Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Reverse Screening Bioinformatics Approach to Identify Potential Anti Breast Cancer Targets Using Thymoquinone from Neutraceuticals Black Cumin Oil

Author(s): Sumathi Sundaravadivelu*, Sonia K. Raj, Banupriya S. Kumar, Poornima Arumugamand and Padma P. Ragunathan

Volume 19, Issue 5, 2019

Page: [599 - 609] Pages: 11

DOI: 10.2174/1871520619666190124155359

Price: $65

Abstract

Background: Functional foods, neutraceuticals and natural antioxidants have established their potential roles in the protection of human health and diseases. Thymoquinone (TQ), the main bioactive component of Nigella sativa seeds (black cumin seeds), a plant derived neutraceutical was used by ancient Egyptians because of their ability to cure a variety of health conditions and used as a dietary food supplement. Owing to its multi targeting nature, TQ interferes with a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Additionally, TQ can specifically sensitize tumor cells towards conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells besides being cost effective and safe. TQ was found to play a protective role when given along with chemotherapeutic agents to normal cells.

Methods: In the present study, reverse in silico docking approach was used to search for potential molecular targets for cancer therapy. Various metastatic and apoptotic targets were docked with the target ligand. TQ was also tested for its anticancer activities for its ability to cause cell death, arrest cell cycle and ability to inhibit PARP gene expression.

Results: In silico docking studies showed that TQ effectively docked metastatic targets MMPs and other apoptotic and cell proliferation targets EGFR. They were able to bring about cell death mediated by apoptosis, cell cycle arrest in the late apoptotic stage and induce DNA damage too. TQ effectively down regulated PARP gene expression which can lead to enhanced cancer cell death.

Conclusion: Thymoquinone a neutraceutical can be employed as a new therapeutic agent to target triple negative breast cancer which is otherwise difficult to treat as there are no receptors on them. Can be employed along with standard chemotherapeutic drugs to treat breast cancer as a combinatorial therapy.

Keywords: Neutraceuticals, thymoquinone, cancer targets, PARP gene, chemotherapeutic drugs, black cumin oil.

« Previous Next »
Graphical Abstract

[1]
Reis, F.S.; Martins, A.; Vasconcelos, M.H. Functional foods based on extracts or compounds derived from mushrooms. Trends Food Sci. Technol., 2017, 66, 48-62.
[2]
Wu, K.; Ju, T.; Deng, Y.; Xi, J. Mechanochemical assisted extraction: A novel, efficient, eco-friendly technology. Trends Food Sci. Technol., 2017, 66, 166-175.
[3]
Ecevit, H.; Gunduz, N.; Bilgic, K.; Izmirli, M. Gögebakan, B. The effect of thymoquinone on BEAS-2B cell viability and TGF-β1 release. Adv. Mod. Oncol. Res., 2017, 3(1), 15-19.
[4]
Barkat, M.A.; Abul, H.; Ahmad, J.; Khan, M.A.; Beg, S.; Ahmad, F.J. Insights into the targeting potential of thymoquinone for therapeutic intervention against triple-negative breast cancer. Curr. Drug Targets, 2017, 18, 13-16.
[5]
Ruddarraju, R.R.; Murugulla, A.C.; Kotla, R.; Tirumalasetty, M.C.B.; Wudaayagiri, R.; Donthabakthuni, S.; Marojuc, R. Design, synthesis, anticancer activity and docking studies of theophylline containing 1, 2, 3-triazoles with variant amide derivatives. MedChemComm, 2017, 8, 176-183.
[6]
Ebrahimi, M. A short review on ferro fluids surface modification by natural and biocompatible polymers. Nanomed. J., 2016, 3, 155-158.
[7]
Dastjerdi, M.N.; Mehdiabady, E.M.; Iranpour, F.G.; Bahramian, H. Effect of thymoquinone on P53 gene expression and consequence apoptosis in breast cancer cell line. Int. J. Prev. Med., 2017, 7, 66-78.
[8]
Modi, S.; Hughes, M.; Garrow, A.; White, A. The value of in silico chemistry in the safety assessment of chemicals in the consumergoods and pharmaceutical industries. Drug Discov, 2011, 17, 135-142.
[9]
Krishan, A. Rapid flow cytofluorometric analysis of mammalian cell cycle bypropidium iodide staining. J. Cell Biol., 1975, 66, 188-193.
[10]
Tice, R.R.; Agurell, E.; Anderson, D.; Burlinson, B.; Hartmann, A.; Kobayashi, H.; Obayashi, H.; Miyamae, Y.; Rojas, E.; Ryu, J.C.; Sasaki, Y.F. Single cell gel/comet assay: Guidelines for in vitro and in vivo genetic toxicology testing. Environ. Mol. Mutagen., 2000, 35, 206-221.
[11]
Sridhar, A.; Saremy, S.; Bhattacharjee, B. Elucidation of molecular targets of bioactive principles of black cumin relevant to its anti - tumour functionality - an in silico target fishing approach. Bioinformation, 2014, 10, 684-688.
[12]
Rajput, B.N.S.; Kumar, P.; Dey, K.K.; Pal, I.; Parekh, A.; Mandal, M. Molecular targeting of Akt by thymoquinone promotes G1 arrest through translation inhibition of cyclin D1 and induces apoptosis in breast cancer cells. Life Sci., 2013, 93, 783-790.
[13]
Camargo, M.S.; Oliveira, M.T.; Santoni, M.M.; Resende, F.A.; Oliveira-Höhne, F.A.A.P.; Espanha, L.G.; Nogueira, C.H.; Cuesta-Rubio, O.; Vilegas, W.; Varanda, E.A. Effects of nemorosone, isolated from the plant Clusiarosea, on the cell cycle and gene expression in MCF-7 BUS breast cancer cell lines. Phytomedicine, 2015, 22, 153-157.
[14]
Abu, N.; Akhtar, M.N.; Ho, W.Y.; Yeap, S.K.; Alitheen, N.B. 3-Bromo-1-hydroxy, 10 anthraquinone (BHAQ) inhibits growth and migration of the human breast cancer cell lines MCF-7 and MDA-MB 231. Molecules, 2013, 18, 10367-10377.
[15]
Chen, C.; Wang, M.L.; Jin, C.; Chen, H.J.; Li, S.H.; Li, S.Y.; Dou, X.F.; Jia, J.Q.; Gui, Z.Z. Cordycepsmilitaris polysaccharide triggers apoptosis andG0/G1 cell arrest in cancer cells. J. Asia Pac. Entomol., 2015, 18, 433-438.
[16]
Xue, R.; Han, N.; Xia, M.; Ye, C.; Hao, Z.; Wang, L.; Wang, Y.; Yang, J.; Saiki, I.; Yin, J. TXA9, a cardiac glycoside from Streptocaulon juventas, exerts a potent anti-tumor activity against human non-small cell lung cancer cells in vitro and in vivo. Steroids, 2015, 94, 51-59.
[17]
Bohlooli, S.; Bohlooli, S.; Aslanian, S.R.; Nouria, F.; Teimourzadeh, A. Aqueous extract of Agrostemmagithago seed inhibits caspase 3 and induces cell cycle arrest at G1 phase in AGS cell line. J. Ethnopharmacol., 2015, 10, 1-5.
[18]
Longato, G.B.; Fiorito, G.F.; Vendramini-Costa, D.B.; Sousa, I.M.D.O.; Tinti, S.V.; Ruiz, A.L.T.G.; Almeida, S.M.V.D.; Padilha, R.J.R.; Foglio, M.A.; Carvalho, J.E.D. Different cell death responses induced byeupomatenoid-5 in MCF-7 and 786-0 tumor cell lines. Toxicol. In Vitro, 2015, 29, 1026-1033.
[19]
Tan, Y.S.; Ooi, K.K.; Ang, K.P.; Akim, A.M.; Cheah, Y.K.
Halim, S.N.A.; Seng, H.; Tiekink, E.R.T. Molecular mechanisms of apoptosis and cell selectivity of zinc dithio carbamates functionalized with hydroxyethyl substituents. Inorg. Biochem., 2015, 150, 48-62.
[20]
Jia, N.; Li, T.; Diao, X.; Kong, B. Protective effects of black currant (Ribesnigrum L.) extract on hydrogen peroxide-induced damage in lung fibroblast MRC-5 cells in relation to the antioxidant activity. J. Funct. Foods, 2014, 11, 142-151.
[21]
Jain, A.; Samykutty, A.; Jackson, C.; Browning, D.; Bollag, W.B.; Thangaraju, M.; Takahashi, S.; Singh, S.R. Curcumin inhibits PhIP induced cytotoxicity in breast epithelial cells through multiple molecular targets. Cancer Lett., 2015, 365, 122-131.
[22]
Moirangthem, D.S.; Laishram, S.; Borah, J.C.; Kalita, M.C.; Talukdar, N.C. Cephalotaxus griffithii Hook f. needle extract induces cell cycle arrest, apoptosis and suppression of hTERT and hTR expression on human breast cancer cells. BMC Complement. Altern. Med., 2014, 14, 305-315.
[23]
Liu, X.S.; Jiang, J.; Jiao, X.Y.; Wu, Y.; Lin, J-H.; Cai, Y.M. Lycorine induces apoptosis and down-regulation of Mcl-1 in human leukemia cells. Cancer Lett., 2009, 274, 16-24.
[24]
Zheng, Y.D.; Xu, X.Q.; Peng, F. The poly(ADP-ribose) polymerase-1inhibitor 3-aminobenzamide suppresses cell growth and migration, enhancing suppressive effects of cisplatin in osteosarcoma cells. Oncol. Rep., 2011, 25, 1399-1405.
[25]
Munoz-Gamez, J.A.; Quiles-Pérez, R.; Ruiz-Extremera, A. Inhibition of poly (ADP-ribose) polymerase-1 enhances doxorubicin activity against liver cancer cells. Cancer Lett., 2011, 301, 47-56.

Rights & Permissions Print Cite
Article Metrics
44
3
© 2024 Bentham Science Publishers | Privacy Policy