Thymoquinone in Cancers Therapy: Comparison
Please note this is a comparison between Version 2 by Bruce Ren and Version 1 by BELAL ALMAJALI.

To date, natural products are widely used as pharmaceutical agents for many human diseases and cancers. One of the most popular natural products that have been studied for anticancer properties is thymoquinone (TQ). As a bioactive compound of Nigella sativa, TQ has shown anticancer activities through the inhibition of cell proliferation, migration, and invasion. The anticancer efficacy of TQ is being investigated in several human cancers such as pancreatic cancer, breast cancer, colon cancer, hepatic cancer, cervical cancer, and leukemia.

  • thymoquinone
  • cancers
  • proliferation
  • apoptosis
  • angiogenesis
  • nanoparticle
Please wait, diff process is still running!

References

  1. Imran, M.; Rauf, A.; Khan, I.A.; Shahbaz, M.; Qaisrani, T.B.; Fatmawati, S.; Abu-Izneid, T.; Imran, A.; Rahman, K.U.; Gondal, T.A. Thymoquinone: A novel strategy to combat cancer: A review. Biomed. Pharmacother. 2018, 106, 390–402.
  2. Ahmad, N.; Ahmad, R.; Al-Layly, A.; Al-Shawi, H.; Al-Ali, A.; Amir, M.; Mostafa, A. Ultra-high-performance liquid chro-matography-based identification and quantification of thymoquinone in Nigella sativa extract from different geographical re-gions. Pharmacogn. Mag. 2018, 14, 471.
  3. Awad, A.S.M.; Al Haleem, E.N.A.; El-Bakly, W.M.; Sherief, M.A. Thymoquinone alleviates nonalcoholic fatty liver disease in rats via suppression of oxidative stress, inflammation, apoptosis. Naunyn-Schmiedeberg’s Arch. Pharmacol. 2016, 389, 381–391.
  4. Ebrahimi, S.S.; Oryan, S.; Izadpanah, E.; Hassanzadeh, K. Thymoquinone exerts neuroprotective effect in animal model of Parkinson’s disease. Toxicol. Lett. 2017, 276, 108–114.
  5. Abulfadl, Y.S.; El-Maraghy, N.N.; Ahmed, A.E.; Nofal, S.; Abdel-Mottaleb, Y.; Badary, A.O. Thymoquinone alleviates the experimentally induced Alzheimer’s disease inflammation by modulation of TLRs signaling. Hum. Exp. Toxicol. 2018, 37, 1092–1104.
  6. Ecevit, H.; Gunduz, K.; Bilgic, N.; Izmirli, M.; Gogebakan, B. The effect of thymoquinone on BEAS-2B cell viability and TGF-β1 release. AMOR 2017, 3, 15–19.
  7. Khan, A.; Tania, M.; Fu, S.; Fu, J. Thymoquinone, as an anticancer molecule: From basic research to clinical investigation. Oncotarget 2017, 8, 51907–51919.
  8. Khan, M.D.; Tania, M.; Wei, C.; Mei, Z.; Fu, S.; Cheng, J.; Xu, J.; Fu, J. Thymoquinone inhibits cancer metastasis by downreg-ulating TWIST1 expression to reduce epithelial to mesenchymal transition. Oncotarget 2015, 6, 19580.
  9. Pang, J.; Shen, N.; Yan, F.; Zhao, N.; Dou, L.; Wu, L.-C.; Seiler, C.L.; Yu, L.; Yang, K.; Bachanova, V.; et al. Thymoquinone exerts potent growth-suppressive activity on leukemia through DNA hypermethylation reversal in leukemia cells. Oncotarget 2017, 8, 34453–34467.
  10. Barkat, M.D.; Ahmad, J.; Khan, M.A.; Beg, S.; Ahmad, F.J. Insights into the targeting potential of thymoquinone for therapeu-tic intervention against triple-negative breast cancer. Curr. Drug Targets 2018, 19, 70–80.
  11. Samarghandian, S.; Azimi-Nezhad, M.; Farkhondeh, T. Thymoquinone-induced antitumor and apoptosis in human lung adenocarcinoma cells. J. Cell. Physiol. 2019, 234, 10421–10431.
  12. Martinovich, G.G.; Martinovich, I.V.; Vcherashniaya, A.V.; Shadyro, O.I.; Cherenkevich, S.N. Thymoquinone, a biologically active component of Nigella sativa, induces mitochondrial production of reactive oxygen species and programmed death of tumor cells. Biophys. 2016, 61, 963–970.
  13. Hsu, H.-H.; Chen, M.-C.; Day, C.H.; Lin, Y.-M.; Li, S.-Y.; Tu, C.-C.; Padma, V.V.; Shih, H.-N.; Kuo, W.-W.; Huang, C.-Y. Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activa-tion. World J. Gastroenterol. 2017, 23, 1171.
  14. Taha, E.M.M.; Sheikh, B.Y.; Salim, A.L.Z.; Mohan, S.; Khan, A.; Kamalidehghan, B.; Ahmadipour, F.; I Abdelwahab, S. Thymoquinone induces apoptosis and increase ROS in ovarian cancer cell line. Cell. Mol. Boil. 2016, 62, 97–101.
  15. Sarman, H.; Bayram, R.; Benek, S.B. Anticancer drugs with chemotherapeutic interactions with thymoquinone in osteosar-coma cells. Eur. Rev. Med. Pharmacol. Sci. 2016, 20, 1263–1270.
  16. Ahmad, A.; Mishra, R.K.; Vyawahare, A.; Kumar, A.; Rehman, M.U.; Qamar, W.; Khan, A.Q.; Khan, R. Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects. Saudi Pharm. J. 2019, 27, 1113–1126.
  17. Zhu, W.-Q.; Wang, J.; Guo, X.-F.; Liu, Z.; Dong, W.-G. Thymoquinone inhibits proliferation in gastric cancer via the STAT3 pathway in vivo and in vitro. World J. Gastroenterol. 2016, 22, 4149.
  18. Upadhyay, P.; Sarker, S.; Ghosh, A.; Gupta, P.; Das, S.; Ahir, M.; Bhattacharya, S.; Chattopadhyay, S.; Ghosh, S.; Adhikary, A. Transferrin-decorated thymoquinone-loaded PEG-PLGA nanoparticles exhibit anticarcinogenic effect in non-small cell lung carcinoma via the modulation of miR-34a and miR-16. Biomater. Sci. 2019, 7, 4325–4344.
  19. Ali, B.H.; Blunden, G. Pharmacological and toxicological properties of Nigella sativa. Phytother. Res. 2003, 17, 299–305.
  20. Salem, M.L. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int. Immunopharmacol. 2005, 5, 1749–1770.
  21. Salmani, J.M.; Asghar, S.; Lv, H.; Zhou, J. Aqueous solubility and degradation kinetics of the phytochemical anticancer thy-moquinone; probing the effects of solvents, pH and light. Molecules 2014, 19, 5925–5939.
  22. Darakhshan, S.; Pour, A.B.; Colagar, A.H.; Sisakhtnezhad, S. Thymoquinone and its therapeutic potentials. Pharmacol. Res. 2015, 95–96, 138–158.
  23. Nagi, M.N.; Almakki, H.A. Thymoquinone supplementation induces quinone reductase and glutathione transferase in mice liver: Possible role in protection against chemical carcinogenesis and toxicity. Phytotherapy Res. 2009, 23, 1295–1298.
  24. Rahmani, A.H.; Alzohairy, M.A.; Khan, M.A.; Aly, S.M. Therapeutic implications of black seed and its constituent thymo-quinone in the prevention of cancer through inactivation and activation of molecular pathways. Evid. Based Complement Alternat. Med. 2014, 2014.
  25. Mansour, M.A.; Ginawi, O.T.; El-Hadiyah, T.; El-Khatib, A.S.; Al-Shabanah, O.A.; Al-Sawaf, H.A. Effects of volatile oil con-stituents of Nigella sativa on carbon tetrachloride-induced hepatotoxicity in mice: Evidence for antioxidant effects of thymo-quinone. Res. Commun. Mol. Pathol. Pharmacol. 2001, 110, 239–252.
  26. Kanter, M. Thymoquinone attenuates lung injury induced by chronic toluene exposure in rats. Toxicol. Ind. Heal. 2010, 27, 387–395.
  27. Jain, A.; Pooladanda, V.; Bulbake, U.; Doppalapudi, S.; Rafeeqi, T.A.; Godugu, C.; Khan, W. Liposphere mediated topical delivery of thymoquinone in the treatment of psoriasis. Nanomed. Nanotechnol. Biol. Med. 2017, 13, 2251–2262.
  28. Zaher, N.H.; Rashed, E.R.; El-Ghazaly, M.A. Semi-synthetic thymoquinone analogs: New prototypes as potential antihyper-lipidemics in irradiated rats. Future Med. Chem. 2017, 9, 1483–1493.
  29. Johnson-Ajinwo, O.R.; Ullah, I.; Mbye, H.; Richardson, A.; Horrocks, P.; Li, W.-W. The synthesis and evaluation of thymo-quinone analogues as anti-ovarian cancer and antimalarial agents. Bioorg. Med. Chem. Lett. 2018, 28, 1219–1222.
  30. Glamočlija, U.; Padhye, S.; Špirtović-Halilović, S.; Osmanović, A.; Veljović, E.; Roca, S.; Novakovic, I.; Mandic, B.; Turel, I.; Kljun, J.; et al. Synthesis, biological evaluation and docking studies of benzoxazoles derived from thymoquinone. Molecules 2018, 23, 3297.
  31. Lupidi, G.; Scire, A.; Camaioni, E.; Khalife, K.H.; De Sanctis, G.; Tanfani, F.; Damiani, E. Thymoquinone, a potential thera-peutic agent of Nigella sativa, binds to site I of human serum albumin. Phytomedicine 2010, 17, 714–720.
  32. El-Najjar, N.; Ketola, R.A.; Nissilä, T.; Mauriala, T.; Antopolsky, M.; Jänis, J.; Gali-Muhtasib, H.; Urtti, A.; Vuorela, H. Impact of protein binding on the analytical detectability and anticancer activity of thymoquinone. J. Chem. Biol. 2011, 4, 97–107.
  33. Bhattacharya, S.; Ahir, M.; Patra, P.; Mukherjee, S.; Ghosh, S.; Mazumdar, M.; Chattopadhyay, S.; Das, T.; Chattopadhyay, D.; Adhikary, A. PEGylated-thymoquinone-nanoparticle mediated retardation of breast cancer cell migration by deregulation of cytoskeletal actin polymerization through miR-34a. Biomaterials 2015, 51, 91–107.
  34. Kumari, S.; Mg, S.; Mayor, S. Endocytosis unplugged: Multiple ways to enter the cell. Cell Res. 2010, 20, 256–275.
  35. Dinarvand, R.; Sepehri, N.; Manouchehri; Rouhani, H.; Atyabi, F. Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents. Int. J. Nanomed. 2011, 6, 877–895.
  36. Ballout, F.; Habli, Z.; Rahal, O.N.; Fatfat, M.; Gali-Muhtasib, H. Thymoquinone-based nanotechnology for cancer therapy: Promises and challenges. Drug Discov. Today 2018, 23, 1089–1098.
  37. Ganea, G.M.; Fakayode, S.O.; Losso, J.N.; Van Nostrum, C.F.; Sabliov, C.M.; Warner, I.M. Delivery of phytochemical thy-moquinone using molecular micelle modified poly (D, L lactide-co-glycolide)(PLGA) nanoparticles. Nanotechnology 2010, 21, 285104.
  38. Sun, H.; Guo, B.; Cheng, R.; Meng, F.; Liu, H.; Zhong, Z. Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin. Biomaterials 2009, 30, 6358–6366.
  39. Shah, M.; Choi, M.H.; Ullah, N.; Kim, M.O.; Yoon, S.C. Synthesis and characterization of PHV-block-mPEG diblock copoly-mer and its formation of amphiphilic nanoparticles for drug delivery. J. Nanosci. Nanotechnol. 2011, 11, 5702–5710.
  40. Mona, M.A.; Mottaleb, A. Biodegradable thymoquinone nanoparticles for higher therapeutic efficiency in murine colorectal cancer. Int. J. Pharm. Pharm. Res. 2016, 7, 436–450.
  41. Del Valle, E. Cyclodextrins and their uses: A review. Process. Biochem. 2004, 39, 1033–1046.
  42. Abu-Dahab, R.; Odeh, F.; Ismail, S.I.; Azzam, H.; Al Bawab, A. Preparation, characterization and antiproliferative activity of thymoquinone-β-cyclodextrin self-assembling nanoparticles. Pharmazie 2013, 68, 939–944.
  43. Wang, T.; Luo, Y. Biological fate of ingested lipid-based nanoparticles: Current understanding and future directions. Nanoscale 2019, 11, 11048–11063.
  44. Akbarzadeh, A.; Rezaei-Sadabady, R.; Davaran, S.; Joo, S.W.; Zarghami, N.; Hanifehpour, Y.; Samiei, M.; Kouhi, M.; Nejati-Koshki, K. Liposome: Classification, preparation, and applications. Nanoscale Res. Lett. 2013, 8, 102.
  45. Gregoriadis, G. Engineering liposomes for drug delivery: Progress and problems. Trends Biotechnol. 1995, 13, 527–537.
  46. Odeh, F.; Ismail, S.I.; Abu-Dahab, R.; Mahmoud, I.S.; Al Bawab, A. Thymoquinone in liposomes: A study of loading efficiency and biological activity towards breast cancer. Drug Deliv. 2012, 19, 371–377.
  47. Durak, S.; Rad, M.E.; Yetisgin, A.A.; Sutova, H.E.; Kutlu, O.; Cetinel, S.; Zarrabi, A. Niosomal Drug Delivery Systems for Ocular Disease—Recent Advances and Future Prospects. Nanomaterials 2020, 10, 1191.
  48. Moghassemi, S.; Hadjizadeh, A. Nano-niosomes as nanoscale drug delivery systems: An illustrated review. J. Control. Release 2014, 185, 22–36.
  49. Rajput, S.; Puvvada, N.; Kumar, B.N.; Sarkar, S.; Konar, S.; Bharti, R.; Dey, G.; Mazumdar, A.; Pathak, A.; Fisher, P.B. Overcoming Akt induced therapeutic resistance in breast cancer through siRNA and thymoquinone encapsulated multila-mellar gold niosomes. Mol. Pharm. 2015, 12, 4214–4225.
  50. Üner, M. Characterization and Imaging of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers. Handb. Nanoparticles 2016, 117–141.
  51. Singh, A.; Ahmad, I.; Akhter, S.; Jain, G.K.; Iqbal, Z.; Talegaonkar, S.; Ahmad, F.J. Nanocarrier based formulation of Thy-moquinone improves oral delivery: Stability assessment, in vitro and in vivo studies. Colloids Surf. B 2013, 102, 822–832.
  52. Surekha, R.; Aishwarya, V.; Sumathi, T. Thymoquinone loaded solid lipid nanoparticle: Formulation, characterization and in-vitro cell viability assay. Int. J. Pharm. Bio. Sci. 2014, 6, 449–464.
  53. Badawy, M.E.; Rabea, E.I. A biopolymer chitosan and its derivatives as promising antimicrobial agents against plant patho-gens and their applications in crop protection. Int. J. Carbohydr. Chem. 2011, 2011.
  54. Cheba, B.A. Chitin and chitosan: Marine biopolymers with unique properties and versatile applications. Glob. J. Biotechnol. Biochem. 2011, 6, 149–153.
  55. Othman, N.; Masarudin, M.J.; Kuen, C.Y.; Dasuan, N.A.; Abdullah, L.C. Synthesis and optimization of chitosan nanoparti-cles loaded with L-ascorbic acid and thymoquinone. Nanomaterials 2018, 8, 920.
  56. Alam, S.; Khan, Z.I.; Mustafa, G.; Kumar, M.; Islam, F.; Bhatnagar, A.; Ahmad, F.J. Development and evaluation of thymo-quinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: A pharmacoscintigraphic study. Int. J. Nanomed. 2012, 7, 5705.
  57. Talib, W.H. Regressions of Breast Carcinoma Syngraft Following Treatment with Piperine in Combination with Thymoquinone. Sci. Pharm. 2017, 85, 27.
  58. Dastjerdi, M.N.; Mehdiabady, E.M.; Iranpour, F.G.; Bahramian, H. Effect of thymoquinone on P53 gene expression and con-sequence apoptosis in breast cancer cell line. Int. J. Prev. Med. 2016, 7.
  59. Yıldırım, I.H.; Azzawri, A.A.; Duran, T. Thymoquinone induces apoptosis via targeting the Bax/BAD and Bcl-2 pathway in breast cancer cells. Dicle Tıp Derg. 2019, 46, 411–417.
  60. Fatfat, M.; Fakhoury, I.; Habli, Z.; Mismar, R.; Gali-Muhtasib, H. Thymoquinone enhances the anticancer activity of doxoru-bicin against adult T-cell leukemia in vitro and in vivo through ROS-dependent mechanisms. Life Sci. 2019, 232, 116628.
  61. Shanmugam, M.K.; Hsu, A.; Hui, K.M.; Tan, B.K.; Sethi, G. Abstract 4123: Thymoquinone inhibits bone metastasis in a breast cancer mouse model by modulating CXCR4/CXCL12 signaling axis. Tumor Biology 2016, 76, 4123.
  62. Bhattacharya, S.; Ghosh, A.; Maiti, S.; Ahir, M.; Debnath, G.H.; Gupta, P.; Bhattacharjee, M.; Ghosh, S.; Chattopadhyay, S.; Mukherjee, P. Delivery of thymoquinone through hyaluronic acid-decorated mixed Pluronic® nanoparticles to attenuate an-giogenesis and metastasis of triple-negative breast cancer. J. Control. Release 2020, 322.
  63. Kabil, N.; Bayraktar, R.; Kahraman, N.; Mokhlis, H.A.; Calin, G.A.; Lopez-Berestein, G.; Ozpolat, B. Thymoquinone inhibits cell proliferation, migration, and invasion by regulating the elongation factor 2 kinase (eEF-2K) signaling axis in tri-ple-negative breast cancer. Breast Cancer Res. Treat. 2018, 171, 593–605.
  64. Şakalar, Ç.; İzgi, K.; İskender, B.; Sezen, S.; Aksu, H.; Çakır, M.; Kurt, B.; Turan, A.; Canatan, H. The combination of thy-moquinone and paclitaxel shows anti-tumor activity through the interplay with apoptosis network in triple-negative breast cancer. Tumor Biol. 2016, 37, 4467–4477.
  65. Chang, Y.; Yan, W.; Sun, C.; Liu, Q.; Wang, J.; Wang, M. miR‑145‑5p inhibits epithelial‑mesenchymal transition via the JNK signaling pathway by targeting MAP3K1 in non‑small cell lung cancer cells. Oncol. Lett. 2017, 14, 6923–6928.
  66. Yang, J.; Kuang, X.-R.; Lv, P.-T.; Yan, X.-X. Thymoquinone inhibits proliferation and invasion of human nonsmall-cell lung cancer cells via ERK pathway. Tumor Biol. 2014, 36, 259–269.
  67. Alhakamy, N.A.; Badr-Eldin, S.M.; A Fahmy, U.; Alruwaili, N.K.; Awan, Z.A.; Caruso, G.; Alfaleh, M.A.; Alaofi, A.L.; Arif, F.O.; Ahmed, A.A. Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells. Pharmaceutics 2020, 12, 761.
  68. Hussein, S.A.; Abdel-Aal, S.A.; Amin, A.; Khalaf, H.A. Caspase-3, Bcl-2, p53, CYP1A1 and COX-2 as a potential target in chemoprevention of Benzo (a) pyrene-induced lung carcinogenesis in mice: Role of thymoquinone. Nat. Sci. 2016, 4, 430–441.
  69. Dera, A.A.; Rajagopalan, P.; Al Fayi, M.; Ahmed, I.; Chandramoorthy, H.C. Indirubin-3-monoxime and thymoquinone ex-hibit synergistic efficacy as therapeutic combination in in-vitro and in-vivo models of Lung cancer. Arch. Pharm. Res. 2020, 43, 655–665.
  70. Singh, S.K.; Mishra, M.K.; Lillard, J.W.; Singh, R. Thymoquinone enhanced the tumoricidal activity of NK Cells against Lung Cancer. Am. Assoc. Immnol. 2018, 200, 124.5.
  71. Wilson, A.J.; Saskowski, J.; Barham, W.; Yull, F.; Khabele, D. Thymoquinone enhances cisplatin-response through direct tu-mor effects in a syngeneic mouse model of ovarian cancer. J. Ovarian Res. 2015, 8, 46.
  72. Pazhouhi, M.; Sariri, R.; Rabzia, A.; Khazaei, M. Thymoquinone synergistically potentiates temozolomide cytotoxicity through the inhibition of autophagy in U87MG cell line. Iran. J. Basic. Med. Sci. 2016, 19, 890–898.
  73. Bitarafan, S.; Yari, M.; Broumand, M.A.; Ghaderian, S.M.H.; Rahimi, M.; Mirfakhraie, R.; Azizi, F.; Omrani, M.D. Association of Increased Levels of lncRNA H19 in PBMCs with Risk of Coronary Artery Disease. Cell J. 2018, 20, 564–568.
  74. Khalife, R.; Hodroj, M.H.; Fakhoury, R.; Rizk, S. Thymoquinone from Nigella sativa Seeds Promotes the Antitumor Activity of Noncytotoxic Doses of Topotecan in Human Colorectal Cancer Cells in Vitro. Planta Med. 2016, 82, 312–321.
  75. Dirican, A.; Atmaca, H.; Bozkurt, E.; Erten, C.; Karaca, B.; Uslu, R. Novel combination of docetaxel and thymoquinone in-duces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K–AKT pathway. Clin. Transl. Oncol. 2015, 17, 145–151.
  76. Imani, S.; Wei, C.; Cheng, J.; Khan, A.; Fu, S.; Yang, L.; Tania, M.; Zhang, X.; Xiao, X.; Zhang, X.; et al. MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion. Oncotarget 2017, 8, 21362–21379.
  77. Feng, L.-M.; Wang, X.-F.; Huang, Q.-X. Thymoquinone induces cytotoxicity and reprogramming of EMT in gastric cancer cells by targeting PI3K/Akt/mTOR pathway. J. Biosci. 2017, 42, 547–554.
  78. Ma, J.; Hu, X.; Li, J.; Wu, D.; Lan, Q.; Wang, Q.; Tian, S.; Dong, W. Enhancing conventional chemotherapy drug cispla-tin-induced anti-tumor effects on human gastric cancer cells both in vitro and in vivo by thymoquinone targeting PTEN gene. Oncotarget 2017, 8, 85926.
  79. Chen, M.-C.; Lee, N.-H.; Hsu, H.-H.; Ho, T.-J.; Tu, C.-C.; Hsieh, D.J.-Y.; Lin, Y.-M.; Chen, L.-M.; Kuo, W.-W.; Huang, C.-Y. Thymoquinone Induces Caspase-Independent, Autophagic Cell Death in CPT-11-Resistant LoVo Colon Cancer via Mitochondrial Dysfunction and Activation of JNK and p38. J. Agric. Food Chem. 2015, 63, 1540–1546.
  80. Froehlich, T.; Ndreshkjana, B.; Muenzner, J.K.; Reiter, C.; Hofmeister, E.; Mederer, S.; Fatfat, M.; El-Baba, C.; Gali-Muhtasib, H.; Schneider-Stock, R. Synthesis of novel hybrids of thymoquinone and artemisinin with high activity and selec-tivity against colon cancer. ChemMedChem 2017, 12, 226–234.
  81. Chen, M.-C.; Lee, N.-H.; Hsu, H.; Ho, T.-J.; Tu, C.; Chen, R.-J.; Lin, Y.; Viswanadha, V.P.; Kuo, W.-W.; Huang, C.-Y. Inhibition of NF-κB and metastasis in irinotecan (CPT-11)-resistant LoVo colon cancer cells by thymoquinone via JNK and p38. Environ. Toxicol. 2016, 32, 669–678.
  82. Zhang, L.; Bai, Y.; Yang, Y. Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB. Oncol. Lett. 2016, 12, 2840–2845.
  83. Mohamed, A.M.; Refaat, B.A.; El-Shemi, A.G.; Kensara, O.A.; Ahmad, J.; Idris, S. Thymoquinone potentiates chemoprotec-tive effect of Vitamin D3 against colon cancer: A pre-clinical finding. Am. J. Transl. Res. 2017, 9, 774.
  84. Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2016. CA A Cancer J. Clin. 2016, 66, 7–30.
  85. Kou, B.; Liu, W.; Zhao, W.; Duan, P.; Yang, Y.; Yi, Q.; Guo, F.; Li, J.; Zhou, J.; Kou, Q. Thymoquinone inhibits epitheli-al-mesenchymal transition in prostate cancer cells by negatively regulating the TGF-β/Smad2/3 signaling pathway. Oncol. Rep. 2017, 38, 3592–3598.
  86. Singh, S.K.; Lillard Jr, J.W.; Singh, R. Thymoquinone regulates cytochrome P450 genes involved in prostate cancer disparity. Cancer Epidemiol. Biomark. Prev. 2018.
  87. Singh, S.K.; Apata, T.; Gordetsky, J.B.; Singh, R. Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway. Cancers 2019, 11, 1390.
  88. Al-Trad, B.; Al-Zoubi, M.; Qar, J.; Al-Batayneh, K.; Hussien, E.; Muhaidat, R.; Aljabali, A.; Alkhateeb, H.; Al Omari, G. In-hibitory effect of thymoquinone on testosterone-induced benign prostatic hyperplasia in Wistar rats. Phytother. Res. 2017, 31, 1910–1915.
  89. Ranjbari, A.; Heidarian, E.; Ghatreh-Samani, K. Effects of Thymoquinone on IL-6 Gene Expression and Some Cellular Signaling Pathways in Prostate Cancer PC3 Cells. Jundishapur J. Nat. Pharm. Prod. 2017, 12.
  90. Park, J.E.; Kim, D.-H.; Ha, E.; Choi, S.M.; Choi, J.-S.; Chun, K.-S.; Joo, S.H. Thymoquinone induces apoptosis of human epi-dermoid carcinoma A431 cells through ROS-mediated suppression of STAT3. Chem. Biol. Interact. 2019, 312, 108799.
  91. Jeong, H.; Yu, S.; Kim, S.J. Inhibitory effects on melanogenesis by thymoquinone are mediated through the β‑catenin pathway in B16F10 mouse melanoma cells. Int. J. Oncol. 2019, 56, 379–389.
  92. Ren, X.; Luo, W. Exploration of pro-apoptotic effect of Thymoquinone on oral squamous cell carcinoma cells through PI3K/Akt signaling pathway. Cell. Mol. Biol. 2019, 65, 61–64.
  93. Hatiboglu, M.A.; Koçyiğit, A.; Guler, E.M.; Akdur, K.; Nalli, A.; Karatas, E.; Tüzgen, S. Thymoquinone Induces Apoptosis in B16-F10 Melanoma Cell Through Inhibition of p-STAT3 and Inhibits Tumor Growth in a Murine Intracerebral Melanoma Model. World Neurosurg. 2018, 114, e182–e190.
  94. Hatiboglu, M.A.; Kocyigit, A.; Guler, E.M.; Akdur, K.; Khan, I.; Nalli, A.; Karatas, E.; Tuzgen, S. Thymoquinone Enhances the Effect of Gamma Knife in B16-F10 Melanoma Through Inhibition of Phosphorylated STAT3. World Neurosurg. 2019, 128, e570–e581.
  95. Ha, J.H.; Jayaraman, M.; Radhakrishnan, R.; Gomathinayagam, R.; Yan, M.; Song, Y.S.; Isidoro, C.; Dhanasekaran, D.N. Differential effects of thymoquinone on lysophosphatidic acid-induced oncogenic pathways in ovarian cancer cells. J. Tradit. Complement. Med. 2020, 10, 207–216.
  96. Liu, X.; Dong, J.; Cai, W.; Pan, Y.; Li, R.; Li, B. The Effect of Thymoquinone on Apoptosis of SK-OV-3 Ovarian Cancer Cell by Regulation of Bcl-2 and Bax. Int. J. Gynecol. Cancer 2017, 27, 1596–1601.
  97. İnce, I.; Yıldırım, Y.; Güler, G.; Medine, E.I.; Ballıca, G.; Kuşdemir, B.C.; Göker, E. Synthesis and characterization of folic ac-id-chitosan nanoparticles loaded with thymoquinone to target ovarian cancer cells. J. Radioanal. Nucl. Chem. 2020, 324, 1–15.
  98. Johnson-Ajinwo, O.R.; Richardson, A.; Li, W.-W. Synthesis and evaluation of thymoquinone analogues as anti-ovarian can-cer agents. MDPI 2019, 22, 42.
  99. Alhassani, M.Y.; Zohny, S.F.; Sheikh, R.A.; Hassan, M.A.; Kalantan, A.A.; Hosawi, S.; Alhosin, M. Thymoquinone exerts anti-tumor activities on human hepatocellular carcinoma cells: Role of angiogenesis-related genes VCAN, Grb2 and EZH2. Eur. J. Cell Sci. 2019, 10–16.
  100. Meral, I.; Pala, M.; Akbas, F.; Ustunova, S.; Yildiz, C.; Demirel, M. Effects of thymoquinone on liver miRNAs and oxidative stress in Ehrlich acid mouse solid tumor model. Biotech. Histochem. 2018, 93, 301–308.
  101. Helmy, S.A.; El-Mesery, M.; El-Karef, A.; Eissa, L.A.; El Gayar, A.M. Thymoquinone upregulates TRAIL/TRAILR2 expression and attenuates hepatocellular carcinoma in vivo model. Life Sci. 2019, 233, 116673.
  102. Haron, A.S.; Syed Alwi, S.S.; Saiful Yazan, L.; Abd Razak, R.; Ong, Y.S.; Zakarial Ansar, F.H.; Roshini Alexander, H. Cyto-toxic effect of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) on liver cancer cell integrated with hepatitis B genome, Hep3B. Evid. Based Complement Alternat. Med. 2018.
  103. Bashir, A.O.; El-Mesery, M.E.; Anwar, R.; Eissa, L.A. Thymoquinone potentiates miR-16 and miR-375 expressions in hepato-cellular carcinoma. Life Sci. 2020, 117794.
  104. Butt, A.S.; Nisar, N.; Ghani, N.; Altaf, I.; Mughal, T.A. Isolation of thymoquinone from Nigella sativa L. and Thymus vulgaris L., and its anti-proliferative effect on HeLa cancer cell lines. Trop. J. Pharm. Res. 2019, 18, 37.
  105. Li, J.; Khan, A.; Wei, C.; Cheng, J.; Chen, H.; Yang, L.; Ijaz, I.; Fu, J. Thymoquinone Inhibits the Migration and Invasive Characteristics of Cervical Cancer Cells SiHa and CaSki In Vitro by Targeting Epithelial to Mesenchymal Transition Associated Transcription Factors Twist1 and Zeb1. Molecules 2017, 22, 2105.
  106. Ng, W.K.; Saiful Yazan, L.; Yap, L.H.; Wan, N.H.; Wan, A.G.; How, C.W.; Abdullah, R. Thymoquinone-loaded nanostruc-tured lipid carrier exhibited cytotoxicity towards breast cancer cell lines (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa). BioMed Res. Int. 2015.
  107. Houssein, M.; Fatfat, M.; Habli, Z.; Ghazal, N.; Mokdad, S.; Khalife, H.; Khalil, M.; Gali-Muhtasib, H. Thymoquinone syner-gizes with arsenic and interferon alpha to target human T-cell leukemia/lymphoma. Life Sci. 2020, 117639.
  108. Musalli, M.G.; Hassan, M.A.; Sheikh, R.A.; Kalantan, A.A.; Halwani, M.A.; Zeyadi, M.; Hosawi, S.; Alhosin, M. Thymo-quinone induces cell proliferation inhibition and apoptosis in acute myeloid leukemia cells: Role of apoptosis-related WT1 and BCL2 genes. Eur. J. Cell Sci. 2019, 1, 2–9.
  109. Alaufi, O.M.; Noorwali, A.; Zahran, F.; Al-Abd, A.M.; Al-Attas, S. Cytotoxicity of thymoquinone alone or in combination with cisplatin (CDDP) against oral squamous cell carcinoma in vitro. Sci. Rep. 2017, 7, 13131.
  110. Kotowski, U.; Heiduschka, G.; Kadletz, L.; Fahim, T.; Seemann, R.; Schmid, R.; Schneider, S.; Mitterbauer, A.; Thurnher, D. Effect of thymoquinone on head and neck squamous cell carcinoma cells in vitro: Synergism with radiation. Oncol. Lett. 2017, 14, 1147–1151.
More
Video Production Service