Ginger: A Novel Strategy to Battle Cancer through Modulating Cell Signalling Pathways: A Review

Author(s): Ahmad Almatroudi, Mohammed A. Alsahli, Faris Alrumaihi, Khaled S. Allemailem, Arshad H. Rahmani*.

Journal Name: Current Pharmaceutical Biotechnology

Volume 20 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Numerous studies have been performed in understanding the development of cancer. Though, the mechanism of action of genes in the development of cancer remains to be explained. The current mode of treatment of cancer shows adverse effects on normal cells and also alter the cell signalling pathways. However, ginger and its active compound have fascinated research based on animal model and laboratories during the past decade due to its potentiality in killing cancer cells. Ginger is a mixture of various compounds including gingerol, paradol, zingiberene and shogaol and such compounds are the main players in diseases management. Most of the health-promoting effects of ginger and its active compound can be attributed due to its antioxidant and anti-tumour activity. Besides, the active compound of ginger has proven its role in cancer management through its modulatory effect on tumour suppressor genes, cell cycle, apoptosis, transcription factors, angiogenesis and growth factor. In this review, the role of ginger and its active compound in the inhibition of cancer growth through modulating cell signalling pathways will be reviewed and discussed.

Keywords: Ginger, shogaol, gingerol, antitumor activity, antioxidant activity, cell signalling pathway.

[1]
Surh, Y.J. Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat. Res., 1999, 428(1-2), 305-327.
[2]
Grzanna, R.; Lindmark, L.; Frondoza, C.G. Ginger-an herbal medicinal product with broad anti-inflammatory actions. J. Med. Food, 2005, 8, 125-132.
[3]
Altman, R.D.; Marcussen, K.C. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum., 2001, 44, 11- 2531-2538.
[4]
Ling, H.; Yang, H.; Tan, S.H.; Chui, W.K.; Chew, E.H. 6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-kappa B activation. Br. J. Pharmacol., 2010, 161, 1763-1777.
[5]
Tan, B.S.; Kang, O.; Mai, C.W.; Tiong, K.H.; Khoo, A.S.; Pichika, M.R.; Bradshaw, T.D.; Leong, C.O. 6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor gamma (PPAR gamma). Cancer Lett., 2013, 336, 127-139.
[6]
Lee, H.S.; Seo, E.Y.; Kang, N.E.; Kim, W.K. [6]-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells. J. Nutr. Biochem., 2008, 19, 313-319.
[7]
Jeong, C.H.; Bode, A.M.; Pugliese, A.; Cho, Y.Y.; Kim, H.G.; Shim, J.H. [6] gingerol suppresses colon cancer growth by targeting leukotriene a4 hydrolase. Cancer Res., 2009, 69, 5584-5591.
[8]
Liu, Y.; Whelan, R.J.; Pattnaik, B.R.; Ludwig, K.; Subudhi, E.; Rowland, H.; Claussen, N.; Zucker, N.; Uppal, S.; Kushner, D.M.; Felder, M.; Patankar, M.S.; Kapur, A. Terpenoids from Zingiber officinale (Ginger) induce apoptosis in endometrial cancer cells through the activation of p53. PLoS One, 2012, 7(12), e53178.
[9]
Saha, A.; Blando, J.; Silver, E.; Beltran, L.; Sessler, J.; DiGiovanni, J. 6-Shogaol from dried ginger inhibits growth of prostate cancer cells both in vitro and in vivo through inhibition of STAT3 and NF-kappa B signaling. Cancer Prev. Res., 2014, 7, 627-638.
[10]
Tuntiwechapikul, W.; Taka, T.; Songsomboon, C.; Kaewtunjai, N.; Imsumran, A.; Makonkawkeyoon, L.; Pompimon, W.; Lee, T.R. Ginger extract inhibits human telomerase reverse transcriptase and c-Myc expression in A549 lung cancer cells. J. Med. Food, 2010, 13, 1347-1354.
[11]
Abdullah, S.; Abidin, S.A.Z.; Murad, N.A.; Makpol, S.; Ngah, W.Z.W.; Yusof, Y.A.M. Ginger extract (Zingiber officinale) triggers apoptosis and G0/G1 cells arrest in HCT 116 and HT 29 colon cancer cell lines. Afr. J. Biochem. Res., 2010, 4, 134-142.
[12]
Johnstone, R.W.; Ruefli, A.A.; Lowe, S.W. Apoptosis: A link between cancer genetics and chemotherapy. Cell, 2002, 108, 153-164.
[13]
Elkady, A.I.; Osama, A.A.; Baeshen, N.A.; Rahmy, T.R. Differential Control of Growth, Apoptotic activity, and gene expression in human breast cancer cells by extracts derived from medicinal herbs Zingiber officinale. J. Biomed. Biotechnol., 2012, 2012, 6143.
[14]
Folkman, J. Tumor angiogenesis: Therapeutic implications. N. Engl. J. Med., 1971, 285(21), 1182-1186.
[15]
Ferrara, N.; Kerbel, R.S. Angiogenesis as a therapeutic target. Nature, 2005, 438(7070), 967-974.
[16]
Folkman, J. Fighting cancer by attacking its blood supply. Sci. Am., 1996, 275(3), 150-154.
[17]
Kim, S.O.; Chun, K.S.; Kundu, J.K.; Surh, Y.J. Inhibitory effects of [6]-gingerol on PMA-induced COX-2 expression and activation of NF-kappa B and p38 MAPK in mouse skin. Biofactors, 2004, 21(1-4), 27-31.
[18]
Rhode, J.; Fogoros, S.; Zick, S.; Wahl, H.; Griffith, K.A.; Huang, J.; Liu, J.R. Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells. BMC Complement. Altern. Med., 2007, 20(7), 44.
[19]
Weng, C.J.; Wu, C.F.; Huang, H.W.; Ho, C.T.; Yen, G.C. Anti-invasion effects of 6-shogaol and 6-gingerol, two active components in ginger, on human hepatocarcinoma cells. Mol. Nutr. Food Res., 2010, 54(11), 1618-1627.
[20]
Rahmani, A.H.; Al Shabrmi, F.M.; Allemailem, K.S.; Aly, S.M.; Khan, M.A. Implications of green tea and its constituents in the prevention of cancer via the modulation of cell signalling pathway. BioMed Res. Int., 2015, 2015, Article ID 925640.
[21]
Rahmani, A.H.; Aly, S.M.; Babiker, A.Y.; Srikar, S.; Khan, A.A. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, antioxidant and anti-tumour activity. Int. J. Clin. Exp. Med., 2014, 7, 483-491.
[22]
Rahmani, A.H.; Al Zohairy, M.A.; Aly, S.M.; Khan, M.A. Curcumin: A potential candidate in prevention of cancer via modulation of molecular pathways. BioMed Res. Int., 2014, 2014, 761608.
[23]
Kikuzaki, H.; Nakatani, N. Cyclic diarylheptanoids from rhizomes of Zingiber officinale. Phytochemistry, 1996, 43, 273-277.
[24]
Danwilai, K.; Konmun, J.; Sripanidkulchai, B.; Subongkot, S. Antioxidant activity of ginger extract as a daily supplement in cancer patients receiving adjuvant chemotherapy: A pilot study. Cancer Manag. Res., 2017, 9, 11-18.
[25]
Bo, M.; Li, H.; Qu, W.; Yuan, H. anticancer effects of gingerol in retinoblastoma cancer cells (RB355 cell line) are mediated via apoptosis induction, cell cycle arrest and upregulation of PI3K/Akt signaling pathway. Med. Sci. Monit., 2018, 24, 1980-1987.
[26]
Rastogi, N.; Duggal, S.; Singh, S.K.; Porwal, K.; Srivastava, V.K.; Maurya, R.; Bhatt, M.L.; Mishra, D.P. Proteasome inhibition mediates p53 reactivation and anti-cancer activity of 6-gingerol in cervical cancer cells. Oncotarget, 2015, 6(41), 43310-43325.
[27]
Hsu, Y.L.; Chen, C.Y.; Lin, I.P.; Tsai, E.M.; Kuo, P.L.; Hou, M.F. 4-Shogaol, an active constituent of dietary ginger, inhibits metastasis of MDA-MB-231 human breast adenocarcinoma cells by decreasing the repression of NF-kappaB/Snail on RKIP. J. Agric. Food Chem., 2012, 60, 852-861.
[28]
Rahmani, A.H.; Alzohairy, M.A.; Khan, M.A.; Aly, S.M. Therapeutic implications of black seed and its constituent thymoquinone in the prevention of cancer through inactivation and activation of molecular pathways. Evid. Based Complement. Alternat. Med., 2014, 2014, 724658.
[29]
Pashaei-Asl, R.; Pashaei-Asl, F.; Gharabaghi, P.M.; Khodadadi, K.; Ebrahimi, M.; Ebrahimie, E.; Pashaiasl, M. The inhibitory effect of ginger extract on Ovarian cancer cell line; application of systems biology. Adv. Pharm. Bull., 2017, 7, 241-249.
[30]
Zhang, S.; Liu, Q.; Liu, Y.; Qiao, H. Zerumbone, a Southeast Asian ginger sesquiterpene, induced apoptosis of pancreatic carcinoma cells through p53 signaling pathway. Evid. Based Complement. Alternat. Med., 2012, 2012, 8.
[31]
Hollowood, K.; Macartney, J.C. Reduced apoptotic cell death in follicular lymphoma. J. Pathol., 1991, 163(4), 337-342.
[32]
Green, D.R. Apoptotic pathways: Paper wraps stone blunts scissors. Cell, 2000, 102(1), 1-4.
[33]
Annamalai, G.; Kathiresan, S.; Kannappan, N. [6]-Shogaol, a dietary phenolic compound, induces oxidative stress mediated mitochondrial dependent apoptosis through activation of proapoptotic factors in Hep-2 cells. Biomed. Pharmacother., 2016, 82, 226-236.
[34]
Wang, C.C.; Chen, L.G.; Lee, L.T.; Yang, L.L. Effects of 6-gingerol, an antioxidant from ginger, on inducing apoptosis in human leukemic HL-60 cells. In Vivo, 2003, 17(6), 641-645.
[35]
Lee, S.H.; Cekanova, M.B. Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells. Mol. Carcinog., 2008, 47, 197-208.
[36]
Nigam, N.; George, J.; Srivastava, S.; Roy, P.; Bhui, K.; Singh, M.; Shukla, Y. Induction of apoptosis by [6]-gingerol associated with the modulation of p53 and involvement of mitochondrial signaling pathway in B[a]P-induced mouse skin tumorigenesis. Cancer Chemother. Pharmacol., 2010, 65(4), 687-696.
[37]
Ryu, M.J.; Chung, H.S. [10]-Gingerol induces mitochondrial apoptosis through activation of MAPK pathway in HCT116 human colon cancer cells. In Vitro Cell. Dev. Biol. Anim., 2015, 51, 92-101.
[38]
Luo, Y.; Chen, X.; Luo, L.; Zhang, Q.; Gao, C.; Zhuang, X.; Yuan, S.; Qiao, T. [6]-Gingerol enhances the radiosensitivity of gastric cancer via G2/M phase arrest and apoptosis induction. Oncol. Rep., 2018, 39(5), 2252-2260.
[39]
Lee, S.H.; Cekanova, M.; Baek, S.J. Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells. Mol. Carcinog., 2008, 47, 197-208.
[40]
Liu, Q.; Peng, Y-B.; Zhou, P.; Qi, L-W.; Zhang, M.; Gao, N.; Liu, E.H.; Li, P. 6-Shogaol induces apoptosis in human leukemia cells through a process involving caspase-mediated cleavage of eIF2α. Mol. Cancer, 2013, 12(1), 135.
[41]
Hsu, Y.L.; Chen, C.Y.; Hou, M.F.; Tsai, E.M.; Jong, Y.J.; Hung, C.H.; Kuo, P.L. 6-Dehydrogingerdione, an active constituent of dietary ginger, induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human breast cancer cells. Mol. Nutr. Food Res., 2010, 54, 1307-1317.
[42]
Chang, K.W.; Kuo, C.Y. 6-Gingerol modulates proinflammatory responses in dextran sodium sulfate (DSS)-treated Caco-2 cells and experimental colitis in mice through adenosine monophosphate-activated protein kinase (AMPK) activation. Food Funct., 2015, 6(10), 3334-3341.
[43]
Fan, J.; Yang, X.; Bi, Z. 6-Gingerol inhibits osteosarcoma cell proliferation through apoptosis and AMPK activation. Tumour Biol., 2015, 36(2), 1135-1141.
[44]
Radhakrishnan, E.K.; Bava, S.V.; Narayanan, S.S.; Nath, L.R.; Thulasidasan, A.K.; Soniya, E.V.; Anto, R.J. [6]-Gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in colon cancer cells by inhibiting MAPK/AP-1 signaling. PLoS One, 2014, 9, e104401.
[45]
Li, Y.; Tran, V.H.; Koolaji, N.; Duke, C.; Roufogalis, B.D. (S)-[6]-Gingerol enhances glucose uptake in L6 myotubes by activation of AMPK in response to [Ca2+].. J. Pharm. Pharm. Sci., 2013, 16, 304-312.
[46]
Hashem, R.M.; Rashed, L.A.; Hassanin, K.M.A.; Hetta, M.H.; Ahmed, A.O. Effect of 6-gingerol on AMPK- NF-κB axis in high fat diet fed rats. Biomed. Pharmacother., 2017, 88, 293-301.
[47]
Li, Y.; Xu, B.; Xu, M.; Chen, D.; Xiong, Y.; Lian, M.; Sun, Y.; Tang, Z.; Wang, L.; Jiang, C.; Lin, Y. 6-Gingerol protects intestinal barrier from ischemia/reperfusion-induced damage via inhibition of p38 MAPK to NF-κB signalling. Pharmacol. Res., 2017, 119, 137-148.
[48]
Weng, C.J.; Chou, C.P.; Ho, C.T.; Yen, G.C. Molecular mechanism inhibiting human hepatocarcinoma cell invasion by 6-shogaol and 6-gingerol. Mol. Nutr. Food Res., 2012, 56(8), 1304-1314.
[49]
Kim, S.O.; Kundu, J.K.; Shin, Y.K.; Park, J.H.; Cho, M.H.; Kim, T.Y.; Surh, Y.J. [6]-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-κB in phorbol ester-stimulated mouse skin. Oncogene, 2005, 24, 2558-2567.
[50]
Witsch, E.; Sela, M.; Yarden, Y. Roles for growth factors in cancer progression. Physiology (Bethesda), 2010, 25, 85-101.
[51]
Kim, E.C.; Min, J.K.; Kim, T.Y.; Lee, S.J.; Yang, H.O.; Han, S.; Kim, Y.M.; Kwon, Y.G. [6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo. Biochem. Biophys. Res. Commun., 2005, 335(2), 300-308.
[52]
Hou, C.; Miao, Y.; Ji, H.; Wang, S.; Liang, G.; Zhang, Z.; Hong, W. 6-Gingerol inhibits hair cycle via induction of MMP2 and MMP9 expression. An. Acad. Bras. Cienc., 2017, 89, 2707-2717.
[53]
Wang, D.; Jiang, Y.; Yang, X.; Wei, Q.; Wang, H. 6-Shogaol reduces progression of experimental endometriosis in vivo and in vitro via regulation of VGEF and inhibition of COX-2 and PGE2-mediated inflammatory responses. Korean J. Physiol. Pharmacol., 2018, 22(6), 627-636.
[54]
Normanno, N.; de Luca, A.; Bianco, C.; Strizzi, L.; Mancino, M.; Maiello, M.R.; Carotenuto, A.; De Feo, G.; Caponigro, F.; Salomon, D.S. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene, 2006, 366, 2-16.
[55]
Bode, A.M.; Ma, W.Y.; Surh, Y.J.; Dong, Z. Inhibition of epidermal growth factor-induced cell transformation and activator protein 1 activation by [6]-gingerol. Cancer Res., 2001, 61(3), 850-853.
[56]
Geng, S.; Zheng, Y.; Meng, M. Gingerol reverses the cancer-promoting effect of capsaicin by increased TRPV1 level in a urethane-induced lung carcinogenic model. J. Agric. Food Chem., 2016, 64, 6203-6211.
[57]
Park, S.A.; Park, I.H.; Cho, J.S.; Moon, Y.M.; Lee, S.H.; Kim, T.H.; Lee, S.H.; Lee, H.M. Effect of [6]-gingerol on myofibroblast differentiation in transforming growth factor beta 1-induced nasal polyp-derived fibroblasts. Am. J. Rhinol. Allergy, 2012, 26(2), 97-103.
[58]
Kim, M.O.; Lee, M.H.; Oi, N.; Kim, S.H.; Bae, K.B.; Huang, Z.; Kim, D.J.; Reddy, K.; Lee, S.Y.; Park, S.J.; Kim, J.Y.; Xie, H.; Kundu, J.K.; Ryoo, Z.Y.; Bode, A.M.; Surh, Y.J.; Dong, Z. [6]-Shogaol inhibits growth and induces apoptosis of non-small cell lung cancer cells by directly regulating Akt1/2. Carcinogenesis, 2014, 35, 683-691.
[59]
Karin, M.; Cao, Y.; Greten, F.R.; Li, Z.W. NF-kappa B in cancer: from innocent bystander to major culprit. Nat. Rev. Cancer, 2002, 2(4), 301-310.
[60]
Ling, H.; Yang, H.; Tan, S.H.; Chui, W.K.; Chew, E.H. 6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation. Br. J. Pharm, 2010, 161, 1763-1777.
[61]
Kim, S.O.; Kim, M.R. [6]-Gingerol Prevents disassembly of cell junctions and activities of mmps in invasive human pancreas cancer cells through ERK/NF- kappa B/snail signal transduction pathway. Evid. Based Complement. Alternat. Med., 2013, 2013, 761852.
[62]
Zhou, L.; Qi, L.; Jiang, L.; Zhou, P.; Ma, J.; Xu, X.; Li, P. Antitumor activity of gemcitabine can be potentiated in pancreatic cancer through modulation of TLR4/NF-κB signalling by 6-shogaol. AAPS J., 2014, 16(2), 246-257.
[63]
Kim, S.M.; Kim, C.; Bae, H.; Lee, J.H.; Baek, S.H.; Nam, D.; Chung, W.S.; Shim, B.S.; Lee, S.G.; Kim, S.H.; Sethi, G.; Ahn, K.S. 6-Shogaol exerts anti-proliferative and pro-apoptotic effects through the modulation of STAT3 and MAPKs signaling pathways. Mol. Carcinog., 2015, 54(10), 1132-1146.
[64]
Luettig, J.; Rosenthal, R.; Lee, I.M.; Krug, S.M.; Schulzke, J.D. The ginger component 6-shogaol prevents TNF-alpha-induced barrier loss via inhibition of PI3K/Akt and NF-kappa B signaling. Mol. Nutr. Food Res., 2016, 60, 2576-2586.
[65]
Wang, Y.; Wang, S.; Song, R.; Cai, J.; Xu, J.; Tang, X.; Li, N. Ginger polysaccharides induced cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Int. J. Biol. Macromol., 2018, 123, 81-90.
[66]
Park, Y.J.; Wen, J.; Bang, S.; Park, S.W.; Song, S.Y. [6]-Gingerol induces cell cycle arrest and cell death of mutant p53-expressing pancreatic cancer cells. Yonsei Med. J., 2006, 47, 688-697.
[67]
Wu, J.J.; Omar, H.A.; Lee, Y.R.; Teng, Y.N.; Chen, P.S.; Chen, Y.C.; Huang, H.S.; Lee, K.H. Hung, J.H. 6-Shogaol induces cell cycle arrest and apoptosis in human hepatoma cells through pleiotropic mechanisms. Eur. J. Pharmacol., 2015, 762, 449-458.
[68]
Liu, Q.; Peng, Y.B.; Qi, L.W.; Cheng, X.L.; Xu, X.J.; Liu, L.L.; Liu, E.H.; Li, P. The cytotoxicity mechanism of 6-shogaol-treated HeLa human cervical cancer cells revealed by label-free shotgun proteomics and bioinformatics analysis. Evid. Based Complement. Alternat. Med., 2012, 2012, 278652.
[69]
Gan, F.F.; Nagle, A.A.; Ang, X.; Ho, O.H.; Tan, S.H.; Yang, H.; Chui, W.K.; Chew, E.H. Shogaols at proapoptotic concentrations induce G(2)/M arrest and aberrant mitotic cell death associated with tubulin aggregation. Apoptosis, 2011, 16, 856-867.
[70]
Mangelsdorf, D.J.; Thummel, C.; Beato, M.; Herrlich, P.; Schütz, G.; Umesono, K.; Blumberg, B.; Kastner, P.; Mark, M.; Chambon, P.; Evans, R.M. The nuclear receptor super-family: The second decade. Cell, 1995, 83, 835-839.
[71]
Sarraf, P.; Mueller, E.; Jones, D.; King, F.J.; DeAngelo, D.J.; Partridge, J.B.; Holden, S.A.; Chen, L.B.; Singer, S.; Fletcher, C.; Spiegelman, B.M. Differentiation and reversal of malignant changes in colon cancer through PPAR gamma. Nat. Med., 1998, 4, 1046-1052.
[72]
Kubota, T.; Koshizuka, K.; Williamson, E.A.; Asou, H.; Said, J.W.; Holden, S.; Miyoshi, I.; Koeffler, H.P. Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res., 1998, 58, 3344-3352.
[73]
Takahashi, N.; Okumura, T.; Motomura, W.; Fujimoto, Y.; Kawabata, I.; Kohgo, Y. Activation of PPAR gamma inhibits cell growth and induces apoptosis in human gastric cancer cells. FEBS Lett., 1999, 455, 135-139.
[74]
Tan, B.S.; Kang, O.; Mai, C.W.; Tiong, K.H.; Khoo, A.S.; Pichika, M.R.; Bradshaw, T.D.; Leong, C.O. 6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor γ (PPARγ). Cancer Lett., 2013, 336(1), 127-139.
[75]
Ranganathan, P.; Weaver, K.L.; Capobianco, A.J. Notch signalling in solid tumours: A little bit of everything but not all the time. Nat. Rev. Cancer, 2011, 11(5), 338-351.
[76]
Ray, A.; Vasudevan, S.; Sengupta, S. 6-shogaol inhibits breast cancer cells and stem cell-like spheroids by modulation of notch signaling pathway and induction of autophagic cell death. PLoS One, 2015, 10, e0137614.
[77]
Zvereva, M.I.; Shcherbakova, D.M.; Dontsova, O.A. Telomerase: structure, functions, and activity regulation. Biochemistry (Mosc.), 2010, 75, 1563-1583.
[78]
Tuntiwechapikul, W.; Taka, T.; Songsomboon, C.; Kaewtunjai, N.; Imsumran, A.; Makonkawkeyoon, L.; Pompimon, W.; Lee, T.R. Ginger extract inhibits human telomerase reverse transcriptase and c-Myc expression in A549 lung cancer cells. J. Med. Food, 2010, 13(6), 1347-1354.
[79]
Chandrasekharan, N.V.; Simmons, D.L. The cyclooxygenases. Genome Biol., 2004, 5(9), 2004.
[80]
Zha, S.; Yegnasubramanian, V. Nelson. W.G.; Isaacs, W.B.; De Marzo, A.M. Cyclooxygenases in cancer: Progress and perspective. Cancer Lett., 2004, 215, 1-20.
[81]
harma, S.; Stolina, M.; Yang, S.C.; Baratelli, F.; Lin, J.F.; Atianzar, K, Luo, J.; Zhu, L.; Lin, Y.; Huang, M.; Dohadwala, M.; Batra, R.K.; Dubinett, S.M. Tumor cyclooxygenase 2-dependent suppression of dendritic cell function. Clin. Cancer Res., 2003, 9, 961-968.
[82]
Jiang, Y.; Turgeon, D.K.; Wright, B.D.; Sidahmed, E.; Ruffin, M.T.; Brenner, D.E.; Sen, A.; Zick, S.M. Effect of ginger root on cyclooxygenase-1 and 15-hydroxyprostaglandin dehydrogenase expression in colonic mucosa of humans at normal and increased risk for colorectal cancer. Eur. J. Cancer Prev., 2013, 22, 455-460.
[83]
Kumar, A.; Rajendran, V.; Sethumadhavan, R.; Purohit, R. AKT kinase pathway: A leading target in cancer research. Scientif. World J., 2013, 2013, 756134.
[84]
Yu, Z.; Wan, Y.; Liu, Y.; Yang, J.; Li, L.; Zhang, W. Curcumin induced apoptosis via PI3K/Akt-signalling pathways in SKOV3 cells. Pharm. Biol., 2016, 54(10), 2026-2032.
[85]
Tahir, A.A.; Sani, N.F.; Murad, N.A.; Makpol, S.; Ngah, W.Z.; Yusof, Y.A. Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells. Nutr. J., 2015, 1(14), 31.
[86]
Fridman, R.; Toth, M.; Pena, D.; Mobashery, S. Activation of progelatinase B (MMP-9) by gelatinase A (MMP-2). Cancer Res., 1995, 55, 2548-2555.
[87]
Ling, H.; Yang, H.; Tan, S.H.; Chui, W.K.; Chew, E.H. 6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation. Br. J. Pharmacol., 2010, 161(8), 1763-1777.
[88]
McFadyen, M.C.; Melvin, W.T.; Murray, G.I. Cytochrome P450 enzymes: Novel options for cancer therapeutics. Mol. Cancer Ther., 2004, 3, 363-371.
[89]
Li, M.; Chen, P.Z.; Yue, Q.X.; Li, J.Q.; Chu, R.A.; Zhang, W.; Wang, H. Pungent ginger components modulates human cytochrome P450 enzymes in vitro. Acta Pharmacol. Sin., 2013, 34(9), 1237-1242.
[90]
Yao, J.; Ge, C.; Duan, D.; Zhang, B.; Cui, X.; Peng, S.; Liu, Y.; Fang, J. Activation of the phase II enzymes for neuroprotection by ginger active constituent 6-dehydrogingerdione in PC12 cells. J. Agric. Food Chem., 2014, 62(24), 5507-5518.
[91]
Shaikh, J.; Ankola, D.; Beniwal, D.V.; Singh, D.; Kumar, M.N. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur. J. Pharm. Sci., 2009, 37, 223-230.
[92]
Zhang, M.; Xu, C.; Liu, D.; Han, M.K.; Wang, L.; Merlin, D. Oral delivery of nanoparticles loaded with ginger active compound, 6-shogaol, attenuates ulcerative colitis and promotes wound healing in a murine model of ulcerative colitis. J. Crohn’s Colitis, 2017, 12(2), 217-229.
[93]
Zhang, M.Z.; Xiao, B.; Wang, H.; Han, M.K.; Zhang, Z.; Viennois, E.; Xu, C.L.; Merlin, D. Edible ginger-derived nano-lipids loaded with doxorubicin as a novel drug-delivery approach for colon cancer therapy. Mol. Ther., 2016, 24, 1783-1796.
[94]
Ryan, J.L.; Heckler, C.E.; Roscoe, J.A.; Dakhil, S.R.; Kirshner, J.; Flynn, P.J.; Hickok, J.T.; Morrow, G.R. Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: A URCC CCOP study of 576 patients. Support. Care Cancer, 2011, 20, 1479-1489.
[95]
Wu, H.; Ye, D.; Bai, Y.; Zhao, Y. Effect of dry ginger and roasted ginger on experimental gastric ulcers in rats. Zhongguo Zhongyao Zazhi, 1990, 15(5), 278-280, 317-318.
[96]
Weidner, M.S.; Sigwart, K. The safety of a ginger extract in the rat. J. Ethnopharmacol., 2000, 73, 513-520.
[97]
Weidner, M.S.; Sigwart, K. Investigation of the teratogenic potential of a Zingiber officinale extract in the rat. Reprod. Toxicol., 2001, 15, 75-80.
[98]
Jeena, K.; Liju, V.B.; Kuttan, R. A preliminary 13-week oral toxicity study of ginger oil in male and female Wistar rats. Int. J. Toxicol., 2011, 30(6), 662-670.
[99]
Kapoor, V.; Aggarwal, S.; Das, S.N. 6-Gingerol Mediates its anti tumor activities in human oral and cervical cancer cell lines through apoptosis and cell cycle arrest. Phytother. Res., 2016, 30(4), 588-595.
[100]
Zhang, F.; Thakur, K.; Hu, F.; Zhang, J.G.; Wei, Z.J. 10-Gingerol, a Phytochemical Derivative from “Tongling White Ginger”, inhibits cervical cancer: Insights into the molecular mechanism and inhibitory targets. J. Agric. Food Chem., 2017, 65, 2089-2099.
[101]
Zhang, F.; Thakur, K.; Hu, F.; Zhang, J.G.; Wei, Z.J. 10-Gingerol, a phytochemical derivative from “Tongling White Ginger”, inhibits cervical cancer: insights into the molecular mechanism and inhibitory targets. J. Agric. Food Chem., 2017, 65, 2089-2099.
[102]
Rhode, J.M.; Huang, J.; Fogoros, S.; Tan, L.; Zick, S.; Liu, J.R. Ginger induces apoptosis and autophagocytosis in ovarian cancer cells. Presented at the 97th AACR Annual Meeting, April 1-5, 2006. Washington, DC
[103]
Martin, A.C.B.M.; Fuzer, A.M.; Becceneri, A.B.; da Silva, J.A.; Tomasin, R.; Denoyer, D.; Kim, S.H.; McIntyre, K.A.; Pearson, H.B.; Yeo, B.; Nagpal, A.; Ling, X.; Selistre-de-Araújo, H.S.; Vieira, P.C.; Cominetti, M.R.; Pouliot, N. [10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo. Oncotarget, 2017, 8(42), 72260-72271.
[104]
Lee, H.S.; Seo, E.Y.; Kang, N.E.; Kim, W.K. [6]-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells. J. Nutr. Biochem., 2008, 19, 313-319.
[105]
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, 370-376.
[106]
Joo, J.H.; Hong, S.S.; Cho, Y.R.; Seo, D.W. 10-Gingerol inhibits proliferation and invasion of MDA-MB-231 breast cancer cells through suppression of Akt and p38MAPK activity. Oncol. Rep., 2016, 35, 779-784.
[107]
Hessien, M.; El-Gendy, S.; Donia, T.; Sikkena, M.A. Growth inhibition of human non-small lung cancer cells h460 by green tea and ginger polyphenols. Anticancer. Agents Med. Chem., 2012, 12(4), 383-390.
[108]
Liu, C.M.; Kao, C.L.; Tseng, Y.T.; Lo, Y.C.; Chen, C.Y. Ginger phytochemicals inhibit cell growth and modulate drug resistance factors in docetaxel resistant prostate cancer cell. Molecules, 2017, 22, 1477.
[109]
Habib, S.H.; Makpol, S.; Abdul Hamid, N.A.; Das, S.; Ngah, W.Z.; Yusof, Y.A. Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats. Clinics (São Paulo), 2008, 63, 807-813.
[110]
Al-Abbasi, F.A.; Alghamdi, E.A.; Baghdadi, M.A.; Alamoudi, A.J.; El-Halawany, A.M.; El-Bassossy, H.M.; Aseeri, A.H.; Al-Abd, A.M. Gingerol synergizes the cytotoxic effects of doxorubicin against liver cancer cells and protects from its vascular toxicity. Molecules, 2016, 21(7), E886.
[111]
Park, Y.J.; Wen, J.; Bang, S.; Park, S.W.; Song, S.Y. [6]-Gingerol induces cell cycle arrest and cell death of mutant p53-expressing pancreatic cancer cells. Yonsei Med. J., 2006, 47, 688-697.
[112]
Zhou, L.; Qi, L.; Jiang, L.; Zhou, P.; Ma, J.; Xu, X.; Li, P. Antitumor activity of gemcitabine can be potentiated in pancreatic cancer through modulation of TLR4/NF-κB signaling by 6-shogaol. AAPS J., 2014, 16(2), 246-257.
[113]
Huang, H.C.; Chiu, S.H.; Chang, T.M. Inhibitory effect of [6]-gingerol on melanogenesis in B16F10 melanoma cells and a possible mechanism of action. Biosci. Biotechnol. Biochem., 2011, 75(6), 1067-1072.
[114]
Lin, C.B.; Lin, C.C.; Tsay, G.J. 6-Gingerol inhibits growth of colon cancer cell lovo via induction of G2/M arrest. Evid. Based Complement. Alternat. Med., 2012, 326096.
[115]
Zeng, H.L.; Han, X.A.; Gu, C.; Zhu, H.Y.; Huang, X.S.; Gu, J.Q.; Zhong, Q.; Liu, G.J.; Ming, W.J.; Cai, X.N. Reactive oxygen species and mitochondrial membrane potential changes in leukemia cells during 6-gingerol induced apoptosis. Zhong Yao Cai, 2010, 33(4), 584-587.
[116]
Rastogi, N.; Gara, R.K.; Trivedi, R.; Singh, A.; Dixit, P.; Maurya, R.; Duggal, S.; Bhatt, M.L.; Singh, S.; Mishra, D.P. (6)-Gingerolinduced myeloid leukemia cell death is initiated by reactive oxygen species and activation of miR-27b expression. Free Radic. Biol. Med., 2014, 68, 288-301.
[117]
Fan, J.; Yang, X.; Bi, Z. 6-Gingerol inhibits osteosarcoma cell proliferation through apoptosis and AMPK activation. Tumour Biol., 2015, 36(2), 1135-1141.
[118]
Khater, D.S. The influence of ginger as a chemopreventive agent on proliferation and apoptosis in chemically induced oral carcinogenesis. Nat. Sci., 2010, 8, 44-51.
[119]
Lee, D.H.; Kim, D.W.; Jung, C.H.; Lee, Y.J.; Park, D. Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells. Toxicol. Appl. Pharmacol., 2014, 279(3), 253-265.


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VOLUME: 20
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Year: 2019
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DOI: 10.2174/1389201020666190119142331
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