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Lycopodium clavatum ekstraktının SKBR-3 insan meme kanseri hücreleri üzerindeki apoptotik etkileri

Year 2023, Volume: 48 Issue: 4, 1207 - 1216, 29.12.2023
https://doi.org/10.17826/cumj.1336606

Abstract

Amaç: Meme kanseri dünya çapında önemli bir halk sağlığı sorunudur. Bitkisel kaynaklı doğal bileşikler, düşük toksisiteleri, güvenilirlikleri ve potansiyel etkinlikleri nedeniyle kanserle mücadelede umut verici adaylar olarak kabul edilmektedir. Bu çalışmada, Lycopodium clavatum'un etanol ekstraktının SKBR-3 insan meme kanseri hücreleri üzerindeki apoptotik etkisi araştırılmıştır.
Gereç ve Yöntem: İnsan meme kanseri hücrelerinin canlılığını değerlendirmek için farklı dozlarda (100, 200 ve 300 µg/mL) ve sürelerde (12, 24 ve 48 saat) Lycopodium clavatum etanol ekstraktı uygulamasının etkisi, WST-1 sitotoksisite testi kullanılarak incelenmiştir. Ayrıca, Lycopodium clavatum etanol ekstraktının apoptoz mekanizması, içsel (BAX ve Kaspaz-9) ve dışsal (Kaspaz-8 ve Kaspaz-3) yolaklar ile araştırılmıştır.
Bulgular: Lycopodium clavatum etanol ekstraktı uygulaması SKBR-3 hücrelerinde bu etkinin uygulanan doz ve tedavi süresine bağlı olarak sitotoksik bir etki göstermiştir. LC-EE ile 12 saatlik inkübasyondan sonra kontrol grubuna kıyasla; 100 µg/mL verilen grupta %10, 200 µg/mL verilen grupta %25, 300 µg/mL verilen grupta %40’lık bir hücre ölümü gözlenmiştir. Ayrıca, yapılan gözlemler Lycopodium clavatum tedavisinin BAX, Kaspaz-9, Kaspaz-8 ve Kaspaz-3 gibi apoptozla ilişkili proteinlerin aktivasyonunu tetiklediğini göstermektedir.
Sonuç: Lycopodium clavatum etanol ekstraktının SKBR-3 hücrelerinde anti-kanser etkisini içsel ve dışsal apoptotik yolları aktive ederek gerçekleştirebileceğini ortaya koymuştur. Bu bulgular, Lycopodium clavatum'un insan meme kanserine karşı etkili bir anti-kanser ajanı olarak yeni terapötik stratejilerin geliştirilmesine yardımcı olabileceğini göstermektedir.

Project Number

1919B012217673

References

  • Azamjah N, Soltan-Zadeh Y, Zayeri F. Global trend of breast cancer mortality rate: a 25-year study. Asian Pac J Cancer Prev. 2019;20:2015-2020.
  • Naeem M, Iqbal MO, Khan H, Ahmed MM, Farooq M, Aadil MM, et al. A review of twenty years of research on the regulation of signaling pathways by natural products in breast cancer. Molecules. 2022;27:3412.
  • Das S, Das J, Samadder A, Boujedaini N, Khuda-Bukhsh AR. Apigenin-induced apoptosis in A375 and A549 cells through selective action and dysfunction of mitochondria. Exp Biol Med. 2012;237:1433-48.
  • Banerjee JN, Biswas S, Madhu NR, Karmakar SR, Biswas SJ. A better understanding of pharmacological activities and uses of phytochemicals of Lycopodium clavatum: A review. J Pharmacogn Phytochem. 2014;3:207-10.
  • Mandal SK, Biswas R, Bhattacharyya SS, Paul S, Dutta S, Pathak S, et al. Lycopodine from Lycopodium clavatum extract inhibits proliferation of HeLa cells through induction of apoptosis via caspase-3 activation. Eur J Pharmacol. 2010;626:115-22.
  • Banerjee A, Pathak S, Jothimani G, Roy S. Antiproliferative effects of combinational therapy of Lycopodium clavatum and quercetin in colon cancer cells. J Basic Clin Physiol Pharmacol. 2020;31:1-12.
  • Samadder A, Das S, Das J, Paul A, Boujedaini N, Khuda-Bukhsh AR. The potentized homeopathic drug, lycopodium clavatum (5C and 15C) has anti-cancer effect on HeLa cells in vitro. J Acupunct Meridian Stud. 2013;6:180-7.
  • Mu S, Liu Z, Duan M, Yan Y, Liu G, Liu S et al. Transdermal permeation research of ethanol extracts from Lycopodium clavatum. IOP Conf Ser: Earth Environ Sci. 2020;559:012026.
  • Goswami HK, Sen K, Mukhopadhyay R. Pteridophytes: evolutionary boon as medicinal plants. Plant Genet Resour. 2016;14:328-55.
  • Bishayee K, Chakraborty D, Ghosh S, Boujedaini N, Khuda-Bukhsh AR. Lycopodine triggers apoptosis by modulating 5-lipoxygenase, and depolarizing mitochondrial membrane potential in androgen sensitive and refractory prostate cancer cells without modulating p53 activity: signaling cascade and drug-DNA interaction. Eur J Pharmacol. 2013;698:110-21.
  • Pongpamorn P, Wan-erlor S, Ruchirawat S, Thasana N. Semi-synthetic studies of α-onocerin derivatives for cytotoxicity. Phytochem Lett. 2018;23:106-15.
  • Jo A, Een Kim C, Lee M. Serratane triterpenoids isolated from Lycopodium clavatum by bioactivity-guided fractionation attenuate the production of inflammatory mediators. Bioorg Chem. 2020;96:103632.
  • Mundargi RC, Tan EL, Seo J, Cho NJ. Encapsulation and controlled release formulations of 5-fluorouracil from natural Lycopodium clavatum spores. J Ind Eng Chem. 2016;36:102-8.
  • Fulda S, Galluzzi L, Kroemer G. Targeting mitochondria for cancer therapy. Nat Rev Drug Disc. 2010;9:447-64.
  • Rai NK, Tripathi K, Sharma D, Shukla VK. Apoptosis: a basic physiologic process in wound healing. Int J Low Extrem Wounds. 2005;4:138-44.

Apoptotic effects of Lycopodium clavatum extract on SKBR-3 human breast cancer cells

Year 2023, Volume: 48 Issue: 4, 1207 - 1216, 29.12.2023
https://doi.org/10.17826/cumj.1336606

Abstract

Purpose: Breast cancer is an important public health problem worldwide. Natural compounds derived from plants have emerged as promising candidates for fighting cancer due to their safety, minimal toxicity, and potential effectiveness. This study investigated the apoptotic effect of the ethanol extract of Lycopodium clavatum on SKBR-3 human breast cancer cells.
Materials and Methods: The effect of applying Lycopodium clavatum ethanol extract at different doses (100, 200, and 300 µg/mL) and duration (12, 24, and 48 hours) to evaluate the viability of human breast cancer cells was investigated using the WST-1 cytotoxicity test. Also, the mechanism of apoptosis of Lycopodium clavatum ethanol extract was investigated by intrinsic (BAX and Caspase-9) and extrinsic (Caspase-8 and Caspase-3) pathways.
Results: The application of Lycopodium clavatum ethanol extract had a cytotoxic effect on SKBR-3 cells and this effect was dependent on the dose and duration of treatment. After 12 hours of incubation with LC-EE, 10%, 25%, and 40% cell death were observed in the 100, 200, and 300 µg/mL groups, respectively, compared to the control group. Additionally, our findings demonstrate that Lycopodium clavatum treatment induces the stimulation of apoptotic proteins, including BAX, Caspase-9, Caspase-8, and Caspase-3.
Conclusion: The anti-cancer effect of Lycopodium clavatum ethanol extract in SKBR-3 cells was determined by activating intrinsic and extrinsic apoptotic pathways. These findings suggest that Lycopodium clavatum may assist in the development of new therapeutic strategies as an effective anti-cancer agent against human breast cancer.

Supporting Institution

Scientific and Technological Research Council of Turkey (TUBITAK)

Project Number

1919B012217673

References

  • Azamjah N, Soltan-Zadeh Y, Zayeri F. Global trend of breast cancer mortality rate: a 25-year study. Asian Pac J Cancer Prev. 2019;20:2015-2020.
  • Naeem M, Iqbal MO, Khan H, Ahmed MM, Farooq M, Aadil MM, et al. A review of twenty years of research on the regulation of signaling pathways by natural products in breast cancer. Molecules. 2022;27:3412.
  • Das S, Das J, Samadder A, Boujedaini N, Khuda-Bukhsh AR. Apigenin-induced apoptosis in A375 and A549 cells through selective action and dysfunction of mitochondria. Exp Biol Med. 2012;237:1433-48.
  • Banerjee JN, Biswas S, Madhu NR, Karmakar SR, Biswas SJ. A better understanding of pharmacological activities and uses of phytochemicals of Lycopodium clavatum: A review. J Pharmacogn Phytochem. 2014;3:207-10.
  • Mandal SK, Biswas R, Bhattacharyya SS, Paul S, Dutta S, Pathak S, et al. Lycopodine from Lycopodium clavatum extract inhibits proliferation of HeLa cells through induction of apoptosis via caspase-3 activation. Eur J Pharmacol. 2010;626:115-22.
  • Banerjee A, Pathak S, Jothimani G, Roy S. Antiproliferative effects of combinational therapy of Lycopodium clavatum and quercetin in colon cancer cells. J Basic Clin Physiol Pharmacol. 2020;31:1-12.
  • Samadder A, Das S, Das J, Paul A, Boujedaini N, Khuda-Bukhsh AR. The potentized homeopathic drug, lycopodium clavatum (5C and 15C) has anti-cancer effect on HeLa cells in vitro. J Acupunct Meridian Stud. 2013;6:180-7.
  • Mu S, Liu Z, Duan M, Yan Y, Liu G, Liu S et al. Transdermal permeation research of ethanol extracts from Lycopodium clavatum. IOP Conf Ser: Earth Environ Sci. 2020;559:012026.
  • Goswami HK, Sen K, Mukhopadhyay R. Pteridophytes: evolutionary boon as medicinal plants. Plant Genet Resour. 2016;14:328-55.
  • Bishayee K, Chakraborty D, Ghosh S, Boujedaini N, Khuda-Bukhsh AR. Lycopodine triggers apoptosis by modulating 5-lipoxygenase, and depolarizing mitochondrial membrane potential in androgen sensitive and refractory prostate cancer cells without modulating p53 activity: signaling cascade and drug-DNA interaction. Eur J Pharmacol. 2013;698:110-21.
  • Pongpamorn P, Wan-erlor S, Ruchirawat S, Thasana N. Semi-synthetic studies of α-onocerin derivatives for cytotoxicity. Phytochem Lett. 2018;23:106-15.
  • Jo A, Een Kim C, Lee M. Serratane triterpenoids isolated from Lycopodium clavatum by bioactivity-guided fractionation attenuate the production of inflammatory mediators. Bioorg Chem. 2020;96:103632.
  • Mundargi RC, Tan EL, Seo J, Cho NJ. Encapsulation and controlled release formulations of 5-fluorouracil from natural Lycopodium clavatum spores. J Ind Eng Chem. 2016;36:102-8.
  • Fulda S, Galluzzi L, Kroemer G. Targeting mitochondria for cancer therapy. Nat Rev Drug Disc. 2010;9:447-64.
  • Rai NK, Tripathi K, Sharma D, Shukla VK. Apoptosis: a basic physiologic process in wound healing. Int J Low Extrem Wounds. 2005;4:138-44.
There are 15 citations in total.

Details

Primary Language English
Subjects Cancer Cell Biology, Cancer Therapy (Excl. Chemotherapy and Radiation Therapy)
Journal Section Research
Authors

Mohammad Reza Dastouri 0000-0003-3882-0728

Yusuf Küçükbağrıaçık 0000-0002-4909-2669

Project Number 1919B012217673
Publication Date December 29, 2023
Acceptance Date October 16, 2023
Published in Issue Year 2023 Volume: 48 Issue: 4

Cite

MLA Dastouri, Mohammad Reza and Yusuf Küçükbağrıaçık. “Apoptotic Effects of Lycopodium Clavatum Extract on SKBR-3 Human Breast Cancer Cells”. Cukurova Medical Journal, vol. 48, no. 4, 2023, pp. 1207-16, doi:10.17826/cumj.1336606.