The cytotoxic and apoptotic effects of $\textit{Abies nordmanniana subsp. bornmülleriana Mattf }$ resin extract on prostate cancer cell cells

Year 2023, Volume: 32 Issue: 2, 119 - 136, 30.12.2023

Muhammet Burak Batir , Sevinç Batır , Feyzan Ozdal Kurt , Sırrı Çam

https://doi.org/10.53447/communc.1272043

Abstract

Cancer has become one of the most critical health issues, with an increasing incidence and mortality in recent years. Meanwhile, many studies are carried out on discovering new compounds which reflects effective results on cancer cells. Therefore, this study aimed to examine the cytotoxic, anti-proliferative and apoptotic effects on cancer cell lines by using the extract obtained from Uludağ Fir ($\textit{Abies nordmanniana subsp. bornmülleriana Mattf }$) resin. Uludağ Fir resin extract was obtained by applying the methanol extraction method. In our study, fibroblast cell L-929, human metastatic prostate cancer PC-3 and human metastatic prostate cancer DU-145 cell lines were cultured in RPMI-1640 medium. The effects of the resin extract concentrations on the viability of the cells were determined with the Muse™ Cell Count & Viability test. In addition, apoptosis and cell cycle phases of the cells were determined using the Muse™ cell analyzer. Finally, RT-qPCR analysis was performed to determine the resin extract effect on pro-apoptotic and anti-apoptotic gene expression. The apoptotic effect of Uludağ Fir resin extract on cancer cell lines was significantly higher in contrast to the healthy normal cells. In addition, it was determined that Uludağ Fir extract caused G0/G1 cell cycle arrest in cancer cells. In RT-qPCR analysis, the pro-apoptotic gene expression levels were apparently increased in cancer cells, which was followed by a decrease in the anti-apoptotic gene expression levels. All taken together, these results indicate that Uludağ Fir resin extract exerts two prong effects as it induces a cell cycle arrest and apoptotic pathway activation on human prostate cancer cell lines.

Keywords

Prostate cancer, Uludağ Fir, cell viability, apoptosis, cell cyle arrest

Supporting Institution

Scientific Investigation Department of Manisa Celal Bayar University

Project Number

2021-080

Thanks

This research was financially supported by the Scientific Investigation Department of Manisa Celal Bayar University (project number 2021-080).

References

• Blagosklonny, M.V., Hallmarks of cancer and hallmarks of aging. Aging, 14 (9) (2022), 4176-4187. https://doi.org/10.18632/aging.204082.
• Chang, A.J., Autio, K.A., Roach, M., Scher, H.I., High-risk prostate cancer-classification and therapy. Nature Reviews Clinical Oncology, 11 (6) (2014), 308–323. https://doi.org/10.1038/nrclinonc.2014.68.
• Di Martile, M., Garzoli, S., Ragno, R., Del Bufalo, D., Essential oils and their main chemical components: The past 20 years of preclinical studies in melanoma. Cancers, 12 (9) (2020), 2650. https://doi.org/10.3390/cancers12092650.
• Cao, Y., Li, H., Harmony between humanity and nature: natural vs. synthetic drug preference in Chinese atheists and taoists. Journal of Religion and Health, 61 (4) (2022), 2743–2752. https://doi.org/10.1007/s10943-021-01314-6.
• Luethi, D., Liechti, M.E., Designer drugs: mechanism of action and adverse effects. Archives of Toxicology, 94 (4) (2020), 1085–1133. https://doi.org/10.1007/s00204-020-02693-7.
• Vaghari-Tabari, M., Hassanpour, P., Sadeghsoltani, F., Malakoti, F., Alemi, F., Qujeq, D., Asemi, Z., Yousefi, B., CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer. Cellular & Molecular Biology Letters, 27 (1) (2022), 49. https://doi.org/10.1186/s11658-022-00348-2.
• Xavier, C.P.R., Caires, H.R., Barbosa, M.A.G., Bergantim, R., Guimarães, J.E., & Vasconcelos, M.H., The role of extracellular vesicles in the hallmarks of cancer and drug resistance. Cells, 9 (5) (2020), 1141. https://doi.org/10.3390/cells9051141.
• Martínez Andrade, K. A., Lauritano, C., Romano, G., Ianora, A., Marine microalgae with anti-cancer properties. Marine Drugs, 16 (5) (2018), 165. https://doi.org/10.3390/md16050165.
• Saadaoui, I., Rasheed, R., Abdulrahman, N., Bounnit, T., Cherif, M., Al Jabri, H., Mraiche, F., Algae-derived bioactive compounds with anti-lung cancer potential. Marine Drugs, 18 (4) (2020), 197. https://doi.org/10.3390/md18040197.
• Fitsiou, E., Pappa, A., Anticancer activity of essential oils and other extracts from aromatic plants grown in Greece. Antioxidants, 8 (8) (2019), 290. https://doi.org/10.3390/antiox8080290.
• Elansary, H. O., Abdelgaleil, S. A. M., Mahmoud, E. A., Yessoufou, K., Elhindi, K., El-Hendawy, S., Effective antioxidant, antimicrobial and anticancer activities of essential oils of horticultural aromatic crops in northern Egypt. BMC Complementary and Alternative Medicine, 18 (1) (2018), 214. https://doi.org/10.1186/s12906-018-2262-1.
• Zuzarte, M., Francisco, V., Neves, B., Liberal, J., Cavaleiro, C., Canhoto, J., Salgueiro, L., Cruz, M.T., Lavandula viridis L´Hér. Essential oil inhibits the inflammatory response in macrophages through blockade of NF-KB signaling cascade. Frontiers in Pharmacology, 12 (2022), 695911. https://doi.org/10.3389/fphar.2021.695911.
• Walia, M., Mann, T.S., Kumar, D., Agnihotri, V.K., Singh, B., Chemical composition and in vitro cytotoxic activity of essential oil of leaves of Malus domestica growing in Western Himalaya (India). Evidence-based Complementary and Alternative Medicine, eCAM, 2012, 649727. https://doi.org/10.1155/2012/649727.
• Thalappil, M.A., Butturini, E., Carcereri de Prati, A., Bettin, I., Antonini, L., Sapienza, F.U., Garzoli, S., Ragno, R., Mariotto, S., Pinus mugo essential oil impairs STAT3 activation through oxidative stress and induces apoptosis in prostate cancer cells. Molecules, 27 (15) (2022), 4834. https://doi.org/10.3390/molecules27154834.
• Legault, J., Dahl, W., Debiton, E., Pichette, A., Madelmont, J.C., Antitumor activity of balsam fir oil: production of reactive oxygen species induced by alpha-humulene as possible mechanism of action. Planta Medica, 69 (5) (2003), 402–407. https://doi.org/10.1055/s-2003-39695.
• Uçar, S.E, Şahin, B.S., Ulu, M., Akpolat, A., The determination of in vitro antioxidant and cytotoxic activities of resin obtained from Cilician Fir (Abies cilicica (Antoine & Kotschy) Carrière). Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi, 23 (6) (2020), 1503-1509. https://doi.org/10.18016/ksutarimdoga.vi.720675.
• Kudryavtseva, A., Krasnov, G., Lipatova, A., Alekseev, B., Maganova, F., Shaposhnikov, M., Fedorova, M., Snezhkina, A., Moskalev, A., Effects of Abies sibirica terpenes on cancer- and aging-associated pathways in human cells. Oncotarget, 7 (50) (2016), 83744–83754. https://doi.org/10.18632/oncotarget.13467.
• Anşin, R., Özkan, Z., Abies Mill. Göknarlar, Tohumlu Bitkiler (Spermatophyta), Odunsu Taksonlar, Karadeniz Teknik Üniversitesi, Orman Fakültesi. Trabzon. 167, 19 (1997), 66-72.
• Oztatlici, H., Oztatlici, M., Daglı, S. N., Karadeniz Saygili, S., Bir sefalosporin olan sefepim, nb2a nöroblastoma hücrelerinde apoptozu ve oksidatif stresi indükler. Euroasia Journal of Mathematics, Engineering, Natural & Medical Sciences, 9 (21) (2022), 79–86. https://doi.org/10.38065/euroasiaorg.962.
• Livak, K. J., Schmittgen, T. D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25 (4) (2001), 402–408. https://doi.org/10.1006/meth.2001.1262.
• Lin, L., Zhang, M. X., Zhang, L., Zhang, D., Li, C., Li, Y. L., Autophagy, pyroptosis, and ferroptosis: New regulatory mechanisms for atherosclerosis. Frontiers in Cell and Developmental Biology, 9 (2022), 809955. https://doi.org/10.3389/fcell.2021.809955.
• Zhao, J., Jiang, P., Guo, S., Schrodi, S. J., He, D., Apoptosis, autophagy, NETosis, necroptosis, and pyroptosis mediated programmed cell death as targets for innovative therapy in Rheumatoid Arthritis. Frontiers in Immunology, 12 (2021), 809806. https://doi.org/10.3389/fimmu.2021.809806.
• Bertheloot, D., Latz, E., Franklin, B.S., Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cellular & Molecular Immunology, 18 (5) (2021), 106-1121. https://doi.org/10.1038/s41423-020-00630-3.
• Trang, D.T., Hoang, T.K.V., Nguyen, T.T.M., Van Cuong, P., Dang, N.H., Dang, H.D., Nguyen Quang, T., Dat, N.T., Essential oils of lemongrass (Cymbopogon citratus Stapf) induces apoptosis and cell cycle arrest in A549 lung cancer cells. BioMed research international, (2020), 5924856. https://doi.org/10.1155/2020/5924856.
• Chung, K. S., Hong, J. Y., Lee, J. H., Lee, H. J., Park, J. Y., Choi, J. H., Park, H. J., Hong, J., Lee, K. T., β-Caryophyllene in the essential oil from Chrysanthemum Boreale induces G1 phase cell cycle arrest in human lung cancer cells. Molecules, 24 (20) (2019), 3754. https://doi.org/10.3390/molecules24203754.
• Seal, S., Chatterjee, P., Bhattacharya, S., Pal, D., Dasgupta, S., Kundu, R., Mukherjee, S., Bhattacharya, S., Bhuyan, M., Bhattacharyya, P. R., Baishya, G., Barua, N. C., Baruah, P. K., Rao, P. G., Bhattacharya, S., Vapor of volatile oils from Litsea cubeba seed induces apoptosis and causes cell cycle arrest in lung cancer cells. PloS One, 7 (10) (2012), e47014.4 https://doi.org/10.1371/journal.pone.0047014.
• Salehi, B., Upadhyay, S., Erdogan Orhan, I., Kumar Jugran, A., L D Jayaweera, S., A Dias, D., Sharopov, F., Taheri, Y., Martins, N., Baghalpour, N., Cho, W. C., Sharifi-Rad, J., Therapeutic potential of α- and β-Pinene: A miracle gift of nature. Biomolecules, 9 (11) (2019), 738. https://doi.org/10.3390/biom9110738.
• Li Y, Gao Y, Deng L, Lian H, Guo W, Wu W, Xue B, Li B, Su Y, Zhang H. Volatile profiling and transcriptome sequencing provide insights into the biosynthesis of α-pinene and β-pinene in Liquidambar formosana hance leaves. Genes, 14 (1) 163. https://doi.org/10.3390/genes14010163.
• Chebet, J. J., Ehiri, J. E., McClelland, D. J., Taren, D., Hakim, I. A., Effect of d-limonene and its derivatives on breast cancer in human trials: a scoping review and narrative synthesis. BMC cancer, 21 (1) (2021) 902. https://doi.org/10.1186/s12885-021-08639-1.
• Alipanah, H., Farjam, M., Zarenezhad, E., Roozitalab, G., Osanloo, M., Chitosan nanoparticles containing limonene and limonene-rich essential oils: potential phytotherapy agents for the treatment of melanoma and breast cancers. BMC Complementary Medicine and Therapies, 21 (1) (2021), 186. https://doi.org/10.1186/s12906-021-03362-7.
• Hou, J., Zhang, Y., Zhu, Y., Zhou, B., Ren, C., Liang, S., Guo, Y., α-Pinene induces apoptotic cell death via caspase activation in human ovarian cancer cells. Medical Science Monitor, 25 (2019), 6631–6638. https://doi.org/10.12659/MSM.916419.