Molecular Targets of Plant-based Alkaloids and Polyphenolics in Liver and Breast Cancer- An Insight into Anticancer Drug Development

  • Authors: Batool S.1, Asim L.2, Qureshi F.3, Masood A.4, Mushtaq M.5, Saleem R.6
  • Affiliations:
    1. Department of Basic and Applied Chemistry, Faculty of Science and Technology University of Central Punjab,
    2. Department of Basic and Applied Chemistry,, Faculty of Science and Technology University of Central Punjab
    3. Department of Basic and Applied Chemistry,, Faculty of Science and Technology University of Central Punjab,
    4. Department of Biotechnology,, Faculty of Science and Technology University of Central Punjab,
    5. Department of Technical Laboratory Analytics,, Abu Dhabi Vocational Education and Training Institute (ADVETI)
    6. Department of Chemistry and Chemical Engineering, SBA School of Science and Engineering (SBASSE),, Lahore University of Management Sciences (LUMS)
  • Issue: Vol 25, No 5 (2025)
  • Pages: 295-312
  • Section: Oncology
  • URL: https://filvestnik.nvsu.ru/1871-5206/article/view/694492
  • DOI: https://doi.org/10.2174/0118715206302216240628072554
  • ID: 694492

Cite item

Full Text

Abstract

Liver and Breast cancer are ranked as the most prevailing cancers that cause high cancer-related mortality. As cancer is a life-threatening disease that affects the human population globally, there is a need to develop novel therapies. Among the available treatment options include radiotherapy, chemotherapy, surgery, and immunotherapy. The most superlative modern method is the use of plant-derived anticancer drugs that target the cancerous cells and inhibit their proliferation. Plant-derived compounds are generally considered safer than synthetic drugs/traditional therapies and could serve as potential novel targets to treat liver and breast cancer to revolutionize cancer treatment. Alkaloids and Polyphenols have been shown to act as anticancer agents through molecular approaches. They disrupt various cellular mechanisms, inhibit the production of cyclins and CDKs to arrest the cell cycle, and activate the DNA repairing mechanism by upregulating p53, p21, and p38 expression. In severe cases, when no repair is possible, they induce apoptosis in liver and breast cancer cells by activating caspase-3, 8, and 9 and increasing the Bax/Bcl-2 ratio. They also deactivate several signaling pathways, such as PI3K/AKT/mTOR, STAT3, NF-κB, Shh, MAPK/ERK, and Wnt/β-catenin pathways, to control cancer cell progression and metastasis. The highlights of this review are the regulation of specific protein expressions that are crucial in cancer, such as in HER2 over-expressing breast cancer cells; alkaloids and polyphenols have been reported to reduce HER2 as well as MMP expression. This study reviewed more than 40 of the plant-based alkaloids and polyphenols with specific molecular targets against liver and breast cancer. Among them, Oxymatrine, Hirsutine, Piperine, Solamargine, and Brucine are currently under clinical trials by qualifying as potent anticancer agents due to lesser side effects. As a lot of research is there on anticancer compounds, there is a desideratum to compile data to move towards clinical trials phase 4 and control the prevalence of liver and breast cancer.

About the authors

Salma Batool

Department of Basic and Applied Chemistry, Faculty of Science and Technology University of Central Punjab,

Author for correspondence.
Email: info@benthamscience.net

Laiba Asim

Department of Basic and Applied Chemistry,, Faculty of Science and Technology University of Central Punjab

Email: info@benthamscience.net

Fawad Qureshi

Department of Basic and Applied Chemistry,, Faculty of Science and Technology University of Central Punjab,

Email: info@benthamscience.net

Ammara Masood

Department of Biotechnology,, Faculty of Science and Technology University of Central Punjab,

Email: info@benthamscience.net

Maria Mushtaq

Department of Technical Laboratory Analytics,, Abu Dhabi Vocational Education and Training Institute (ADVETI)

Email: info@benthamscience.net

Rahman Saleem

Department of Chemistry and Chemical Engineering, SBA School of Science and Engineering (SBASSE),, Lahore University of Management Sciences (LUMS)

Email: info@benthamscience.net

References

  1. Yu, X.N.; Chen, H.; Liu, T.T.; Wu, J.; Zhu, J.M.; Shen, X.Z. Targeting the mTOR regulatory network in hepatocellular carcinoma: Are we making headway? Biochim. Biophys. Acta Rev. Cancer, 2019, 1871(2), 379-391. doi: 10.1016/j.bbcan.2019.03.001 PMID: 30951815
  2. Jeong, S.; Zheng, B.; Wang, H.; Xia, Q.; Chen, L. Nervous system and primary liver cancer. Biochim. Biophys. Acta Rev. Cancer, 2018, 1869(2), 286-292. doi: 10.1016/j.bbcan.2018.04.002 PMID: 29660379
  3. Liu, W; Zhang, Q; Tang, Q; Hu, C; Huang, J; Liu, Y Lycorine inhibits cell proliferation and migration by inhibiting ROCK1/cofilin-induced actin dynamics in HepG2 hepatoblastoma cells. Oncol Rep., 2018, 40(4), 2298-2306.
  4. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424. doi: 10.3322/caac.21492 PMID: 30207593
  5. DeSantis, C.E.; Ma, J.; Gaudet, M.M.; Newman, L.A.; Miller, K.D.; Goding Sauer, A.; Jemal, A.; Siegel, R.L. Breast cancer statistics, 2019. CA Cancer J. Clin., 2019, 69(6), 438-451. doi: 10.3322/caac.21583 PMID: 31577379
  6. Nagalingam, A.; Arbiser, J.L.; Bonner, M.Y.; Saxena, N.K.; Sharma, D. Honokiol activates AMP-activated protein kinase in breast cancer cells via an LKB1-dependent pathway and inhibits breast carcinogenesis. Breast Cancer Res., 2012, 14(1), R35. doi: 10.1186/bcr3128 PMID: 22353783
  7. Bale, R.; Putzer, D.; Schullian, P. Local treatment of breast cancer liver metastasis. Cancers, 2019, 11(9), 1341. doi: 10.3390/cancers11091341 PMID: 31514362
  8. Semenza, G.L. Cancer–stromal cell interactions mediated by hypoxia-inducible factors promote angiogenesis, lymphangiogenesis, and metastasis. Oncogene, 2013, 32(35), 4057-4063. doi: 10.1038/onc.2012.578 PMID: 23222717
  9. Ma, R.; Feng, Y.; Lin, S.; Chen, J.; Lin, H.; Liang, X.; Zheng, H.; Cai, X. Mechanisms involved in breast cancer liver metastasis. J. Transl. Med., 2015, 13(1), 64. doi: 10.1186/s12967-015-0425-0 PMID: 25885919
  10. Keating, G.M. Sorafenib: A review in hepatocellular carcinoma. Target. Oncol., 2017, 12(2), 243-253. doi: 10.1007/s11523-017-0484-7 PMID: 28299600
  11. Tinkle, CL; Haas-Kogan, D Hepatocellular carcinoma: Natural history, current management, and emerging tools. J. Biologics: Targets Ther., 2012, 6, 207.
  12. Furrukh, M.; Qureshi, A. Treatment of breast cancer; Review and updates. J. Ayub Med. Coll. Abbottabad, 2018, 30(2), 264-274. PMID: 29938432
  13. Lamb, C.A.; Vanzulli, S.I.; Lanari, C. Hormone receptors in breast cancer: More than estrogen receptors. Medicina, 2019, 79(Spec 6/1), 540-545. PMID: 31864223
  14. You, L.; An, R.; Liang, K.; Wang, X. Anti-breast cancer agents from Chinese herbal medicines. Mini Rev. Med. Chem., 2013, 13(1), 101-105. doi: 10.2174/138955713804484785 PMID: 23020239
  15. Kabera, J.N.; Semana, E.; Mussa, A.R.; He, X. Plant secondary metabolites: Biosynthesis, classification, function and pharmacological properties. J. Pharm. Pharmacol., 2014, 2(7), 377-392.
  16. Tiwari, R.; Rana, C. Plant secondary metabolites: A review. Int. J. Eng. Res. Gen. Sci., 2015, 3(5), 661-670.
  17. Anttila, J.V.; Shubin, M.; Cairns, J.; Borse, F.; Guo, Q.; Mononen, T.; Vázquez-García, I.; Pulkkinen, O.; Mustonen, V. Contrasting the impact of cytotoxic and cytostatic drug therapies on tumour progression. PLOS Comput. Biol., 2019, 15(11), e1007493. doi: 10.1371/journal.pcbi.1007493 PMID: 31738747
  18. Kulchitsky, A.; Potkin, I.; Zubenko, S.; Chernov, N.; Talabaev, V.; Demidchik, E. Cytotoxic effects of chemotherapeutic drugs and heterocyclic compounds at application on the cells of primary culture of neuroepithelium tumors. J. Med. Chem., 2012, 8(1), 22-32.
  19. Khalid, E.B.; Ayman, E.L.M.E.L.K.; Rahman, H.; Abdelkarim, G.; Najda, A. Natural products against cancer angiogenesis. Tumour Biol., 2016, 37(11), 14513-14536. doi: 10.1007/s13277-016-5364-8 PMID: 27651162
  20. Wu, Q.; Yang, Z.; Nie, Y.; Shi, Y.; Fan, D. Multi-drug resistance in cancer chemotherapeutics: Mechanisms and lab approaches. Cancer Lett., 2014, 347(2), 159-166. doi: 10.1016/j.canlet.2014.03.013 PMID: 24657660
  21. Iqbal, J.; Abbasi, B.A.; Mahmood, T.; Kanwal, S.; Ali, B.; Shah, S.A.; Khalil, A.T. Plant-derived anticancer agents: A green anticancer approach. Asian Pac. J. Trop. Biomed., 2017, 7(12), 1129-1150. doi: 10.1016/j.apjtb.2017.10.016
  22. Foster, D.A.; Yellen, P.; Xu, L.; Saqcena, M. Regulation of G1 cell cycle progression: Distinguishing the restriction point from a nutrient-sensing cell growth checkpoint (s). Genes Cancer, 2010, 1(11), 1124-1131. doi: 10.1177/1947601910392989 PMID: 21779436
  23. Visconti, R.; Della, M.R.; Grieco, D. Cell cycle checkpoint in cancer: A therapeutically targetable double-edged sword. J. Exp. Clin. Cancer Res., 2016, 35(1), 153. doi: 10.1186/s13046-016-0433-9 PMID: 27670139
  24. Habli, Z.; Toumieh, G.; Fatfat, M.; Rahal, O.; Gali-Muhtasib, H. Emerging cytotoxic alkaloids in the battle against cancer: Overview of molecular mechanisms. Molecules, 2017, 22(2), 250. doi: 10.3390/molecules22020250 PMID: 28208712
  25. Pei, H.; Xue, L.; Tang, M.; Tang, H.; Kuang, S.; Wang, L.; Ma, X.; Cai, X.; Li, Y.; Zhao, M.; Peng, A.; Ye, H.; Chen, L. Alkaloids from black pepper (Piper nigrum L.) exhibit anti-inflammatory activity in murine macrophages by inhibiting activation of NF-κB pathway. J. Agric. Food Chem., 2020, 68(8), 2406-2417. doi: 10.1021/acs.jafc.9b07754 PMID: 32031370
  26. Ghosh, N.; Chaki, R.; Mandal, V.; Mandal, S.C. COX-2 as a target for cancer chemotherapy. Pharmacol. Rep., 2010, 62(2), 233-244. doi: 10.1016/S1734-1140(10)70262-0 PMID: 20508278
  27. Abdal Dayem, A.; Choi, H.; Yang, G.M.; Kim, K.; Saha, S.; Cho, S.G. The anti-cancer effect of polyphenols against breast cancer and cancer stem cells: Molecular mechanisms. Nutrients, 2016, 8(9), 581. doi: 10.3390/nu8090581 PMID: 27657126
  28. Singla, R.; Jaitak, V. Multitargeted molecular docking study of natural-derived alkaloids on breast cancer pathway components. Curr. Computeraided Drug Des., 2017, 13(4), 294-302. PMID: 28382865
  29. Cao, J.; Wei, R.; Yao, S. Matrine has pro-apoptotic effects on liver cancer by triggering mitochondrial fission and activating Mst1-JNK signalling pathways. J. Physiol. Sci., 2019, 69(2), 185-198. doi: 10.1007/s12576-018-0634-4 PMID: 30155612
  30. Qian, L.; Liu, Y.; Xu, Y.; Ji, W.; Wu, Q.; Liu, Y.; Gao, Q.; Su, C. Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Cancer Lett., 2015, 368(1), 126-134. doi: 10.1016/j.canlet.2015.07.035 PMID: 26259512
  31. Liu, C.; Yang, S.; Wang, K.; Bao, X.; Liu, Y.; Zhou, S.; Liu, H.; Qiu, Y.; Wang, T.; Yu, H. Alkaloids from traditional chinese medicine against hepatocellular carcinoma. Biomed. Pharmacother., 2019, 120, 109543. doi: 10.1016/j.biopha.2019.109543 PMID: 31655311
  32. Roy, M.; Liang, L.; Xiao, X.; Feng, P.; Ye, M.; Liu, J. Lycorine: A prospective natural lead for anticancer drug discovery. Biomed. Pharmacother., 2018, 107, 615-624. doi: 10.1016/j.biopha.2018.07.147 PMID: 30114645
  33. Li, F.; Dong, X.; Lin, P.; Jiang, J. Regulation of Akt/FoxO3a/Skp2 axis is critically involved in berberine-induced cell cycle arrest in hepatocellular carcinoma cells. Int. J. Mol. Sci., 2018, 19(2), 327. doi: 10.3390/ijms19020327 PMID: 29360760
  34. Jabbarzadeh Kaboli, P.; Rahmat, A.; Ismail, P.; Ling, K.H. Targets and mechanisms of berberine, a natural drug with potential to treat cancer with special focus on breast cancer. Eur. J. Pharmacol., 2014, 740, 584-595. doi: 10.1016/j.ejphar.2014.06.025 PMID: 24973693
  35. Sun, Y.; Wang, W.; Tong, Y. Berberine inhibits proliferative ability of breast cancer cells by reducing metadherin. Med. Sci. Monit., 2019, 25, 9058-9066. doi: 10.12659/MSM.914486 PMID: 31779025
  36. Guo, Y; Pei, X. Tetrandrine-induced autophagy in MDA-MB-231 triple-negative breast cancer cell through the inhibition of PI3K/AKT/mTOR signaling. Altern. Med. Rev., 2019, 2019, 7517431.
  37. Kang, Y.H.; Park, M.Y.; Yoon, D.Y.; Han, S.R.; Lee, C.I.; Ji, N.Y.; Myung, P.K.; Lee, H.G.; Kim, J.W.; Yeom, Y.I.; Jang, Y.J.; Ahn, D.K.; Kim, J.W.; Song, E.Y. Dysregulation of overexpressed IL-32α in hepatocellular carcinoma suppresses cell growth and induces apoptosis through inactivation of NF-κB and Bcl-2. Cancer Lett., 2012, 318(2), 226-233. doi: 10.1016/j.canlet.2011.12.023 PMID: 22198481
  38. Zhou, X.; Xu, Z.; Li, A.; Zhang, Z. Double-sides sticking mechanism of vinblastine interacting with α,β-tubulin to get activity against cancer cells. J. Biomol. Struct. Dyn., 2019, 37(15), 4080-4091.
  39. Lee, H.; Baek, S.; Lee, J.; Kim, C.; Ko, J.H.; Lee, S.G.; Chinnathambi, A.; Alharbi, S.; Yang, W.; Um, J.Y.; Sethi, G.; Ahn, K. Isorhynchophylline, a potent plant alkaloid, induces apoptotic and anti-metastatic effects in human hepatocellular carcinoma cells through the modulation of diverse cell signaling cascades. Int. J. Mol. Sci., 2017, 18(5), 1095. doi: 10.3390/ijms18051095 PMID: 28534824
  40. Shu, G.; Mi, X.; Cai, J.; Zhang, X.; Yin, W.; Yang, X.; Li, Y.; Chen, L.; Deng, X. Brucine, an alkaloid from seeds of Strychnos nux-vomica Linn., represses hepatocellular carcinoma cell migration and metastasis: The role of hypoxia inducible factor 1 pathway. Toxicol. Lett., 2013, 222(2), 91-101. doi: 10.1016/j.toxlet.2013.07.024 PMID: 23933019
  41. Saraswati, S.; Alhaider, A.A.; Agrawal, S.S. Anticarcinogenic effect of brucine in diethylnitrosamine initiated and phenobarbital-promoted hepatocarcinogenesis in rats. Chem. Biol. Interact., 2013, 206(2), 214-221. doi: 10.1016/j.cbi.2013.09.012 PMID: 24060683
  42. Deng, X.; Yin, F.; Lu, X.; Cai, B.; Yin, W. The apoptotic effect of brucine from the seed of Strychnos nux-vomica on human hepatoma cells is mediated via Bcl-2 and Ca2+ involved mitochondrial pathway. Toxicol. Sci., 2006, 91(1), 59-69. doi: 10.1093/toxsci/kfj114 PMID: 16443926
  43. Sani, I.K.; Marashi, S.H.; Kalalinia, F. Solamargine inhibits migration and invasion of human hepatocellular carcinoma cells through down-regulation of matrix metalloproteinases 2 and 9 expression and activity. Toxicol. In Vitro, 2015, 29(5), 893-900. doi: 10.1016/j.tiv.2015.03.012 PMID: 25819016
  44. Kalalinia, F.; Karimi-Sani, I. Anticancer properties of solamargine: A systematic review. Phytother. Res., 2017, 31(6), 858-870. doi: 10.1002/ptr.5809 PMID: 28383149
  45. Munari, C.C.; de Oliveira, P.F.; Campos, J.C.L.; Martins, S.P.L.; Da Costa, J.C.; Bastos, J.K.; Tavares, D.C. Antiproliferative activity of Solanum lycocarpum alkaloidic extract and their constituents, solamargine and solasonine, in tumor cell lines. J. Nat. Med., 2014, 68(1), 236-241. doi: 10.1007/s11418-013-0757-0 PMID: 23475509
  46. Zhou, L.; Li, X.; Chen, X.; Li, Z.; Liu, X.; Zhou, S.; Zhong, Q.; Yi, T.; Wei, Y.; Zhao, X.; Qian, Z. In vivo antitumor and antimetastatic activities of camptothecin encapsulated with N-trimethyl chitosan in a preclinical mouse model of liver cancer. Cancer Lett., 2010, 297(1), 56-64. doi: 10.1016/j.canlet.2010.04.024 PMID: 20546992
  47. Lin, B.; Li, D.; Zhang, L. Oxymatrine mediates Bax and Bcl-2 expression in human breast cancer MCF-7 cells. Pharmazie, 2016, 71(3), 154-157. PMID: 27183711
  48. Greenshields, A.L.; Doucette, C.D.; Sutton, K.M.; Madera, L.; Annan, H.; Yaffe, P.B.; Knickle, A.F.; Dong, Z.; Hoskin, D.W. Piperine inhibits the growth and motility of triple-negative breast cancer cells. Cancer Lett., 2015, 357(1), 129-140. doi: 10.1016/j.canlet.2014.11.017 PMID: 25444919
  49. Do, M.T.; Kim, H.G.; Choi, J.H.; Khanal, T.; Park, B.H.; Tran, T.P.; Jeong, T.C.; Jeong, H.G. Antitumor efficacy of piperine in the treatment of human HER2-overexpressing breast cancer cells. Food Chem., 2013, 141(3), 2591-2599. doi: 10.1016/j.foodchem.2013.04.125 PMID: 23870999
  50. Patel, S.; Sarwat, M.; Khan, T.H. Mechanism behind the anti-tumour potential of saffron ( Crocus sativus L.): The molecular perspective. Crit. Rev. Oncol. Hematol., 2017, 115, 27-35. doi: 10.1016/j.critrevonc.2017.04.010 PMID: 28602167
  51. Kim, BH; Park, J-W Epidemiology of liver cancer in South Korea. J. Clin. Mol. Hepatol., 2018, 24(1), 1. doi: 10.3350/cmh.2017.0112
  52. Yang, F.; Shi, L.; Liang, T.; Ji, L.; Zhang, G.; Shen, Y.; Zhu, F.; Xu, L. Anti-tumor effect of evodiamine by inducing Akt-mediated apoptosis in hepatocellular carcinoma. Biochem. Biophys. Res. Commun., 2017, 485(1), 54-61. doi: 10.1016/j.bbrc.2017.02.017 PMID: 28189683
  53. Lou, C.; Takahashi, K.; Irimura, T.; Saiki, I.; Hayakawa, Y. Identification of Hirsutine as an anti-metastatic phytochemical by targeting NF-κB activation. Int. J. Oncol., 2014, 45(5), 2085-2091. doi: 10.3892/ijo.2014.2624 PMID: 25175557
  54. Lou, C.; Yokoyama, S.; Saiki, I.; Hayakawa, Y. Selective anticancer activity of hirsutine against HER2-positive breast cancer cells by inducing DNA damage. Oncol. Rep., 2015, 33(4), 2072-2076. doi: 10.3892/or.2015.3796 PMID: 25672479
  55. Che, J.; Zhang, F.Z.; Zhao, C.Q.; Hu, X.D.; Fan, S.J. Cyclopamine is a novel Hedgehog signaling inhibitor with significant anti-proliferative, anti-invasive and anti-estrogenic potency in human breast cancer cells. Oncol. Lett., 2013, 5(4), 1417-1421. doi: 10.3892/ol.2013.1195 PMID: 23599805
  56. Isah, T. Anticancer alkaloids from trees: Development into drugs. Pharmacogn. Rev., 2016, 10(20), 90-99. doi: 10.4103/0973-7847.194047 PMID: 28082790
  57. Xie, S.; Zhou, J. Harnessing plant biodiversity for the discovery of novel anticancer drugs targeting microtubules. Front. Plant Sci., 2017, 8, 720. doi: 10.3389/fpls.2017.00720 PMID: 28523014
  58. Zhou, Y.; Zheng, J.; Li, Y.; Xu, D.P.; Li, S.; Chen, Y.M.; Li, H.B. Natural polyphenols for prevention and treatment of cancer. Nutrients, 2016, 8(8), 515. doi: 10.3390/nu8080515 PMID: 27556486
  59. Segun, P.A.; Ismail, F.M.D.; Ogbole, O.O.; Nahar, L.; Evans, A.R.; Ajaiyeoba, E.O.; Sarker, S.D. Acridone alkaloids from the stem bark of Citrus aurantium display selective cytotoxicity against breast, liver, lung and prostate human carcinoma cells. J. Ethnopharmacol., 2018, 227, 131-138. doi: 10.1016/j.jep.2018.08.039 PMID: 30189240
  60. Habartova, K.; Cahlíková, L.; Řezáčová, M.; Havelek, R. The biological activity of alkaloids from the Amaryllidaceae: From cholinesterases inhibition to anticancer activity Nat. Prod. Commun., 2016, 11(10), 1934578X1601101038. doi: 10.1177/1934578X1601101038
  61. Shiu, L.Y.; Liang, C.H.; Chang, L.C.; Sheu, H.M.; Tsai, E.M.; Kuo, K.W. Solamargine induces apoptosis and enhances susceptibility to trastuzumab and epirubicin in breast cancer cells with low or high expression levels of HER2/neu. Biosci. Rep., 2009, 29(1), 35-45. doi: 10.1042/BSR20080028 PMID: 18699774
  62. Zhang, X.; Harrington, N.; Moraes, R.C.; Wu, M.F.; Hilsenbeck, S.G.; Lewis, M.T. Cyclopamine inhibition of human breast cancer cell growth independent of Smoothened (Smo). Breast Cancer Res. Treat., 2009, 115(3), 505-521. doi: 10.1007/s10549-008-0093-3 PMID: 18563554
  63. Li, Y.; Guo, M.; Lin, Z.; Zhao, M.; Xiao, M.; Wang, C.; Xu, T.; Chen, T.; Zhu, B. Polyethylenimine-functionalized silver nanoparticle-based co-delivery of paclitaxel to induce HepG2 cell apoptosis. Int. J. Nanomedicine, 2016, 11, 6693-6702. doi: 10.2147/IJN.S122666 PMID: 27994465
  64. Avtanski, D.; Poretsky, L. Phyto-polyphenols as potential inhibitors of breast cancer metastasis. Mol. Med., 2018, 24(1), 29. doi: 10.1186/s10020-018-0032-7 PMID: 30134816
  65. Vallianou, N.G.; Evangelopoulos, A.; Schizas, N.; Kazazis, C. Potential anticancer properties and mechanisms of action of curcumin. Anticancer Res., 2015, 35(2), 645-651. PMID: 25667441
  66. Tang, S.M.; Deng, X.T.; Zhou, J.; Li, Q.P.; Ge, X.X.; Miao, L. Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects. Biomed. Pharmacother., 2020, 121, 109604. doi: 10.1016/j.biopha.2019.109604 PMID: 31733570
  67. Varoni, E.M.; Lo Faro, A.F.; Sharifi-Rad, J.; Iriti, M. Anticancer molecular mechanisms of resveratrol. Front. Nutr., 2016, 3, 8. doi: 10.3389/fnut.2016.00008 PMID: 27148534
  68. Fu, Y.; Chang, H.; Peng, X.; Bai, Q.; Yi, L.; Zhou, Y.; Zhu, J.; Mi, M. Resveratrol inhibits breast cancer stem-like cells and induces autophagy via suppressing Wnt/β-catenin signaling pathway. PLoS One, 2014, 9(7), e102535. doi: 10.1371/journal.pone.0102535 PMID: 25068516
  69. Seo, H.S.; Ku, J.M.; Choi, H.S.; Choi, Y.K.; Woo, J.K.; Kim, M.; Kim, I.; Na, C.H.; Hur, H.; Jang, B.H.; Shin, Y.C.; Ko, S.G. Quercetin induces caspase-dependent extrinsic apoptosis through inhibition of signal transducer and activator of transcription 3 signaling in HER2-overexpressing BT-474 breast cancer cells. Oncol. Rep., 2016, 36(1), 31-42. doi: 10.3892/or.2016.4786 PMID: 27175602
  70. Das, M.; Manna, K. Chalcone scaffold in anticancer armamentarium: A molecular insight. J. Toxicol., 2016, 2016, 7651047.
  71. Cascão, R.; Fonseca, J.E.; Moita, L.F. Celastrol: A spectrum of treatment opportunities in chronic diseases. Front. Med., 2017, 4, 69. doi: 10.3389/fmed.2017.00069 PMID: 28664158
  72. Xiong, J.; Li, J.; Yang, Q.; Wang, J.; Su, T.; Zhou, S. Gossypol has anti-cancer effects by dual-targeting MDM2 and VEGF in human breast cancer. Breast Cancer Res., 2017, 19(1), 27. doi: 10.1186/s13058-017-0818-5 PMID: 28274247
  73. Pons, D.G.; Nadal-Serrano, M.; Torrens-Mas, M.; Valle, A.; Oliver, J.; Roca, P. UCP2 inhibition sensitizes breast cancer cells to therapeutic agents by increasing oxidative stress. Free Radic. Biol. Med., 2015, 86, 67-77. doi: 10.1016/j.freeradbiomed.2015.04.032 PMID: 25960046
  74. Peiró, G.; Ortiz-Martínez, F.; Gallardo, A.; Pérez-Balaguer, A.; Sánchez-Payá, J.; Ponce, J.J.; Tibau, A.; López-Vilaro, L.; Escuin, D.; Adrover, E.; Barnadas, A.; Lerma, E. Src, a potential target for overcoming trastuzumab resistance in HER2-positive breast carcinoma. Br. J. Cancer, 2014, 111(4), 689-695. doi: 10.1038/bjc.2014.327 PMID: 24937674
  75. Bernard, M.M.; McConnery, J.R.; Hoskin, D.W. 10-Gingerol, a major phenolic constituent of ginger root, induces cell cycle arrest and apoptosis in triple-negative breast cancer cells. Exp. Mol. Pathol., 2017, 102(2), 370-376. doi: 10.1016/j.yexmp.2017.03.006 PMID: 28315687
  76. Deep, G.; Agarwal, R. Antimetastatic efficacy of silibinin: Molecular mechanisms and therapeutic potential against cancer. Cancer Metastasis Rev., 2010, 29(3), 447-463. doi: 10.1007/s10555-010-9237-0 PMID: 20714788
  77. Jiang, K.; Wang, W.; Jin, X.; Wang, Z.; Ji, Z.; Meng, G. Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells. Oncol. Rep., 2015, 33(6), 2711-2718. doi: 10.3892/or.2015.3915 PMID: 25891311
  78. Hasanzadeh, M.; Samarghandian, S.; Azimi-Nezhad, M.; Borji, A.; Jabbari, F.; Farkhondeh, T.; Samini, M. Inhibitory and cytotoxic activities of chrysin on human breast adenocarcinoma cells by induction of apoptosis. Pharmacogn. Mag., 2016, 12(47)(Suppl. 4), 436. doi: 10.4103/0973-1296.191453 PMID: 27761071
  79. Huang, W.W.; Tsai, S.C.; Peng, S.F.; Lin, M.W.; Chiang, J.H.; Chiu, Y.J.; Fushiya, S.; Tseng, M.T.; Yang, J.S. Kaempferol induces autophagy through AMPK and AKT signaling molecules and causes G2/M arrest via downregulation of CDK1/cyclin B in SK-HEP-1 human hepatic cancer cells. Int. J. Oncol., 2013, 42(6), 2069-2077. doi: 10.3892/ijo.2013.1909 PMID: 23591552
  80. Lee, G.A.; Choi, K.C.; Hwang, K.A. Kaempferol, a phytoestrogen, suppressed triclosan-induced epithelial-mesenchymal transition and metastatic-related behaviors of MCF-7 breast cancer cells. Environ. Toxicol. Pharmacol., 2017, 49, 48-57. doi: 10.1016/j.etap.2016.11.016 PMID: 27902959
  81. Lu, L.; Guo, Q.; Zhao, L. Overview of oroxylin A: A promising flavonoid compound. Phytother. Res., 2016, 30(11), 1765-1774. doi: 10.1002/ptr.5694 PMID: 27539056
  82. Shen, M.; Guo, M.; Wang, Z.; Li, Y.; Kong, D.; Shao, J.; Tan, S.; Chen, A.; Zhang, F.; Zhang, Z.; Zheng, S. ROS-dependent inhibition of the PI3K/Akt/mTOR signaling is required for Oroxylin A to exert anti-inflammatory activity in liver fibrosis. Int. Immunopharmacol., 2020, 85, 106637. doi: 10.1016/j.intimp.2020.106637 PMID: 32512269
  83. Xu, H.; Zhang, S. Scutellarin-induced apoptosis in HepG2 hepatocellular carcinoma cells via a STAT3 pathway. Phytother. Res., 2013, 27(10), 1524-1528. doi: 10.1002/ptr.4892 PMID: 23192830
  84. Trejo-Solís, C.; Pedraza-Chaverrí, J.; Torres-Ramos, M.; Jiménez-Farfán, D.; Cruz, S.A.; Serrano-García, N. Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition. Evid. Based Complement Alternat. Med., 2013, 2013, 705121. doi: 10.1155/2013/705121
  85. Bimonte, S.; Albino, V.; Piccirillo, M.; Nasto, A.; Molino, C.; Palaia, R.; Cascella, M. Epigallocatechin-3-gallate in the prevention and treatment of hepatocellular carcinoma: Experimental findings and translational perspectives. Drug Des. Devel. Ther., 2019, 13, 611-621. doi: 10.2147/DDDT.S180079 PMID: 30858692
  86. Wang, Z.; Shen, G.; Xie, J.; Li, B.; Gao, Q. Rottlerin upregulates DDX3 expression in hepatocellular carcinoma. Biochem. Biophys. Res. Commun., 2018, 495(1), 1503-1509. doi: 10.1016/j.bbrc.2017.11.198 PMID: 29203243
  87. Park, H.J.; Jeon, Y.K.; You, D.H.; Nam, M.J. Daidzein causes cytochrome c-mediated apoptosis via the Bcl-2 family in human hepatic cancer cells. Food Chem. Toxicol., 2013, 60, 542-549. doi: 10.1016/j.fct.2013.08.022 PMID: 23959101
  88. Magee, P.J.; Allsopp, P.; Samaletdin, A.; Rowland, I.R. Daidzein, R-(+)equol and S-(−)equol inhibit the invasion of MDA-MB-231 breast cancer cells potentially via the down-regulation of matrix metalloproteinase-2. Eur. J. Nutr., 2014, 53(1), 345-350. doi: 10.1007/s00394-013-0520-z PMID: 23568763
  89. Koo, J.; Cabarcas-Petroski, S.; Petrie, J.L.; Diette, N.; White, R.J.; Schramm, L. Induction of proto-oncogene BRF2 in breast cancer cells by the dietary soybean isoflavone daidzein. BMC Cancer, 2015, 15(1), 905. doi: 10.1186/s12885-015-1914-5 PMID: 26573593
  90. Hu, S.; Huang, L.; Meng, L.; Sun, H.; Zhang, W.; Xu, Y. Isorhamnetin inhibits cell proliferation and induces apoptosis in breast cancer via Akt and mitogen-activated protein kinase kinase signaling pathways. Mol. Med. Rep., 2015, 12(5), 6745-6751. doi: 10.3892/mmr.2015.4269 PMID: 26502751
  91. Fang, D.; Xiong, Z.; Xu, J.; Yin, J.; Luo, R. Chemopreventive mechanisms of galangin against hepatocellular carcinoma: A review. Biomed. Pharmacother., 2019, 109, 2054-2061. doi: 10.1016/j.biopha.2018.09.154 PMID: 30551461
  92. Su, L.; Chen, X.; Wu, J.; Lin, B.; Zhang, H.; Lan, L.; Luo, H. Galangin inhibits proliferation of hepatocellular carcinoma cells by inducing endoplasmic reticulum stress. Food Chem. Toxicol., 2013, 62, 810-816. doi: 10.1016/j.fct.2013.10.019 PMID: 24161691
  93. Lewandowska, U.; Szewczyk, K.; Owczarek, K.; Hrabec, Z.; Podsędek, A.; Sosnowska, D.; Hrabec, E. Procyanidins from evening primrose (Oenothera paradoxa) defatted seeds inhibit invasiveness of breast cancer cells and modulate the expression of selected genes involved in angiogenesis, metastasis, and apoptosis. Nutr. Cancer, 2013, 65(8), 1219-1231. doi: 10.1080/01635581.2013.830314 PMID: 24099118
  94. Garcia, A.; Zheng, Y.; Zhao, C.; Toschi, A.; Fan, J.; Shraibman, N.; Brown, H.A.; Bar-Sagi, D.; Foster, D.A.; Arbiser, J.L. Honokiol suppresses survival signals mediated by Ras-dependent phospholipase D activity in human cancer cells. Clin. Cancer Res., 2008, 14(13), 4267-4274. doi: 10.1158/1078-0432.CCR-08-0102 PMID: 18594009
  95. Avtanski, D.B.; Nagalingam, A.; Bonner, M.Y.; Arbiser, J.L.; Saxena, N.K.; Sharma, D. Honokiol inhibits epithelial—mesenchymal transition in breast cancer cells by targeting signal transducer and activator of transcription 3/Zeb1/E‐cadherin axis. Mol. Oncol., 2014, 8(3), 565-580. doi: 10.1016/j.molonc.2014.01.004 PMID: 24508063
  96. Wang, N.; Wang, Z.Y.; Mo, S.L.; Loo, T.Y.; Wang, D.M.; Luo, H.B.; Yang, D.P.; Chen, Y.L.; Shen, J.G.; Chen, J.P. Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer. Breast Cancer Res. Treat., 2012, 134(3), 943-955. doi: 10.1007/s10549-012-1977-9 PMID: 22350787
  97. Sun, G.; Zhang, S.; Xie, Y.; Zhang, Z.; Zhao, W. Gallic acid as a selective anticancer agent that induces apoptosis in SMMC-7721 human hepatocellular carcinoma cells. Oncol. Lett., 2016, 11(1), 150-158. doi: 10.3892/ol.2015.3845 PMID: 26870182
  98. Chen, Y.C.; Yang, L.L.; Lee, T.J.F. Oroxylin A inhibition of lipopolysaccharide-induced iNOS and COX-2 gene expression via suppression of nuclear factor-κB activation. Biochem. Pharmacol., 2000, 59(11), 1445-1457. doi: 10.1016/S0006-2952(00)00255-0 PMID: 10751555
  99. Nahum, A.; Hirsch, K.; Danilenko, M.; Watts, C.K.W.; Prall, O.W.J.; Levy, J.; Sharoni, Y. Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27Kip1 in the cyclin E–cdk2 complexes. Oncogene, 2001, 20(26), 3428-3436. doi: 10.1038/sj.onc.1204452 PMID: 11423993
  100. Garcia-Oliveira, P.; Otero, P.; Pereira, A.G.; Chamorro, F.; Carpena, M.; Echave, J.; Fraga-Corral, M.; Simal-Gandara, J.; Prieto, M.A. Status and challenges of plant-anticancer compounds in cancer treatment. Pharmaceuticals, 2021, 14(2), 157. doi: 10.3390/ph14020157 PMID: 33673021
  101. Choudhari, A.S.; Mandave, P.C.; Deshpande, M.; Ranjekar, P.; Prakash, O. Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Front. Pharmacol., 2020, 10, 1614. doi: 10.3389/fphar.2019.01614 PMID: 32116665
  102. Jafri, A.; Amjad, S.; Bano, S.; Kumar, S.; Serajuddin, M.; Arshad, M. Efficacy of nano-phytochemicals over pure phytochemicals against various cancers: current trends and future prospects. In: Nanomaterials and Environmental Biotechnology; Springer, 2020; pp. 407-424.
  103. Tauro, S.; Dhokchawle, B.; Mohite, P.; Nahar, D.; Nadar, S.; Coutinho, E. Natural anticancer agents: Their therapeutic potential, challenges and promising outcomes. Curr. Med. Chem., 2024, 31(7), 848-870. doi: 10.2174/0929867330666230502113150 PMID: 37138435
  104. Melfi, F.; Carradori, S.; Mencarelli, N.; Campestre, C.; Gallorini, M.; Di Giacomo, S.; Di Sotto, A. Natural products as a source of new anticancer chemotypes. Expert Opin. Ther. Pat., 2023, 33(11), 721-744. doi: 10.1080/13543776.2023.2265561 PMID: 37775999
  105. Alharbi, K.S.; Almalki, W.H.; Makeen, H.A.; Albratty, M.; Meraya, A.M.; Nagraik, R.; Sharma, A.; Kumar, D.; Chellappan, D.K.; Singh, S.K.; Dua, K.; Gupta, G. Role of medicinal plant‐derived nutraceuticals as a potential target for the treatment of breast cancer. J. Food Biochem., 2022, 46(12), e14387. doi: 10.1111/jfbc.14387 PMID: 36121313
  106. Thilagavathi, R.; Begum, S.S.; Varatharaj, S.D.; Balasubramaniam, A.; George, J.S.; Selvam, C. Recent insights into the hepatoprotective potential of medicinal plants and plant-derived compounds. Phytother. Res., 2023, 37(5), 2102-2118. doi: 10.1002/ptr.7821 PMID: 37022281
  107. Twaij, B.M.; Hasan, M.N. Bioactive secondary metabolites from plant sources: Types, synthesis, and their therapeutic uses. Int. J. Plant Biol., 2022, 13(1), 4-14. doi: 10.3390/ijpb13010003
  108. Wawrosch, C.; Zotchev, S.B. Production of bioactive plant secondary metabolites through in vitro technologies—status and outlook. Appl. Microbiol. Biotechnol., 2021, 105(18), 6649-6668. doi: 10.1007/s00253-021-11539-w PMID: 34468803

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 Bentham Science Publishers