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The effects of Hypericum crenulatum polysaccharides on the proliferation of cancer cells

Year 2020, Volume: 3 Issue: 1, 1 - 6, 21.04.2020
https://doi.org/10.33713/egetbd.647464

Abstract

The goal in the cancer treatment is
to induce tumor cell death without damaging healthy cells and to prevent the
spread of these cells to other organs.
In the case of metastasis, the cure protocols may be inadequate.
Alternative methods are used to support treatment. For this purpose, herbal
products are widely used. In our experiment, we aimed to investigate the effect
of Hypericum crenulatum
polysaccharides on the proliferation of breast cancer cell lines. Hypericum crenulatum polysaccharides
were isolated and were exposed to the MCF-7 and MDA-MB-231 cells  at different dilutions,  then IC50 doses for each cells
were calculated using MTT assay. Breast cancer cells were treated with IC50 doses of
polysaccharides for 24 hours and immunocytochemistry was performed to evaluate
the expressions of metastases and proliferation markers, PI3K, Akt-1 and
Erk-1/2. The staining results were evaluated by H-score and the difference
between the groups was analyzed statistically. Hypericum crenulatum polysaccharides were found to be toxic to both
breast cancer cells by MTT method. When PI3K, Akt-1 and Erk-1/2 markers of
proliferation and metastasis were evaluated, it was seen that there was a
significant decrease compared to the control group. Since MDA-MB-231 cells are
ER (-), their invasion ability is over compared to MCF-7 ER (+)  cells. For this reason, the toxic effect of
polysaccharides was found to be higher in MCF-7 cells. As a result, in vivo studies are needed to be performed
following the the antiproliferative effects of herbal products are found in vitro.

References

  • 1. Hasegawa T, Adachi R, Iwakata H, Takeno T, Sato K, Sakamaki T. ErbB2 signalingepigenetically suppresses microRNA-205 transcription via Ras/Raf/MEK/ERK pathway in breast cancer. FEBS Open Bio 2017; 7(8):1154-1165. doi:10.1002/2211-5463.12256.
  • 2. Gagliato DM, Jardim DL, Marchesi MS and Hortobagyi GN. Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2+ breast cancer. Oncotarget 2016; 7, 64431–64446.
  • 3. Liu S, Chen S, Yuan W, Wang H, Chen K, Li D, Li D. PD-1/PD-L1 interaction up-regulates MDR1/P-gp expression in breast cancer cells via PI3K/AKT and MAPK/ERK pathways. Oncotarget 2017; 8(59):99901-99912. doi:10.18632/oncotarget.21914.
  • 4. Han R, Gu S, Zhang Y, Luo A, Jing X, Zhao L, Zhao X, Zhang L. Estrogen promotes progression of hormone-dependent breast cancer through CCL2-CCR2 axis by upregulation of Twist via PI3K/AKT/NF-κB signaling. Sci Rep 2018; 8(1):9575. doi: 10.1038/s41598-018-27810-6.
  • 5. Weigelt B, Warne PH and Downward J. PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs. Oncogene 2011; 30, 3222–3233.
  • 6. Adamczyk A, Niemiec J, Janecka A, Harazin- Lechowska A, Ambicka A, Grela-Wojewoda A, Domagala-Haduch M, Cedrych I, Majchrzyk K, Kruczak A et al. Prognostic value of PIK3CA mutation status, PTEN and androgen receptor expression for metastasis-free survival in HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting. Pol J Pathol 2015; 66, 133–141.
  • 7. Qin H, Liu L, Sun S, Zhang D, Sheng J, Li B, Yang W. The impact of PI3K inhibitors on breast cancer cell and its tumor microenvironment. PeerJ 2018; 6:e5092. doi: 10.7717/peerj.5092.
  • 8. Franco P, Rampino M, Ostellino O, Schena M, Pecorari G, Garzino Demo P, Fasolis M, Arcadipane F, Martini S, Cavallin C, Airoldi M, Ricardi U. Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients. Med Oncol 2017; 34(2):30. doi: 10.1007/s12032-017-0886-5.
  • 9. Werthmann PG, Inter P, Welsch T, Sturm AK, Grützmann R, Debus M, Sterner MG, Kienle GS. Long-term tumor-free survival in a metastatic pancreatic carcinoma patient with FOLFIRINOX/Mitomycin, high-dose, fever inducing Viscum album extracts and subsequent R0 resection: A case report. Medicine (Baltimore) 2018; 97(49):e13243. doi: 10.1097/MD.0000000000013243.
  • 10. Costea T, Hudiță A, Ciolac OA, Gălățeanu B, Ginghină O, Costache M, Ganea C, Mocanu MM. Chemoprevention of Colorectal Cancer by Dietary Compounds. Int J Mol Sci 2018; 19(12). pii: E3787. doi: 10.3390/ijms19123787.
  • 11. Schempp CM, Kirkin V, Simon-Haarhaus B, Kersten A, Kiss J, Termeer CC, Gilb B, Kaufmann T, Borner C, Sleeman JP, Simon JC. Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis. Oncogene 2002; 21(8):1242-50.
  • 12. Ocak Z, Acar M, Gunduz E, Gunduz M, Demircan K, Uyeturk U, Ozlü T. Effect of hypericin on the ADAMTS-9 and ADAMTS-8 gene expression in MCF7 breast cancer cells. Eur Rev Med Pharmacol Sci 2013; 17(9):1185-90.
  • 13. Yi J, Yang X, Zheng L, Yang G, Sun L, Bao Y, Wu Y, Huang Y, Yu C, Yang SN, Li Y. Photoactivation of hypericin decreases the viability of RINm5F insulinoma cells through reduction in JNK/ERK phosphorylation and elevation of caspase-9/caspase-3 cleavage and Bax-to-Bcl-2 ratio. Biosci Rep 2015; 35(3). pii: e00195. doi: 10.1042/BSR20150028.
  • 14. You Lv , Xingbin Yang , Yan Zhao, Yun Ruan, Ying Yang, Zhezhi Wang. Separation and quantification of component monosaccharides of the tea polysaccharides from Gynostemma pentaphyllum by HPLC with indirect UV detection. Food Chemistry 2009; 742–746.
  • 15. Deliloglu-Gurhan I, Tuglu I, Vatansever HS, Ozdal-Kurt F, Ekren H, Taylan M, Sen BH. The effect of osteogenic medium on the adhesion of rat bone marrow stromal cell to the hydroxyapatite. Saudi Med J 2006; 27(3):305-11.
  • 16. Ozdal-Kurt F, Tuğlu I, Vatansever HS, Tong S, Şen BH, Deliloğlu-Gürhan SI. The effect of different implant biomaterials on the behavior of canine bone marrow stromal cells during their differentiation into osteoblasts. Biotech Histochem 2016; 91(6):412-22, 2016. doi: 10.1080/10520295.2016.1183819.
  • 17. Ozbilgin K, Karaca F, Turan A, Köse C, Vatansever S, Ozcakir T. 2015. The higher heparin-binding epidermal growth factor (HB-EGF) in missed abortion. Taiwan. J. Obstet. Gynecol 2015; 54 (1), 13e18.
  • 18. Mirmalek SA, Azizi MA, Jangholi E, Yadollah-Damavandi S, Javidi MA, Parsa Y, Parsa T, Salimi-Tabatabaee SA, Ghasemzadeh Kolagar H, Alizadeh-Navaei R. Cytotoxic and apoptogenic effect of hypericin, the bioactive component of Hypericum perforatum on the MCF-7 human breast cancer cell line. Cancer Cell Int 2016; 16:3. doi: 10.1186/s12935 016-0279-4.
  • 19. Kleemann B, Loos B, Scriba TJ, Lang D, Davids LM. St John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell death. PLoS One 2014; 9(7):e103762. doi: 10.1371/journal.pone.0103762.
  • 20. Hamzeloo-Moghadam M, Khalaj A, Malekmohammadi M. Cytotoxic Activity and Apoptosis Induction of Hypericum scabrum L. Iran Red Crescent Med J 2015; 17(10):e19453. doi: 10.5812/ircmj.19453.
  • 21. Fu T, Wang L, Jin XN, Sui HJ, Liu Z, Jin Y. Hyperoside induces both autophagy and apoptosis in non-small cell lung cancer cells in vitro. Acta Pharmacol Sin 2016; 37(4):505-18. doi: 10.1038/aps.2015.148.
  • 22. Bender O, Llorent-Martínez EJ, Zengin G, Mollica A, Ceylan R, Molina-García L, Fernández-de Córdova ML, Atalay A. Integration of in vitro and in silico perspectives to explain chemical characterization, biological potential and anticancer effects of Hypericum salsugineum: A pharmacologically active source for functional drug formulations. PLoS One 2018; 13(6):e0197815. doi: 10.1371/journal.pone.0197815.
  • 23. Borawska MH, Naliwajko SK, Moskwa J, Markiewicz-Żukowska R, Puścion-Jakubik A,Soroczyńska J. Anti-proliferative and anti-migration effects of Polish propolis combined with Hypericum perforatum L. on glioblastoma multiforme cell line U87MG. BMC Complement Altern Med 2016; 16:367. doi: 10.1186/s12906-016-1351-2.
  • 24. Sun B, Wang G, Liu H, Liu P, Twal WO, Cheung H, Carroll SL, Ethier SP, Mevers EE, Clardy J, Roberts T, Chen C, Li Q, Wang L, Yang M, Zhao JJ, Wang Q. Oridonin inhibits aberrant AKT activation in breast cancer. Oncotarget 2018; 9(35):23878-23889. doi: 10.18632/oncotarget.24378.
  • 25. Sun X, Ma X, Li Q, Yang Y, Xu X, Sun J, Yu M, Cao K, Yang L, Yang G, Zhang G, Wang X. Anti cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies. Int J Mol Med 2018; 42(2):811-820. doi: 10.3892/ijmm.2018.3654.
Year 2020, Volume: 3 Issue: 1, 1 - 6, 21.04.2020
https://doi.org/10.33713/egetbd.647464

Abstract

References

  • 1. Hasegawa T, Adachi R, Iwakata H, Takeno T, Sato K, Sakamaki T. ErbB2 signalingepigenetically suppresses microRNA-205 transcription via Ras/Raf/MEK/ERK pathway in breast cancer. FEBS Open Bio 2017; 7(8):1154-1165. doi:10.1002/2211-5463.12256.
  • 2. Gagliato DM, Jardim DL, Marchesi MS and Hortobagyi GN. Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2+ breast cancer. Oncotarget 2016; 7, 64431–64446.
  • 3. Liu S, Chen S, Yuan W, Wang H, Chen K, Li D, Li D. PD-1/PD-L1 interaction up-regulates MDR1/P-gp expression in breast cancer cells via PI3K/AKT and MAPK/ERK pathways. Oncotarget 2017; 8(59):99901-99912. doi:10.18632/oncotarget.21914.
  • 4. Han R, Gu S, Zhang Y, Luo A, Jing X, Zhao L, Zhao X, Zhang L. Estrogen promotes progression of hormone-dependent breast cancer through CCL2-CCR2 axis by upregulation of Twist via PI3K/AKT/NF-κB signaling. Sci Rep 2018; 8(1):9575. doi: 10.1038/s41598-018-27810-6.
  • 5. Weigelt B, Warne PH and Downward J. PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs. Oncogene 2011; 30, 3222–3233.
  • 6. Adamczyk A, Niemiec J, Janecka A, Harazin- Lechowska A, Ambicka A, Grela-Wojewoda A, Domagala-Haduch M, Cedrych I, Majchrzyk K, Kruczak A et al. Prognostic value of PIK3CA mutation status, PTEN and androgen receptor expression for metastasis-free survival in HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting. Pol J Pathol 2015; 66, 133–141.
  • 7. Qin H, Liu L, Sun S, Zhang D, Sheng J, Li B, Yang W. The impact of PI3K inhibitors on breast cancer cell and its tumor microenvironment. PeerJ 2018; 6:e5092. doi: 10.7717/peerj.5092.
  • 8. Franco P, Rampino M, Ostellino O, Schena M, Pecorari G, Garzino Demo P, Fasolis M, Arcadipane F, Martini S, Cavallin C, Airoldi M, Ricardi U. Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients. Med Oncol 2017; 34(2):30. doi: 10.1007/s12032-017-0886-5.
  • 9. Werthmann PG, Inter P, Welsch T, Sturm AK, Grützmann R, Debus M, Sterner MG, Kienle GS. Long-term tumor-free survival in a metastatic pancreatic carcinoma patient with FOLFIRINOX/Mitomycin, high-dose, fever inducing Viscum album extracts and subsequent R0 resection: A case report. Medicine (Baltimore) 2018; 97(49):e13243. doi: 10.1097/MD.0000000000013243.
  • 10. Costea T, Hudiță A, Ciolac OA, Gălățeanu B, Ginghină O, Costache M, Ganea C, Mocanu MM. Chemoprevention of Colorectal Cancer by Dietary Compounds. Int J Mol Sci 2018; 19(12). pii: E3787. doi: 10.3390/ijms19123787.
  • 11. Schempp CM, Kirkin V, Simon-Haarhaus B, Kersten A, Kiss J, Termeer CC, Gilb B, Kaufmann T, Borner C, Sleeman JP, Simon JC. Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis. Oncogene 2002; 21(8):1242-50.
  • 12. Ocak Z, Acar M, Gunduz E, Gunduz M, Demircan K, Uyeturk U, Ozlü T. Effect of hypericin on the ADAMTS-9 and ADAMTS-8 gene expression in MCF7 breast cancer cells. Eur Rev Med Pharmacol Sci 2013; 17(9):1185-90.
  • 13. Yi J, Yang X, Zheng L, Yang G, Sun L, Bao Y, Wu Y, Huang Y, Yu C, Yang SN, Li Y. Photoactivation of hypericin decreases the viability of RINm5F insulinoma cells through reduction in JNK/ERK phosphorylation and elevation of caspase-9/caspase-3 cleavage and Bax-to-Bcl-2 ratio. Biosci Rep 2015; 35(3). pii: e00195. doi: 10.1042/BSR20150028.
  • 14. You Lv , Xingbin Yang , Yan Zhao, Yun Ruan, Ying Yang, Zhezhi Wang. Separation and quantification of component monosaccharides of the tea polysaccharides from Gynostemma pentaphyllum by HPLC with indirect UV detection. Food Chemistry 2009; 742–746.
  • 15. Deliloglu-Gurhan I, Tuglu I, Vatansever HS, Ozdal-Kurt F, Ekren H, Taylan M, Sen BH. The effect of osteogenic medium on the adhesion of rat bone marrow stromal cell to the hydroxyapatite. Saudi Med J 2006; 27(3):305-11.
  • 16. Ozdal-Kurt F, Tuğlu I, Vatansever HS, Tong S, Şen BH, Deliloğlu-Gürhan SI. The effect of different implant biomaterials on the behavior of canine bone marrow stromal cells during their differentiation into osteoblasts. Biotech Histochem 2016; 91(6):412-22, 2016. doi: 10.1080/10520295.2016.1183819.
  • 17. Ozbilgin K, Karaca F, Turan A, Köse C, Vatansever S, Ozcakir T. 2015. The higher heparin-binding epidermal growth factor (HB-EGF) in missed abortion. Taiwan. J. Obstet. Gynecol 2015; 54 (1), 13e18.
  • 18. Mirmalek SA, Azizi MA, Jangholi E, Yadollah-Damavandi S, Javidi MA, Parsa Y, Parsa T, Salimi-Tabatabaee SA, Ghasemzadeh Kolagar H, Alizadeh-Navaei R. Cytotoxic and apoptogenic effect of hypericin, the bioactive component of Hypericum perforatum on the MCF-7 human breast cancer cell line. Cancer Cell Int 2016; 16:3. doi: 10.1186/s12935 016-0279-4.
  • 19. Kleemann B, Loos B, Scriba TJ, Lang D, Davids LM. St John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell death. PLoS One 2014; 9(7):e103762. doi: 10.1371/journal.pone.0103762.
  • 20. Hamzeloo-Moghadam M, Khalaj A, Malekmohammadi M. Cytotoxic Activity and Apoptosis Induction of Hypericum scabrum L. Iran Red Crescent Med J 2015; 17(10):e19453. doi: 10.5812/ircmj.19453.
  • 21. Fu T, Wang L, Jin XN, Sui HJ, Liu Z, Jin Y. Hyperoside induces both autophagy and apoptosis in non-small cell lung cancer cells in vitro. Acta Pharmacol Sin 2016; 37(4):505-18. doi: 10.1038/aps.2015.148.
  • 22. Bender O, Llorent-Martínez EJ, Zengin G, Mollica A, Ceylan R, Molina-García L, Fernández-de Córdova ML, Atalay A. Integration of in vitro and in silico perspectives to explain chemical characterization, biological potential and anticancer effects of Hypericum salsugineum: A pharmacologically active source for functional drug formulations. PLoS One 2018; 13(6):e0197815. doi: 10.1371/journal.pone.0197815.
  • 23. Borawska MH, Naliwajko SK, Moskwa J, Markiewicz-Żukowska R, Puścion-Jakubik A,Soroczyńska J. Anti-proliferative and anti-migration effects of Polish propolis combined with Hypericum perforatum L. on glioblastoma multiforme cell line U87MG. BMC Complement Altern Med 2016; 16:367. doi: 10.1186/s12906-016-1351-2.
  • 24. Sun B, Wang G, Liu H, Liu P, Twal WO, Cheung H, Carroll SL, Ethier SP, Mevers EE, Clardy J, Roberts T, Chen C, Li Q, Wang L, Yang M, Zhao JJ, Wang Q. Oridonin inhibits aberrant AKT activation in breast cancer. Oncotarget 2018; 9(35):23878-23889. doi: 10.18632/oncotarget.24378.
  • 25. Sun X, Ma X, Li Q, Yang Y, Xu X, Sun J, Yu M, Cao K, Yang L, Yang G, Zhang G, Wang X. Anti cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies. Int J Mol Med 2018; 42(2):811-820. doi: 10.3892/ijmm.2018.3654.
There are 25 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Original Investigation
Authors

İşil Aydemir 0000-0002-4143-7319

Oktay Ozkan This is me 0000-0002-9794-8863

Ahmet Savran This is me 0000-0003-4609-9547

Publication Date April 21, 2020
Acceptance Date December 25, 2019
Published in Issue Year 2020 Volume: 3 Issue: 1

Cite

EndNote Aydemir İ, Ozkan O, Savran A (April 1, 2020) The effects of Hypericum crenulatum polysaccharides on the proliferation of cancer cells. Ege Tıp Bilimleri Dergisi 3 1 1–6.

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