Skip to main content
SpringerLink
Log in

Anticancer Action of Thymoquinone

  • Chapter
  • First Online:
Molecular and Therapeutic actions of Thymoquinone

Abstract

Thymoquinone (TQ) is a biologically active compound found in the Nigella sativa and extensively studied over the decades for its implications in diseases management without promoting the adverse side effects. An extensive number of researches have been performed to evaluate the efficacy of TQ in killing of cancer cells through modulating several biological activities, which play a vital role in the pathogenesis of cancer. Moreover, TQ shows an important role in the induction of apoptosis as well as cell cycle arrest in cancerous cells through the upregulation of PTEN gene and cyclin-dependent kinase inhibitor. A novel molecular target of TQ against numerous cancerous cells or inhibition of cancer growth is the modulation of protein kinase, nuclear factor kappa B, angiogenesis and tumorigenesis. Although numerous studies based on animal model and laboratory research have been performed to assess the potentiality of TQ in cancer prevention, chemopreventive role of TQ in humans is still unexplored. However, detailed and appropriate studies are needed to authenticate the role of TQ as a future drug therapy in the management of cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdelfadil E, Cheng YH, Bau DT et al (2013) Thymoquinone induces apoptosis in oral cancer cells through p38β inhibition. Am J Chin Med 41(3):683–696

    Article  CAS  Google Scholar 

  • AbuKhader MM (2012) The effect of route of administration in thymoquinone toxicity in male and female rats. Indian J Pharm Sci 74(3):195–200

    Article  CAS  Google Scholar 

  • Acharya BR, Chatterjee A, Ganguli A et al (2014) Thymoquinone inhibits microtubule polymerization by tubulin binding and causes mitotic arrest following apoptosis in A549 cells. Biochimie 97:78–91

    Article  CAS  Google Scholar 

  • Ahmad A, Khan RM, Alkharfy KM et al (2015) Thymoquinone on the pharmacokinetics and pharmacodynamics of glibenclamide in a rat model. Nat Prod Commun 10(8):1395–1398

    PubMed  Google Scholar 

  • Al-Ali A, Alkhawajah AA, Randhawa MA et al (2008) Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J Ayub Med Coll Abbottabad 20:25–27

    PubMed  Google Scholar 

  • Al-Amri AM, Bamosa AO (2009) Phase I safety and clinical activity study of thymoquinone in patients with advanced refractory malignant disease. Shiraz E-Med J 10(3):107–111

    Google Scholar 

  • Alhosin M, Ibrahim A, Boukhari A et al (2012) Anti-neoplastic agent thymoquinone induces degradation of alpha and beta tubulin proteins in human cancer cells without affecting their level in normal human fibroblasts. Investig New Drugs 30:1813–1819

    Article  CAS  Google Scholar 

  • Ali Salim LZ, Othman R, Abdulla MA et al (2014) Thymoquinone inhibits murine leukemia WEHI-3 cells in vivo and in vitro. PLoS One 9(12):e115340

    Article  Google Scholar 

  • Arafa el SA, Zhu Q, Shah ZI et al (2011) Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells. Mutat Res 706:28–35

    Article  Google Scholar 

  • Ashour AE, Abd-Allah AR, Korashy HM et al (2014) Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis. Mol Cell Biochem 389:85–98

    Article  CAS  Google Scholar 

  • Attoub S, Sperandio O, Raza H et al (2013) Thymoquinone as an anticancer agent: evidence from inhibition of cancer cells viability and invasion in vitro and tumor growth in vivo. Fundam Clin Pharmacol 27(5):557–569

    Article  CAS  Google Scholar 

  • Badary O, Al-Shabanah O, Nagi M et al (1998) Acute and subchronic toxicity of thymoquinone in mice. Drug Dev Res 44:56–61

    Article  Google Scholar 

  • Badr G, Mohany M, Abu-Tarboush F (2011) Thymoquinone decreases F-actin polymerization and the proliferation of human multiple myeloma cells by suppressing STAT3 phosphorylation and Bcl2/Bcl-XL expression. Lipids Health Dis 10:236

    Article  CAS  Google Scholar 

  • Banerjee S, Kaseb AO, Wang Z et al (2009) Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res 69(13):5575–5583

    Article  CAS  Google Scholar 

  • Bhattacharya S, Ahir M, Patra P et al (2015) PEGylated-thymoquinone-nanoparticle mediated retardation of breast cancer cell migration by deregulation of cytoskeletal actin polymerization through miR-34a. Biomaterials 51:91–107

    Article  CAS  Google Scholar 

  • Boyle P, Levin BE (eds) (2008) World cancer report. IARC. IARC Press, Lyon

    Google Scholar 

  • Chehl N, Chipitsyna G, Gong Q et al (2009) Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells. HPB (Oxford) 11(5):373–381

    Article  Google Scholar 

  • Chu SC, Hsieh YS, Yu CC et al (2014) Thymoquinone induces cell death in human squamous carcinoma cells via caspase activation-dependent apoptosis and LC3-II activation-dependent autophagy. PLoS One 9:e101579

    Article  Google Scholar 

  • Collins K, Mitchell JR (2002) Telomerase in the human organism. Oncogene 21(4):564–579

    Article  CAS  Google Scholar 

  • Das S, Dey KK, Dey G et al (2012) Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma. PLoS One 7:e46641

    Article  CAS  Google Scholar 

  • Dastjerdi D, Mehdiabady E, Iranpour F et al (2016) Effect of thymoquinone on P53 gene expression and consequence apoptosis in breast cancer cell line. Int J preventative med 7(1):66–71

    Article  Google Scholar 

  • Di Cristofano A, Pandolfi PP (2000) The multiple roles of PTEN in tumor suppression. Cell 100:387–390

    Article  Google Scholar 

  • Dirican A, Erten C, Atmaca H et al (2014) Enhanced cytotoxicity and apoptosis by thymoquinone in combination with zoledronic acid in hormone- and drug-resistant prostate cancer cell lines. Journal of BUON: official journal of the Balkan Union of. Oncology 19(4):1055–1061

    Google Scholar 

  • El Mezayen R, El Gazzar M, Nicolls MR et al (2006) Effect of thymoquinone on cyclooxygenase expression and prostaglandin production in a mouse model of allergic airway inflammation. Immunol Lett 106:72–81

    Article  Google Scholar 

  • Elbarbry F, Ragheb A, Marfleet T et al (2012) Modulation of hepatic drug metabolizing enzymes by dietary doses of thymoquinone in female New Zealand white rabbits. Phytother Res 26(11):1726–1730

    Article  CAS  Google Scholar 

  • ElKhoely A, Hafez HF, Ashmawy AM et al (2015) Chemopreventive and therapeutic potentials of thymoquinone in HepG2 cells: mechanistic perspectives. J Nat Med 69(3):313–323

    Article  CAS  Google Scholar 

  • El-Mahdy MA, Zhu Q, Wang QE et al (2005) Thymoquinone induces apoptosis through activation of caspase-8 and mitochondrial events in p53-null myeloblastic leukemia HL-60 cells. Int J Cancer 117(3):409–417

    Article  CAS  Google Scholar 

  • El-Najjar N, Chatila M, Moukadem H et al (2010) Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling. Apoptosis 15(2):183–195

    Article  CAS  Google Scholar 

  • El-Sheikh AA, Morsy MA, Abdalla AM et al (2015) Mechanisms of thymoquinone hepatorenal protection in methotrexateinduced toxicity in rats. Mediat Inflamm 2015:859383

    Article  Google Scholar 

  • Fathy M, Nikaido T (2013) In vivo modulation of iNOS pathway in hepatocellular carcinoma by Nigella sativa. Environ Health Prev Med 18:377–385

    Article  CAS  Google Scholar 

  • Furnari FB, Huang HJ, Cavenee WK (1998) The phosphoinositol phosphatase activity of PTEN mediates a serum-sensitive G1 growth arrest in glioma cells. Cancer Res 58:5002–5008

    CAS  PubMed  Google Scholar 

  • Gali-Muhtasib H, Diab-Assaf M, Boltze C et al (2004a) Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism. Int J Oncol 25(4):857–866

    CAS  PubMed  Google Scholar 

  • Gali-Muhtasib HU, Abou Kheir WG, Kheir LA et al (2004b) Molecular pathway for thymoquinone-induced cell-cycle arrest and apoptosis in neoplastic keratinocytes. Anti-Cancer Drugs 15(4):389–399

    Article  CAS  Google Scholar 

  • Gali-Muhtasib H, Kuester D, Mawrin C et al (2008) Thymoquinone triggers inactivation of the stress response pathway sensor CHEK1 and contributes to apoptosis in colorectal cancer cells. Cancer Res 68:5609–5618

    Article  CAS  Google Scholar 

  • Gurung RL, Lim SN, Khaw AK et al (2010) Thymoquinone induces telomere shortening, DNA damage and apoptosis in human glioblastoma cells. PLoS One 5(8):e12124

    Article  Google Scholar 

  • Harari PM, Allen GW, Bonner JA (2007) Biology of interactions: antiepidermal growth factor receptor agents. J Clin Oncol 25:4057–4065

    Article  CAS  Google Scholar 

  • Hosseinzadeh H, Parvardeh S, Asl MN et al (2007) Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine 14(9):621–627

    Article  CAS  Google Scholar 

  • Kabel AM, El-Rashidy MA, Omar MS (2016) Ameliorative potential of tamoxifen/thymoquinone combination in patients with breast cancer: a biochemical and immunohistochemical study. Cancer Med Anticancer Drug 1:102

    Google Scholar 

  • Kaseb AO, Chinnakannu K, Chen D et al (2007) Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Cancer Res 67(16):7782–7788

    Article  CAS  Google Scholar 

  • Kensara OA, El-Shemi AG, Mohamed AM et al (2016) Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats. Drug Des Devel Ther 10:2239–2253

    Article  CAS  Google Scholar 

  • Kundu J, Choi BY, Jeong CH et al (2014) Thymoquinone induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2- and Src mediated phosphorylation of EGF receptor tyrosine kinase. Oncol Rep 32(2):821–828

    Article  Google Scholar 

  • Lang M, Borgmann M, Oberhuber G et al (2013) Thymoquinone attenuates tumor growth in ApcMin mice by interference with Wnt-signaling. Mol Cancer 12(1):41

    Article  CAS  Google Scholar 

  • Laskar AA, Khan MA, Rahmani AH et al (2016) Thymoquinone, an active constituent of Nigella sativa seeds, binds with bilirubin and protects mice from hyperbilirubinemia and cyclophosphamide-induced hepatotoxicity. Biochimie 127:205–213

    Article  CAS  Google Scholar 

  • Lei X, Lv X, Liu M et al (2012) Thymoquinone inhibits growth and augments 5-fluorouracil-induced apoptosis in gastric cancer cells both in vitro and in vivo. Biochem Biophys Res Commun 417(2):864–868

    Article  CAS  Google Scholar 

  • Li F, Rajendran P, Sethi G (2010) Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway. Br J Pharmacol 161:541–554

    Article  CAS  Google Scholar 

  • Motaghed M, Al-Hassan FM, Hamid SS (2013) Cellular responses with thymoquinone treatment in human breast cancer cell line MCF-7. Pharm Res 5(3):200–206

    Google Scholar 

  • Mu HQ, Yang S, Wang YJ et al (2012) Role of NF-κB in the anti-tumor effect of thymoquinone on bladder cancer. Zhonghua Yi Xue Za Zhi 92:392–396

    CAS  PubMed  Google Scholar 

  • Ng WK, Yazan LS, Ismail M (2011) Thymoquinone from Nigella sativa was more potent than cisplatin in eliminating of SiHa cells via apoptosis with down-regulation of Bcl-2 protein. Toxicol In Vitro 25(7):1392–1398

    Article  CAS  Google Scholar 

  • Normanno N, De Luca A, Bianco C et al (2006) Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366:2–16

    Article  CAS  Google Scholar 

  • Odeh F, Odeh F, Ismail SI et al (2012) Thymoquinone in liposomes: a study of loading efficiency and biological activity towards breast cancer. Drug Deliv 19(8):371–377

    Article  CAS  Google Scholar 

  • Ohnishi Y, Lieger O, Attygalla M et al (2008) Effects of epidermal growth factor on the invasion activity of the oral cancer cell lines HSC3 and SAS. Oral Oncol 44:1155–1159

    Article  CAS  Google Scholar 

  • Paramasivam A, Sambantham S, Shabnam J et al (2012) Anti-cancer effects of thymoquinone in mouse neuroblastoma (Neuro-2a) cells through caspase-3 activation with down-regulation of XIAP. Toxicol Lett 213(2):151–159

    Article  CAS  Google Scholar 

  • Peng L, Liu A, Shen Y et al (2013) Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma through the NF-κB pathway. Oncol Rep 29(2):571–578

    Article  CAS  Google Scholar 

  • Raghunandhakumar S, Paramasivam A, Senthilraja S et al (2013) Thymoquinone inhibits cell proliferation through regulation of G1/S phase cell cycle transition in N-nitrosodiethylamine-induced experimental rat hepatocellular carcinoma. Toxicol Lett 223(1):60–72

    Article  CAS  Google Scholar 

  • Rahmani AH, Aly SM (2015) Nigella sativa and its active constituent thymoquinone shows pivotal role in the diseases prevention and treatment. Asian J Pharm Clin Res 8:48–53

    CAS  Google Scholar 

  • Rahmani A, Alzohairy M, Khadri H et al (2012) Expressional evaluation of vascular endothelial growth factor (VEGF) protein in urinary bladder carcinoma patients exposed to cigarette smoke. Int J Clin Exp Pathol 5:195–202

    PubMed  PubMed Central  Google Scholar 

  • Rahmani AH, Shabrmi FM, Aly SM (2014a) Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities. Int J Physiol Pathophysiol Pharmacol 6:125–136

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rahmani AH, Al Zohairy MA, Aly SM et al (2014b) Curcumin: a potential candidate in prevention of cancer via modulation of molecular pathways. Biomed Res Int 2014:761608

    Article  Google Scholar 

  • Rahmani AH, Al Shabrmi FM, Allemailem KS et al (2015) Implications of green tea and its constituents in the prevention of cancer via the modulation of cell signalling pathway. Biomed Res Int 2015:2015

    Google Scholar 

  • Rajput S, Kumar BN, Dey KK et al (2013) Molecular targeting of Akt by thymoquinone promotes G (1) arrest through translation inhibition of cyclin D1 and induces apoptosis in breast cancer cells. Life Sci 93(21):783–790

    Article  CAS  Google Scholar 

  • Rajput S, Kumar BN, Banik P et al (2015) Thymoquinone restores radiation-induced TGF-β expression and abrogates EMT in chemoradiotherapy of breast cancer cells. J Cell Physiol 230(3):620–629

    Article  CAS  Google Scholar 

  • Sakalar C, Yuruk M, Kaya T et al (2013) Pronounced transcriptional regulation of apoptotic and TNF-NF-kappa-B signaling genes during the course of thymoquinone mediated apoptosis in HeLa cells. Mol Cell Biochem 383(1–2):243–251

    Article  CAS  Google Scholar 

  • Salim LZ, Mohan S, Othman R et al (2013) Thymoquinone induces mitochondria-mediated apoptosis in acute lymphoblastic leukaemia in vitro. Molecules 18(9):11219–11240

    Article  CAS  Google Scholar 

  • Salmena L, Carracedo A, Pandolfi PP et al (2008) Tenets of PTEN tumor suppression. Cell 133:403–414

    Article  CAS  Google Scholar 

  • Sayed-Ahmed MM, Aleisa AM, Al-Rejaie SS et al (2010) Thymoquinone attenuates diethylnitrosamine induction of hepatic carcinogenesis through antioxidant signaling. Oxidative Med Cell Longev 3:254–261

    Article  Google Scholar 

  • Sethi G, Ahn KS, Aggarwal BB (2008) Targeting nuclear factor-kappa B activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis. Mol Cancer Res 6:1059–1070

    Article  CAS  Google Scholar 

  • Shoieb AM, Elgayyar M, Dudrick PS et al (2003) In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone. Int J Oncol 22(1):107–113

    CAS  PubMed  Google Scholar 

  • Stewart BW, Wild CP (eds) (2014) Cancer etiology. World cancer report. World Health Organization. ISBN: 9283204298

    Google Scholar 

  • Taketo MM (1998) Cyclooxygenase-2 inhibitors in tumorigenesis (part II). J Natl Cancer Inst 90:1609–1620

    Article  CAS  Google Scholar 

  • Taylor WR, Stark GR (2001) Regulation of the G2/M transition by p53. Oncogene 20:1803–1815

    Article  CAS  Google Scholar 

  • Taysi S, Uslu C, Akcay F et al (2003) MDA and nitric oxide in the plasma of patients with advanced laryngeal cancer. Surg Today 33(9):651–654

    Article  CAS  Google Scholar 

  • Thomson LL, Lawton FG, Knowles RG et al (1994) NO synthase activity in human gynecological cancer. Cancer Res 54:1352–1354

    Google Scholar 

  • Torres MP, Ponnusamy MP, Chakraborty S et al (2010) Effects of thymoquinone in the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel cancer therapies. Mol Cancer Ther 9(5):1419–1431

    Article  CAS  Google Scholar 

  • Ulasli SS, Celik S, Gunay E et al (2013) Anticancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol on A549 non-small cell lung cancer cells exposed to benzo(a)pyrene. Asian Pac J Cancer Prev 14(10):6159–6164

    Article  Google Scholar 

  • Umar S, Zargan J, Umar K et al (2012) Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chem Biol Interact 197(1):40–46

    Article  CAS  Google Scholar 

  • Waggoner SE (2003) Cervical cancer. Lancet 361(9376):2217–2225

    Article  Google Scholar 

  • Wang X, Jiang X (2008) PTEN: a default gate-keeping tumor suppressor with a versatile tail. Cell Res 18:807–816

    Article  CAS  Google Scholar 

  • Wilson AJ, Saskowski J, Barham W et al (2015) Microenvironmental effects limit efficacy of thymoquinone treatment in a mouse model of ovarian cancer. Mol Cancer 14:192

    Article  Google Scholar 

  • Wirries A, Breyer S, Quint K et al (2010) Thymoquinone hydrazone derivatives cause cell cycle arrest in p53-competent colorectal cancer cells. Exp Ther Med 1:369–375

    Article  CAS  Google Scholar 

  • Woo CC, Loo SY, Gee V et al (2011) Anticancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR-γ pathway. Biochem Pharmacol 82(5):464–475

    Article  CAS  Google Scholar 

  • Woo CC, Kumar AP, Sethi G et al (2012) Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 83(4):443–451

    Article  CAS  Google Scholar 

  • Woo CC, Hsu A, Kumar AP et al (2013) Thymoquinone inhibits tumor growth and induces apoptosis in a breast cancer xenograft mouse model: the role of p38 MAPK and ROS. PLoS One 8(10):e75356

    Article  CAS  Google Scholar 

  • Wu ZH, Chen Z, Shen Y et al (2011) Anti-metastasis effect of thymoquinone on human pancreatic cancer. Yao Xue Xue Bao 46(8):910–914

    CAS  PubMed  Google Scholar 

  • Yang J, Kuang XR, Lv PT et al (2015) Thymoquinone inhibits proliferation and invasion of human nonsmall-cell lung cancer cells via ERK pathway. Tumour Biol 36(1):259–269

    Article  Google Scholar 

  • Yi T, Cho SG, Yi Z et al (2008) Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways. Mol Cancer Ther 7(7):1789–1796

    Article  CAS  Google Scholar 

  • Yu SM, Kim SJ (2013) Thymoquinone-induced reactive oxygen species causes apoptosis of chondrocytes via PI3K/Akt and p38kinase pathway. Exp Biol Med (Maywood) 238:811–820

    Article  Google Scholar 

  • Zhang L, Bai Y, Yang Y (2016) Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB. Oncol Lett 12(4):2840–2845

    Article  CAS  Google Scholar 

  • Zhu W, Wang J, Guo X et al (2016) Thymoquinone inhibits proliferation in gastric cancer via the STAT3 pathway in vivo and in vitro. World J Gastroenterol 22(16):4149–4159

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia

    Arshad H. Rahmani

Authors
  1. Arshad H. Rahmani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arshad H. Rahmani .

Editor information

Editors and Affiliations

  1. Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

    Hina Younus

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Rahmani, A.H. (2018). Anticancer Action of Thymoquinone. In: Younus, H. (eds) Molecular and Therapeutic actions of Thymoquinone. Springer, Singapore. https://doi.org/10.1007/978-981-10-8800-1_3

Download citation

Publish with us

Policies and ethics

Search

Navigation