The Role of Natural Products in Managing Hepatocellular Carcinoma

Gehan F Abdel Raoof1,*, Moaaz A Ali Abuaish2

1Pharmacognosy Department, Pharmaceutical and Drug Research Industries Division, National Research Centre, Dokki, Giza 12622, Egypt.
2College of Biotechnology, Misr University for Science and Technology (MUST), Egypt.

Abstract: Objective: Hepatocellular carcinoma (HCC) is the most occurring cancer worldwide, responsible for approximately 1000000 deaths annually. There are many ways for the treatment of HCC such as; resection, liver transplantation, sorafenib and chemoembolization. Although all the previous treatments for hepatocellular carcinoma are good and may be fast but these methods are expensive and have many complications, so all the world is going to produce new drugs from natural origins to avoid these complications. Herbal medicine has become a very safe, non-toxic, and easily available source of cancer-treating compounds. Herbs are believed to neutralize the effects of diseases in a body because of various characteristics they possess. Although all the previous treatments for hepatocellular carcinoma are good and may be fast in their effects but it is more expensive and have many complications, so all the world is going to produce new drugs from natural origins and plants to avoid these complications A number of medicinal plants showed a cytotoxic effect on hepatocellular carcinoma due to the presence of bioactive secondary metabolites. Aim: This review aims to illustrate the role of natural products and their major bioactive constituents in the treatment of hepatocellular carcinoma, and discusses the possible mechanisms of action, to be used instead of synthetic medications which combined with undesired complications. Results: The current review showed that medicinal plants play a vital role in the management of hepatocellular carcinoma due to the presence of diversity of phytoconstituents that exert their effect via different mechanisms of action.


Keywords:Hepatocellular carcinoma, medicinal plants, cytotoxic, bioactive.

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References:
  1. Alnajjar A M,ElsiesyH A.Natural products and hepatocellular carcinoma: a review. Hepatoma Research 2015;1:119-24.
  2. Tomimatsu M, IshiguroN,TaniaiM, OkudaH, SaitoA, ObataH,YamamofoM,Takasaki K, NakanoM.Hepatitis C Virus Antibody in Patients with Primary Liver Cancer (Hepatocellular Carcinoma, Cholangiocarcinoma, and Combined Hepatocellular-Cholangiocarcinoma) in Japan. Cancer 1993;72:683-8.
  3. Jemal A, BrayF, Center M,et al.Global cancer statistics.Cancer J Clin 2011; 61: 69-90.
  4. El-Serag HB.Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology, European Association for the Study of the liver. Eur J Cancer 2012;142: 1264-73.
  5. Zhao C, NguyenM H.Hepatocellular Carcinoma Screening and Surveillance.J Clin Gastroenterol 2016;50:120–33.
  6. TangA, HallouchO,Chernyak V, Kamaya A,SirlinC B.Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis. Abdom Radiol 2018;43:13–25.
  7. Neamatallah M, El-BendaryM,ElalfyH,BesheerT, El-MaksoudM A,Elhammady D, et al. Impact of toll-like receptors 2(TLR2) and TLR 4 gene variations on HCV susceptibility, response to treatment and development of hepatocellular carcinoma in cirrhotic HCV patients.J MolCell Immunol 2019;48:1–15.
  8. Ledda C, LoretoC, ZammitC, MarconiA,FagoL, MateraS,et al.Noninfective occupational risk factors for hepatocellular carcinoma: A review. Mol Med Rep 2017;15:511–33.
  9. Schütte K,BornscheinJ,MalfertheinerP.Hepatocellular carcinoma -epidemiological trends and risk factors. Dig Dis Sci 2009; 27:80–92.
  10. Abdel-Rahman O, Helbling D, SchöbO, EltobgyM, Mohamed H, Schmidt J, et al. Cigarette smoking as a risk factor for the development of and mortality from hepatocellular carcinoma: an updated systematic review of 81 epidemiological studies. J Evid Based Med 2017;10:245–54.
  11. Ziada D H, El SadanyS,SolimanH, Abd-ElsalamS,SalamaM,Hawash N,et al. Prevalence of hepatocellular carcinoma in chronic hepatitis C patients in Mid Delta, Egypt: a single center study. JENCI 2016;28: 257–62.
  12. Dimitroulis D,Damaskos C,ValsamiS, DavakisS, GarmpisN, Spartalis E et al. From diagnosis to treatment of hepatocellular carcinoma: an epidemic problem for both developed and developing world. World J Gastroenterol 2017;23:5282–94.
  13. SingalAG, El-SeragH B.Hepatocellular carcinoma from epidemiology to prevention: translating knowledge into practice. J Clin Gastroenterol Hepatol 2015;13:2140–51.
  14. Khan T , Ali M, Khan A, NisarP, Jan S A, Afridi S,ShinwariZ K. Anticancer Plants: A Review of the Active Phytochemicals, Applications in Animal Models, and Regulatory Aspects. Biomolecules2020;10(1): 1-30.
  15. Rozefelds A, DettmannM, CliffordT,HocknullS, NewmanN,GodthelpH,et al.Traditional and computed tomographic (CT) techniques link modern and Cenozoic fruits of Pleiogynium (Anacardiaceae) from Australia. Alcheringa2015;39(1):24-39.
  16. Lin W, Zhao J,Cao Z, ZhuangQ, Zheng L, CaiQ, Chen D, Wang L, Hong Z, PengJ. Livistonachinensisseed suppresses hepatocellular carcinoma growth through promotion of mitochondrial-dependent apoptosis. Oncol Rep2013; 29:1859-66.
  17. Hong Z, ChenW,ZhaJ, Wu Z, Zhou J, Li T, HuJ.Hepatoprotective effects of RubusaleaefoliusPoir and identification of its active constituents. J Ethnopharmacol 2010;129:267-72.
  18. Lee J H, HamY A, ChoiS H, ImE O, Jung J H, ImK S, Kim D K, Xu Y, Wang M W, KimN D.Activity of crude extract of Rubuscrataegifolius roots as a potent apoptosis inducer and DNA topoisomerase I inhibitor. Arch Pharm Res2000; 23:338-43.
  19. Xue H, AzizR M, SunN, CassadyJ M, KamendulisL M, Xu Y,Stoner G D,Klaunig J E. Inhibition of cellular transformation by berry extracts. Carcinogenesis2001; 22:351-6.
  20. Zhao J, Chen X, Lin W, Wu G, ZhuangQ,ZhongX, Hong Z, Peng J. Total alkaloids of RubusaleaefoliusPoir inhibit hepatocellular carcinoma growth in vivo and in vitro via activation of mitochondrial-dependent apoptosis.IntJ Oncol2013;42:971-8.
  21. Devi B,SharmaN, KumarD,JeetK, LinnM A.A phytopharmacological review. Int J Pharm Pharm Sci2013;5: 14–8.
  22. Naowaratwattana W, De-EknamkulW, De MejiaE G.Phenolic-containing organic extracts of mulberry (Morus alba L.) leaves inhibit HepG2 hepatoma cells through G2/M phase arrest, induction of apoptosis, and inhibition of topoisomerase II_ activity. J Med Food 2010;13:1045–56.
  23. Suh S J, YoonJ W, LeeT K, JinU H, KimS L, Kim M S, KwonDY, Lee Y C, KimC H.Chemoprevention of Scutellariabardata on human cancer cells and tumorigenesis in skin cancer. Phytother Res 2007;21:135–41.
  24. Zhang Y, Liang Y, HeC.Anticancer activities and mechanisms of heat-clearing and detoxicating traditional Chinese herbal medicine. Chin Med J 2017;12:1-15.
  25. Lin C S,KuoC L, Wang J P, ChengJ S,W.HuangZ, ChenC F.Growth inhibitory and apoptosisinducing effect of Perillafrutescens extract on human hepatoma HepG2 cells. J Ethnopharmacol 2007; 112: 557–67.
  26. Abdel Raoof G F, SaidA A, MohamedK Y,GomaaH A.Phytoconstituents and bioactivities of the bark of Pleiogyniumtimorense (DC.) Leenh (Anacardiaceae). J Herbmed Pharmacol 2020; 9:20-7.
  27. Jacob L,LathaM S. Anticancer activity of Clitoriaternatea Linn. against Dalton’s lymphoma. Int J Pharmacognosy and Phytochem Res 2012;4(4): 207-12.
  28. Zhong Z G, ZhaoS Y, LvJ Y, Li P. Experimental study on antitumor effect of extracts from Cestrum nocturnum in vivo. Zhong Yao Cai2008; 31: 1709-12.
  29. Tawfeeq A T, HassanI H, KadhimH M,Abdul HaffidZ T.Convolvulus scammonia crude alkaloids extract induces apoptosis through microtubules destruction in mice hepatoma H22 cell line.Iraqi J Cancer Med Genet2012;5:134-46.
  30. Pacifico S,GallicchioM,FiorentinoA, FischerA, Meyer U,StintzingF C.Antioxidant properties and cytotoxic effects on human cancer cell lines of aqueous fermented and lipophilic quince (Cydonia oblonga Mill.) preparations. Food Chem Toxicol 2012; 50:4130-5.
  31. Al-SnafiA E.The medical importance of Cydonia oblonga- A review.IOSR J Pharm2016; 6: 87-99.
  32. Said A A , El GendyM A M, Abdel RaoofG F, OmerE A, FouadR,Abd EL-Kader A E, WeinfeldM.Cytotoxic activity and volatile components of peel oil of Citrus volkameriana. S Afr J Bot 2019;127:201-7.
  33. Sun Y., TaoW, Huang H, SunX P.Flavonoids, phenolic acids, carotenoids and antioxidant activity of fresh eating citrus fruits, using the coupled in vitro digestion and human intestinal HepG2 cells model. J Food Chem 2019; 279: 321–7.
  34. Armentano M F, Bisaccia F, Miglionico R, Russo D, Nolfi N, Carmosino M, et al. Antioxidant and Proapoptotic Activities of Sclerocaryabirrea [(A. Rich.) Hochst.]Methanolic Root Extract on the Hepatocellular Carcinoma Cell Line HepG2.Biomed Res Int 2015; 2015:1-11.
  35. Tanih N F,Ndip R N.The acetone extract of Sclerocaryabirrea (Anacardiaceae) possesses antiproliferative and apoptotic potential against human breast cancer cell lines (MCF-7). SciWorld J 2013;2013:1-7.
  36. Pinmai K, ChunlaratthanabhornS, Ngamkitidechakul C,SoonthornchareonN,HahnvajanawongC. Synergistic growth inhibitory effects of Phyllanthusemblica and Terminalia bellerica extracts with conventional cytotoxic agents: Doxorubicin and cisplatin against human hepatocellular carcinoma and lung cancer cells. World J Gastroenterol 2008;14:1491-7.