Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa)

Cancer is a life-threatening disease and a major leading cause of death worldwide. Drug resistance and adverse effects impede the success of chemotherapy. Hence, searching for anti-cancer bioactive compounds with low toxicity from natural products is now in demand. Thymoquinone (TQ), the bioac...

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Main Author:	Ng, Wei Keat
Format:	Thesis
Language:	English
Published:	2015
Subjects:	Cancer cells
Online Access:	http://psasir.upm.edu.my/id/eprint/71269/1/IB%202015%2037%20IR.pdf
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id	my-upm-ir.71269
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spelling	my-upm-ir.712692019-11-13T04:21:40Z Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa) 2015-07 Ng, Wei Keat Cancer is a life-threatening disease and a major leading cause of death worldwide. Drug resistance and adverse effects impede the success of chemotherapy. Hence, searching for anti-cancer bioactive compounds with low toxicity from natural products is now in demand. Thymoquinone (TQ), the bioactive compound of Nigella sativa, has been reported to exert anti-cancer properties. Nevertheless, TQ exhibits poor oral bioavailability. Therefore, nanostructured lipid carrier (NLC), provides an alternative delivery system for TQ to overcome the limitations. The objective of the study was to determine the cytotoxicity and mechanisms of action of TQ and TQ-NLC towards cervical cancer cells (SiHa and HeLa). The cytotoxicity of TQ towards SiHa and HeLa was determined by MTT assay. Cell cycle and mode of cell death was performed by using flowcytometry. The expression of p53, Bcl-2 and Bax, and caspases was studied by using Western blot and ELISA, respectively. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was synthesized by high pressure homogenization method. Physicochemical characteristics of TQ-NLC were determined. Cytotoxicity of TQNLC_ 4 towards SiHa and HeLa cells was evaluated by MTT assay. In vitro drug release kinetic, gastrointestinal digestion, absorption and bioavailability studies of TQ-NLC_4 were performed. Result shows that TQ was cytotoxic towards SiHa and HeLa cells by inducing cell cycle arrest and apoptosis in the cells. Elevation of Bax to Bcl-2 ratio and expression of caspase-3 and -9 were noted in SiHa cells while in HeLa cells, elevation of Bax to Bcl-2 ratio and expression of caspase-3, -8 and -9 were noted. Physicochemical analysis revealed that average diameter of TQ-NLC_4 was less than 100 nm. TQ-NLC_4 was found stable up to 24 months. High EE and DLC of TQ-NLC_4 were achieved. TQNLC_ 4 was cytotoxic towards SiHa and HeLa cells. TQ was released from NLC in a zero-order manner. Degradation and aggregation of TQ-NLC_4 occurred in simulated intestinal fluid. In vitro absorption and bioavailability studies indicated that bioavailabilty of TQ-NLC_4 was high. In conclusion, TQ was cytotoxic against the cervical cancer cells by modulating the apoptotic pathways. NLC conferred drug controlled release, protection and enhanced bioavailability to TQ. Hence, TQ-NLC_4 may be a promising anti-cancer agent against cervical cancer. Cancer cells Cytotoxicity, Cell-mediated 2015-07 Thesis http://psasir.upm.edu.my/id/eprint/71269/ http://psasir.upm.edu.my/id/eprint/71269/1/IB%202015%2037%20IR.pdf text en public doctoral Universiti Putra Malaysia Cancer cells Cytotoxicity, Cell-mediated
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
topic	Cancer cells Cancer cells
spellingShingle	Cancer cells Cancer cells Ng, Wei Keat Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa)
description	Cancer is a life-threatening disease and a major leading cause of death worldwide. Drug resistance and adverse effects impede the success of chemotherapy. Hence, searching for anti-cancer bioactive compounds with low toxicity from natural products is now in demand. Thymoquinone (TQ), the bioactive compound of Nigella sativa, has been reported to exert anti-cancer properties. Nevertheless, TQ exhibits poor oral bioavailability. Therefore, nanostructured lipid carrier (NLC), provides an alternative delivery system for TQ to overcome the limitations. The objective of the study was to determine the cytotoxicity and mechanisms of action of TQ and TQ-NLC towards cervical cancer cells (SiHa and HeLa). The cytotoxicity of TQ towards SiHa and HeLa was determined by MTT assay. Cell cycle and mode of cell death was performed by using flowcytometry. The expression of p53, Bcl-2 and Bax, and caspases was studied by using Western blot and ELISA, respectively. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was synthesized by high pressure homogenization method. Physicochemical characteristics of TQ-NLC were determined. Cytotoxicity of TQNLC_ 4 towards SiHa and HeLa cells was evaluated by MTT assay. In vitro drug release kinetic, gastrointestinal digestion, absorption and bioavailability studies of TQ-NLC_4 were performed. Result shows that TQ was cytotoxic towards SiHa and HeLa cells by inducing cell cycle arrest and apoptosis in the cells. Elevation of Bax to Bcl-2 ratio and expression of caspase-3 and -9 were noted in SiHa cells while in HeLa cells, elevation of Bax to Bcl-2 ratio and expression of caspase-3, -8 and -9 were noted. Physicochemical analysis revealed that average diameter of TQ-NLC_4 was less than 100 nm. TQ-NLC_4 was found stable up to 24 months. High EE and DLC of TQ-NLC_4 were achieved. TQNLC_ 4 was cytotoxic towards SiHa and HeLa cells. TQ was released from NLC in a zero-order manner. Degradation and aggregation of TQ-NLC_4 occurred in simulated intestinal fluid. In vitro absorption and bioavailability studies indicated that bioavailabilty of TQ-NLC_4 was high. In conclusion, TQ was cytotoxic against the cervical cancer cells by modulating the apoptotic pathways. NLC conferred drug controlled release, protection and enhanced bioavailability to TQ. Hence, TQ-NLC_4 may be a promising anti-cancer agent against cervical cancer.
format	Thesis
qualification_level	Doctorate
author	Ng, Wei Keat
author_facet	Ng, Wei Keat
author_sort	Ng, Wei Keat
title	Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa)
title_short	Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa)
title_full	Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa)
title_fullStr	Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa)
title_full_unstemmed	Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa)
title_sort	cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (siha and hela)
granting_institution	Universiti Putra Malaysia
publishDate	2015
url	http://psasir.upm.edu.my/id/eprint/71269/1/IB%202015%2037%20IR.pdf
_version_	1747812996671864832

Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa)

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