Research Article
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Year 2025, Volume: 34 Issue: SI, 46 - 57

Muhammet Burak Batır , Sevinc Batır , Fatma Goral Sibel Alkan Tan Fethi Sırrı Cam , Feyzan Ozdal Kurt

https://doi.org/10.38042/biotechstudies.1672789

Abstract

Project Number

FEF 2023-077

References

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  • Abo-Elghiet, F., Ibrahim, M. H., El Hassab, M. A., Bader, A., Abdallah, Q. M. A., & Temraz, A. (2022). LC/MS analysis of Viscum cruciatum Sieber ex Boiss. extract with anti-proliferative activity against MCF-7 cell line via G0/G1 cell cycle arrest: An in-silico and in-vitro study. Journal of ethnopharmacology, 295, 115439. https://doi.org/10.1016/j.jep.2022.115439
  • Alam, M. A., Quamri, M. A., Ayman, U., Sofi, G., & Renuka, B. N. (2021). Understanding Humma-e-Wabai (epidemic fever) and Amraz-e-Wabai (epidemic disease) in the light of Unani medicine. Journal of complementary & integrative medicine, 18(3), 469–476. https://doi.org/10.1515/jcim-2020-0124
  • Atanasov, A. G., Zotchev, S. B., Dirsch, V. M., International Natural Product Sciences Taskforce, & Supuran, C. T. (2021). Natural products in drug discovery: advances and opportunities. Nature reviews. Drug discovery, 20(3), 200–216. https://doi.org/10.1038/s41573-020-00114-z
  • Aziz, M.Y.A., Johari, S.A.T.T., Mamat, W.N.A.W., Taib, W.R.W., Othman, A.S., & Rohin, M.A.K. (2023) Cytotoxic Activity of Ethanolic Extract Aquilaria malaccensis Leaves Against MCF-7 Cells. Malaysian Journal of Medicine & Health Sciences, 19 (6), p215. https://doi.org/10.47836/mjmhs.19.6.29
  • Batır, M. B., Şahin, E., & Çam, F. S. (2019). Evaluation of the CRISPR/Cas9 directed mutant TP53 gene repairing effect in human prostate cancer cell line PC-3. Molecular biology reports, 46(6), 6471–6484. https://doi.org/10.1007/s11033-019-05093-y
  • Batir MB., Batir S., Ozdal Kurt F., & Çam S. (2023) The cytotoxic and apoptotic effects of Abies nordmanniana subsp. bornmülleriana Mattf resin extract on prostate cancer cell cells. Communications Faculty of Sciences University of Ankara Series C Biology. 2023;32(2):119-36. https://doi.org/10.53447/communc.1272043
  • Bertheloot, D., Latz, E., & Franklin, B. S. (2021). Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cellular & molecular immunology, 18(5), 1106–1121. https://doi.org/10.1038/s41423-020-00630-3
  • Carneiro, B. A., & El-Deiry, W. S. (2020). Targeting apoptosis in cancer therapy. Nature reviews. Clinical oncology, 17(7), 395–417. https://doi.org/10.1038/s41571-020-0341-y
  • Chakrabarti, G., Gerber, D. E., & Boothman, D. A. (2015). Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways. Clinical pharmacology : advances and applications, 7, 57–68. https://doi.org/10.2147/CPAA.S79760
  • Chaudhry, G. E., Md Akim, A., Sung, Y. Y., & Sifzizul, T. M. T. (2022). Cancer and apoptosis: The apoptotic activity of plant and marine natural products and their potential as targeted cancer therapeutics. Frontiers in pharmacology, 13, 842376. https://doi.org/10.3389/fphar.2022.842376
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  • Harvey, A. L., Edrada-Ebel, R., & Quinn, R. J. (2015). The re-emergence of natural products for drug discovery in the genomics era. Nature reviews. Drug discovery, 14(2), 111–129. https://doi.org/10.1038/nrd4510
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  • Kundishora, A., Sithole, S., & Mukanganyama, S. (2020). Determination of the Cytotoxic Effect of Different Leaf Extracts from Parinari curatellifolia (Chrysobalanaceae). Journal of toxicology, 2020, 8831545. https://doi.org/10.1155/2020/8831545
  • Lawson, A. D. G., MacCoss, M., & Heer, J. P. (2018). Importance of Rigidity in Designing Small Molecule Drugs To Tackle Protein-Protein Interactions (PPIs) through Stabilization of Desired Conformers. Journal of medicinal chemistry, 61(10), 4283–4289. https://doi.org/10.1021/acs.jmedchem.7b01120
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  • Li, K., Zheng, Q., Chen, X., Wang, Y., Wang, D., & Wang, J. (2018). Isobavachalcone Induces ROS-Mediated Apoptosis via Targeting Thioredoxin Reductase 1 in Human Prostate Cancer PC-3 Cells. Oxidative medicine and cellular longevity, 2018, 1915828. https://doi.org/10.1155/2018/1915828
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  • Li, A. X., Sun, M., & Li, X. (2017). Withaferin-A induces apoptosis in osteosarcoma U2OS cell line via generation of ROS and disruption of mitochondrial membrane potential. European review for medical and pharmacological sciences, 21(6), 1368–1374.
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  • Luna-López, A., Triana-Martínez, F., López-Diazguerrero, N. E., Ventura-Gallegos, J. L., Gutiérrez-Ruiz, M. C., Damián-Matsumura, P., Zentella, A., Gómez-Quiroz, L. E., & Königsberg, M. (2010). Bcl-2 sustains hormetic response by inducing Nrf-2 nuclear translocation in L929 mouse fibroblasts. Free radical biology & medicine, 49(7), 1192–1204. https://doi.org/10.1016/j.freeradbiomed.2010.07.004
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  • Perillo, B., Di Donato, M., Pezone, A., Di Zazzo, E., Giovannelli, P., Galasso, G., Castoria, G., & Migliaccio, A. (2020). ROS in cancer therapy: the bright side of the moon. Experimental & molecular medicine, 52(2), 192–203. https://doi.org/10.1038/s12276-020-0384-2
  • Prasad, S. K., Veeresh, P. M., Ramesh, P. S., Natraj, S. M., Madhunapantula, S. V., & Devegowda, D. (2020). Phytochemical fractions from Annona muricata seeds and fruit pulp inhibited the growth of breast cancer cells through cell cycle arrest at G0/G1 phase. Journal of cancer research and therapeutics, 16(6), 1235–1249.https://doi.org/10.4103/jcrt.JCRT_494_19
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  • Rajabi, S., Maresca, M., Yumashev, A. V., Choopani, R., & Hajimehdipoor, H. (2021). The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy. Biomolecules, 11(4), 534. https://doi.org/10.3390/biom11040534
  • Samson, F. E., & Nelson, S. R. (2000). The aging brain, metals and oxygen free radicals. Cellular and molecular biology (Noisy-le-Grand, France), 46(4), 699–707.
  • Sidhu, P., Shankargouda, S., Rath, A., Hesarghatta Ramamurthy, P., Fernandes, B., & Kumar Singh, A. (2020). Therapeutic benefits of liquorice in dentistry. Journal of Ayurveda and integrative medicine, 11(1), 82–88. https://doi.org/10.1016/j.jaim.2017.12.004
  • Solowey, E., Lichtenstein, M., Sallon, S., Paavilainen, H., Solowey, E., & Lorberboum-Galski, H. (2014). Evaluating medicinal plants for anticancer activity. TheScientificWorldJournal, 2014, 721402. https://doi.org/10.1155/2014/721402
  • Sytar, O., & Smetanska, I. (2022). Special Issue "Bioactive Compounds from Natural Sources (2020, 2021)". Molecules (Basel, Switzerland), 27(6), 1929. https://doi.org/10.3390/molecules27061929
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Cytotoxic activity of methanolic and ethanolic extract of Aquilaria agallocha Roxb. heartwood against healthy fibroblast and breast cancer cells

Year 2025, Volume: 34 Issue: SI, 46 - 57

Muhammet Burak Batır , Sevinc Batır , Fatma Goral Sibel Alkan Tan Fethi Sırrı Cam , Feyzan Ozdal Kurt

https://doi.org/10.38042/biotechstudies.1672789

Abstract

Aquilaria agallocha Roxb. has traditionally been used to treat various medical conditions, including inflammation, fever, and cardioprotection. However, limited studies have explored its specific effects on cancer cells while distinguishing its impact on normal cells. This study aimed to evaluate the effects of A. agallocha heartwood extracts on both normal and cancer cells. To achieve this, mouse L929 (normal), 67NR, and 4T1 (cancer) cells were treated with methanol and ethanol extracts of A. agallocha heartwood to assess cytotoxicity, apoptosis, and oxidative stress. Flow cytometry analysis revealed that both extracts induced apoptosis and oxidative stress in all tested cell lines. However, the extracts exhibited a greater cytotoxic effect on normal L929 cells, potentially due to their bioactive components exerting a stronger pro-oxidant effect. These findings suggest that A. agallocha extracts may differentially affect normal and cancer cells, highlighting the need for further investigation into their selective cytotoxicity.

Keywords

Aquilaria agallocha Roxb Breast cancer Apoptosis Oxidative stress

Supporting Institution

Funding This research was financially supported by the Scientific Investigation Department of Manisa Celal Bayar University with the project number FEF 2023-077.

Project Number

FEF 2023-077

Thanks

This research was fnancially supported by the Scientific Investigation Department of Manisa Celal Bayar University with the project number 2023-077.

References

  • Abbas P., Hashım Yzh., & Salleh Hm. (2019) Uninfected agarwood branch extract possess cytotoxic and inhibitory effects on MCF-7 breast cancer cells. J.Res.Pharm.; 23(1): 120-129. http://dx.doi.org/10.12991/jrp.2018.116
  • Abo-Elghiet, F., Ibrahim, M. H., El Hassab, M. A., Bader, A., Abdallah, Q. M. A., & Temraz, A. (2022). LC/MS analysis of Viscum cruciatum Sieber ex Boiss. extract with anti-proliferative activity against MCF-7 cell line via G0/G1 cell cycle arrest: An in-silico and in-vitro study. Journal of ethnopharmacology, 295, 115439. https://doi.org/10.1016/j.jep.2022.115439
  • Alam, M. A., Quamri, M. A., Ayman, U., Sofi, G., & Renuka, B. N. (2021). Understanding Humma-e-Wabai (epidemic fever) and Amraz-e-Wabai (epidemic disease) in the light of Unani medicine. Journal of complementary & integrative medicine, 18(3), 469–476. https://doi.org/10.1515/jcim-2020-0124
  • Atanasov, A. G., Zotchev, S. B., Dirsch, V. M., International Natural Product Sciences Taskforce, & Supuran, C. T. (2021). Natural products in drug discovery: advances and opportunities. Nature reviews. Drug discovery, 20(3), 200–216. https://doi.org/10.1038/s41573-020-00114-z
  • Aziz, M.Y.A., Johari, S.A.T.T., Mamat, W.N.A.W., Taib, W.R.W., Othman, A.S., & Rohin, M.A.K. (2023) Cytotoxic Activity of Ethanolic Extract Aquilaria malaccensis Leaves Against MCF-7 Cells. Malaysian Journal of Medicine & Health Sciences, 19 (6), p215. https://doi.org/10.47836/mjmhs.19.6.29
  • Batır, M. B., Şahin, E., & Çam, F. S. (2019). Evaluation of the CRISPR/Cas9 directed mutant TP53 gene repairing effect in human prostate cancer cell line PC-3. Molecular biology reports, 46(6), 6471–6484. https://doi.org/10.1007/s11033-019-05093-y
  • Batir MB., Batir S., Ozdal Kurt F., & Çam S. (2023) The cytotoxic and apoptotic effects of Abies nordmanniana subsp. bornmülleriana Mattf resin extract on prostate cancer cell cells. Communications Faculty of Sciences University of Ankara Series C Biology. 2023;32(2):119-36. https://doi.org/10.53447/communc.1272043
  • Bertheloot, D., Latz, E., & Franklin, B. S. (2021). Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cellular & molecular immunology, 18(5), 1106–1121. https://doi.org/10.1038/s41423-020-00630-3
  • Carneiro, B. A., & El-Deiry, W. S. (2020). Targeting apoptosis in cancer therapy. Nature reviews. Clinical oncology, 17(7), 395–417. https://doi.org/10.1038/s41571-020-0341-y
  • Chakrabarti, G., Gerber, D. E., & Boothman, D. A. (2015). Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways. Clinical pharmacology : advances and applications, 7, 57–68. https://doi.org/10.2147/CPAA.S79760
  • Chaudhry, G. E., Md Akim, A., Sung, Y. Y., & Sifzizul, T. M. T. (2022). Cancer and apoptosis: The apoptotic activity of plant and marine natural products and their potential as targeted cancer therapeutics. Frontiers in pharmacology, 13, 842376. https://doi.org/10.3389/fphar.2022.842376
  • Clardy, J., & Walsh, C. (2004). Lessons from natural molecules. Nature, 432(7019), 829–837. https://doi.org/10.1038/nature03194
  • Dahham S. S., Ahamed M. B. K., Saghir S. M., Alsuede F. S., Iqbal M. A., & Majid A. (2014) Bioactive essential oils from Aquilaria crassna for cancer prevention and treatment. GJPAAS, 4, 26–31. https://doi.org/10.13140/2.1.3315.7125
  • Doak, B. C., Over, B., Giordanetto, F., & Kihlberg, J. (2014). Oral druggable space beyond the rule of 5: insights from drugs and clinical candidates. Chemistry & biology, 21(9), 1115–1142. https://doi.org/10.1016/j.chembiol.2014.08.013
  • Feher, M., & Schmidt, J. M. (2003). Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry. Journal of chemical information and computer sciences, 43(1), 218–227. https://doi.org/10.1021/ci0200467
  • Guo, H., Yang, Y., Lou, Y., Zuo, Z., Cui, H., Deng, H., Zhu, Y., & Fang, J. (2023). Apoptosis and DNA damage mediated by ROS involved in male reproductive toxicity in mice induced by Nickel. Ecotoxicology and environmental safety, 268, 115679. https://doi.org/10.1016/j.ecoenv.2023.115679
  • Harvey, A. L., Edrada-Ebel, R., & Quinn, R. J. (2015). The re-emergence of natural products for drug discovery in the genomics era. Nature reviews. Drug discovery, 14(2), 111–129. https://doi.org/10.1038/nrd4510
  • Kashyap, D., Garg, V. K., & Goel, N. (2021). Intrinsic and extrinsic pathways of apoptosis: Role in cancer development and prognosis. Advances in protein chemistry and structural biology, 125, 73–120. https://doi.org/10.1016/bs.apcsb.2021.01.003
  • Ketelut-Carneiro, N., & Fitzgerald, K. A. (2022). Apoptosis, Pyroptosis, and Necroptosis-Oh My! The Many Ways a Cell Can Die. Journal of molecular biology, 434(4), 167378. https://doi.org/10.1016/j.jmb.2021.167378
  • Kundishora, A., Sithole, S., & Mukanganyama, S. (2020). Determination of the Cytotoxic Effect of Different Leaf Extracts from Parinari curatellifolia (Chrysobalanaceae). Journal of toxicology, 2020, 8831545. https://doi.org/10.1155/2020/8831545
  • Lawson, A. D. G., MacCoss, M., & Heer, J. P. (2018). Importance of Rigidity in Designing Small Molecule Drugs To Tackle Protein-Protein Interactions (PPIs) through Stabilization of Desired Conformers. Journal of medicinal chemistry, 61(10), 4283–4289. https://doi.org/10.1021/acs.jmedchem.7b01120
  • Lee, S. O., Joo, S. H., Kwak, A. W., Lee, M. H., Seo, J. H., Cho, S. S., Yoon, G., Chae, J. I., & Shim, J. H. (2021). Podophyllotoxin Induces ROS-Mediated Apoptosis and Cell Cycle Arrest in Human Colorectal Cancer Cells via p38 MAPK Signaling. Biomolecules & therapeutics, 29(6), 658–666. https://doi.org/10.4062/biomolther.2021.143
  • Li, K., Zheng, Q., Chen, X., Wang, Y., Wang, D., & Wang, J. (2018). Isobavachalcone Induces ROS-Mediated Apoptosis via Targeting Thioredoxin Reductase 1 in Human Prostate Cancer PC-3 Cells. Oxidative medicine and cellular longevity, 2018, 1915828. https://doi.org/10.1155/2018/1915828
  • Li, X., Chen, Y., Zhao, J., Shi, J., Wang, M., Qiu, S., Hu, Y., Xu, Y., Cui, Y., Liu, C., & Liu, C. (2019). The Specific Inhibition of SOD1 Selectively Promotes Apoptosis of Cancer Cells via Regulation of the ROS Signaling Network. Oxidative medicine and cellular longevity, 2019, 9706792. https://doi.org/10.1155/2019/9706792
  • Li, A. X., Sun, M., & Li, X. (2017). Withaferin-A induces apoptosis in osteosarcoma U2OS cell line via generation of ROS and disruption of mitochondrial membrane potential. European review for medical and pharmacological sciences, 21(6), 1368–1374.
  • Limam, I., Ghali, R., Abdelkarim, M., Ouni, A., Araoud, M., Abdelkarim, M., Hedhili, A., & Ben-Aissa Fennira, F. (2024). Tunisian Artemisia campestris L.: a potential therapeutic agent against myeloma - phytochemical and pharmacological insights. Plant methods, 20(1), 59. https://doi.org/10.1186/s13007-024-01185-4
  • Luna-López, A., Triana-Martínez, F., López-Diazguerrero, N. E., Ventura-Gallegos, J. L., Gutiérrez-Ruiz, M. C., Damián-Matsumura, P., Zentella, A., Gómez-Quiroz, L. E., & Königsberg, M. (2010). Bcl-2 sustains hormetic response by inducing Nrf-2 nuclear translocation in L929 mouse fibroblasts. Free radical biology & medicine, 49(7), 1192–1204. https://doi.org/10.1016/j.freeradbiomed.2010.07.004
  • Nahar, J., Boopathi, V., Rupa, E. J., Awais, M., Valappil, A. K., Morshed, M. N., Murugesan, M., Akter, R., Yang, D. U., Mathiyalagan, R. (2023) Protective Effects of Aquilaria agallocha and Aquilaria malaccensis Edible Plant Extracts against Lung Cancer, Inflammation, and Oxidative Stress—In Silico and In Vitro Study. Applied Sciences, 13(10):6321. https://doi.org/10.3390/app13106321
  • Newman, D. J., & Cragg, G. M. (2016). Natural Products as Sources of New Drugs from 1981 to 2014. Journal of natural products, 79(3), 629–661. https://doi.org/10.1021/acs.jnatprod.5b01055
  • Nguyen, T. T. T., Pham, T. N. M., Nguyen, C. T. N., Truong, T. N., Bishop, C., Doan, N. Q. H., & Le, T. H. V. (2023). Phytochemistry and Cytotoxic Activity of Aquilaria crassna Pericarp on MDA-MB-468 Cell Lines. ACS omega, 8(45), 42356–42366. https://doi.org/10.1021/acsomega.3c04656
  • Jaramillo-Rangel, G., Chávez-Briones, M. D., Niderhauser-García, A., & Ortega-Martínez, M. (2020). Toxicity and Anticancer Potential of Karwinskia: A Review. Molecules (Basel, Switzerland), 25(23), 5590.https://doi.org/10.3390/molecules25235590
  • Perillo, B., Di Donato, M., Pezone, A., Di Zazzo, E., Giovannelli, P., Galasso, G., Castoria, G., & Migliaccio, A. (2020). ROS in cancer therapy: the bright side of the moon. Experimental & molecular medicine, 52(2), 192–203. https://doi.org/10.1038/s12276-020-0384-2
  • Prasad, S. K., Veeresh, P. M., Ramesh, P. S., Natraj, S. M., Madhunapantula, S. V., & Devegowda, D. (2020). Phytochemical fractions from Annona muricata seeds and fruit pulp inhibited the growth of breast cancer cells through cell cycle arrest at G0/G1 phase. Journal of cancer research and therapeutics, 16(6), 1235–1249.https://doi.org/10.4103/jcrt.JCRT_494_19
  • Raheel R., Saddiqe Z., Iram M., & Afzal S. (2017) In vitro antimitotic, antiproliferative and antioxidant activity of stem bark extracts of Ficus benghalensis L., South African Journal of Botany, Volume 111, Pages 248-257. https://doi.org/10.1016/j.sajb.2017.03.037
  • Rajabi, S., Maresca, M., Yumashev, A. V., Choopani, R., & Hajimehdipoor, H. (2021). The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy. Biomolecules, 11(4), 534. https://doi.org/10.3390/biom11040534
  • Samson, F. E., & Nelson, S. R. (2000). The aging brain, metals and oxygen free radicals. Cellular and molecular biology (Noisy-le-Grand, France), 46(4), 699–707.
  • Sidhu, P., Shankargouda, S., Rath, A., Hesarghatta Ramamurthy, P., Fernandes, B., & Kumar Singh, A. (2020). Therapeutic benefits of liquorice in dentistry. Journal of Ayurveda and integrative medicine, 11(1), 82–88. https://doi.org/10.1016/j.jaim.2017.12.004
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There are 42 citations in total.

Details

Primary Language English
Subjects Cell Metabolism, Gene Expression
Journal Section Research Articles
Authors

Muhammet Burak Batır 0000-0002-8722-5055

Sevinc Batır 0000-0003-1817-3113

Fatma Goral 0009-0007-9154-5872

Sibel Alkan Tan 0009-0002-5415-6708

Fethi Sırrı Cam 0000-0002-0972-8896

Feyzan Ozdal Kurt 0000-0001-6070-3742

Project Number FEF 2023-077
Early Pub Date April 9, 2025
Publication Date
Submission Date August 11, 2024
Acceptance Date April 8, 2025
Published in Issue Year 2025 Volume: 34 Issue: SI

Cite

APA Batır, M. B., Batır, S., Goral, F., Alkan Tan, S., et al. (2025). Cytotoxic activity of methanolic and ethanolic extract of Aquilaria agallocha Roxb. heartwood against healthy fibroblast and breast cancer cells. Biotech Studies, 34(SI), 46-57. https://doi.org/10.38042/biotechstudies.1672789


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