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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
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
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
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
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
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
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
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
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
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
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
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
Badary O, Al-Shabanah O, Nagi M et al (1998) Acute and subchronic toxicity of thymoquinone in mice. Drug Dev Res 44:56–61
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
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
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
Boyle P, Levin BE (eds) (2008) World cancer report. IARC. IARC Press, Lyon
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
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
Collins K, Mitchell JR (2002) Telomerase in the human organism. Oncogene 21(4):564–579
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
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
Di Cristofano A, Pandolfi PP (2000) The multiple roles of PTEN in tumor suppression. Cell 100:387–390
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
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
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
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
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
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
El-Sheikh AA, Morsy MA, Abdalla AM et al (2015) Mechanisms of thymoquinone hepatorenal protection in methotrexateinduced toxicity in rats. Mediat Inflamm 2015:859383
Fathy M, Nikaido T (2013) In vivo modulation of iNOS pathway in hepatocellular carcinoma by Nigella sativa. Environ Health Prev Med 18:377–385
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
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
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
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
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
Harari PM, Allen GW, Bonner JA (2007) Biology of interactions: antiepidermal growth factor receptor agents. J Clin Oncol 25:4057–4065
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
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
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
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
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
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
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
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
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
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
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
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
Normanno N, De Luca A, Bianco C et al (2006) Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366:2–16
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Salmena L, Carracedo A, Pandolfi PP et al (2008) Tenets of PTEN tumor suppression. Cell 133:403–414
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
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
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
Stewart BW, Wild CP (eds) (2014) Cancer etiology. World cancer report. World Health Organization. ISBN: 9283204298
Taketo MM (1998) Cyclooxygenase-2 inhibitors in tumorigenesis (part II). J Natl Cancer Inst 90:1609–1620
Taylor WR, Stark GR (2001) Regulation of the G2/M transition by p53. Oncogene 20:1803–1815
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
Thomson LL, Lawton FG, Knowles RG et al (1994) NO synthase activity in human gynecological cancer. Cancer Res 54:1352–1354
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
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
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
Waggoner SE (2003) Cervical cancer. Lancet 361(9376):2217–2225
Wang X, Jiang X (2008) PTEN: a default gate-keeping tumor suppressor with a versatile tail. Cell Res 18:807–816
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
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
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
Woo CC, Kumar AP, Sethi G et al (2012) Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 83(4):443–451
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
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
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
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
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
Zhang L, Bai Y, Yang Y (2016) Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB. Oncol Lett 12(4):2840–2845
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
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Singapore Pte Ltd.
About this chapter
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
DOI: https://doi.org/10.1007/978-981-10-8800-1_3
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-10-8799-8
Online ISBN: 978-981-10-8800-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)