrient mixture on lung cancer cell line A-549. Experimental lung research. 2006;32(9):441-53.
- 10. Roomi MW, Kalinovsky T, Niedzwiecki A, Rath M. Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human lung cancer and mesothelioma cell lines. International Journal of Oncology. 2013;42(6):1883-9.
- 11. Olaku O, White JD. Herbal therapy use by cancer patients: a literature review on case reports. European journal of cancer. 2011;47(4):508-14.
- 12. Roomi MW, Roomi NW, Kalinovsky T, Rath M, Niedzwiecki A. Chemopreventive effect of a novel nutrient mixture on lung tumorigenesis induced by urethane in male A/J mice. Tumori Journal. 2009;95(4):508-13.
- 13. Saydam F, Nalkiran H, Ozkaya S, Dirican A. Analysis of Bioactive Components of Dr. M. Healing® As a Mixed Herbal Product J Alt Med Res. 2018;3(1):102.
- 14. Ugawa T, Kakuta H, Moritani H, Matsuda K, Ishihara T, Yamaguchi M, et al. YM‐53601, a novel squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in several animal species. British journal of pharmacology. 2000;131(1):63-70.
- 15. Shokoohinia Y, Jafari F, Mohammadi Z, Bazvandi L, Hosseinzadeh L, Chow N, et al. Potential anticancer properties of osthol: A comprehensive mechanistic review. Nutrients. 2018;10(1):36.
- 16. Chen Y, Ma J, Wang F, Hu J, Cui A, Wei C, et al. Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells. Immunopharmacology and immunotoxicology. 2013;35(1):43-51.
- 17. Makarević J, Rutz J, Juengel E, Kaulfuss S, Reiter M, Tsaur I, et al. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2. PloS one. 2014;9(8):e105590.
- 18. Park H-J, Yoon S-H, Han L-S, Zheng L-T, Jung K-H, Uhm Y-K, et al. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells. World journal of gastroenterology: WJG. 2005;11(33):5156.
- 19. Qian L, Xie B, Wang Y, Qian J. Amygdalin-mediated inhibition of non-small cell lung cancer cell invasion in vitro. International journal of clinical and experimental pathology. 2015;8(5):5363.
- 20. Charlier C, Kintz P, Dubois N, Plomteux G. Fatal overdosage with cisplatin. Journal of analytical toxicology. 2004;28(2):138-40.
- 21. Wen T, Song L, Hua S. Perspectives and controversies regarding the use of natural products for the treatment of lung cancer. Cancer Medicine. 2021;10(7):2396-422.
- 22. Chen Y-L, Lin S-Z, Chang J-Y, Cheng Y-L, Tsai N-M, Chen S-P, et al. In vitro and in vivo studies of a novel potential anticancer agent of isochaihulactone on human lung cancer A549 cells. Biochemical Pharmacology.
2006;72(3):308-19.
- 23. Li W-Y, Chan S-W, Guo D-J, Chung M-K, Leung T-Y, Yu PH-F. Water extract of Rheum officinale Baill. induces apoptosis in human lung adenocarcinoma A549 and human breast cancer MCF-7 cell lines. Journal of ethnopharmacology. 2009;124(2):251-6.
- 24. Hu W, Kavanagh JJ. Anticancer therapy targeting the apoptotic pathway. The lancet oncology. 2003;4(12):721-9.
- 25. Safarzadeh E, Shotorbani SS, Baradaran B. Herbal medicine as inducers of apoptosis in cancer treatment. Advanced pharmaceutical bulletin. 2014;4(Suppl 1):421.
- 26. Pan Z, Zhang X, Yu P, Chen X, Lu P, Li M, et al. Cinobufagin induces cell cycle arrest at the G2/M phase and promotes apoptosis in malignant melanoma cells. Frontiers in Oncology. 2019;9:853.
- 27. Stan SD, Zeng Y, Singh SV. Ayurvedic medicine constituent withaferin a causes G2 and M phase cell cycle arrest in human breast cancer cells. Nutrition and cancer. 2008;60(S1):51-60.
- 28. Sundarraj S, Thangam R, Sreevani V, Kaveri K, Gunasekaran P, Achiraman S, et al. γ-Sitosterol from Acacia nilotica L. induces G2/M cell cycle arrest and apoptosis through c-Myc suppression in MCF-7 and A549 cells. Journal of ethnopharmacology. 2012;141(3):803-9.
- 29. Zamble DB, Jacks T, Lippard SJ. p53-Dependent and-independent responses to cisplatin in mouse testicular teratocarcinoma cells. Proceedings of the National Academy of Sciences. 1998;95(11):6163-8.
- 30. Matsuda T, Kato T, Kiyotani K, Tarhan YE, Saloura V, Chung S, et al. p53-independent p21 induction by MELK inhibition. Oncotarget. 2017;8(35):57938.
- 31. Ho T, Tan BX, Lane D. How the other half lives: what p53 does when it is not being a transcription factor. International Journal of Molecular Sciences. 2019;21(1):13.
- 32. Tong Q-S, Zheng L-D, Wang L, Liu J, Qian W. BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells. BMC cancer. 2004;4(1):1-8.
- 33. Atagün G, Zafer E, ;Gürkanlı İ. Apoptoziste mitokondrinin rolü. Türk Bilimsel Derlemeler Dergisi. 2011(2):9-53.
- 34. Saxena M, Delgado Y, Sharma RK, Sharma S, Guzman SLPDL, Tinoco AD, et al. Inducing cell death in vitro in cancer cells by targeted delivery of cytochrome c via a transferrin conjugate. PLoS One. 2018;13(4):e0195542.
- 35. Roh JI, Lee J, Sung YH, Oh J, Hyeon DY, Kim Y, et al. Impaired AKT signaling and lung tumorigenesis by PIERCE1 ablation in KRAS-mutant non-small cell lung cancer. Oncogene. 2020;39(36):5876-87. Epub 2020/07/31. doi: 10.1038/s41388-020-01399-5. PubMed PMID: 32728173; PubMed Central PMCID: PMCPMC7471098.
- 36. Mologni L, Brussolo S, Ceccon M, Gambacorti-Passerini C. Synergistic effects of combined Wnt/KRAS inhibition in colorectal cancer cells. PloS one. 2012;7(12):e51449.
- 37. Bednarz-Misa I, Fortuna P, Diakowska D, Jamrozik N, Krzystek-Korpacka M. Distinct Local and Systemic Molecular Signatures in the Esophageal and Gastric Cancers: Possible Therapy Targets and Biomarkers for Gastric Cancer. Int J Mol Sci. 2020;21(12). Epub 2020/07/08. doi: 10.3390/ijms21124509. PubMed PMID: 32630408; PubMed Central PMCID: PMCPMC7349922.
- 38. Khosroushahi AY, Naderi-Manesh H, Yeganeh H, Barar J, Omidi Y. Novel water-soluble polyurethane nanomicelles for cancer chemotherapy: physicochemical characterization and cellular activities. J Nanobiotechnology. 2012;10:2. Epub 2012/01/10. doi: 10.1186/1477-3155-10-2. PubMed PMID: 22221539; PubMed Central PMCID: PMCPMC3286383.
- 39. Wu Q, Zhang H, Yang D, Min Q, Wang Y, Zhang W, et al. The m6A-induced lncRNA CASC8 promotes proliferation and chemoresistance via upregulation of hnRNPL in esophageal squamous cell carcinoma. International Journal of Biological Sciences. 2022;18(13):4824-36.