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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| Format: | Thesis |
| Language: | English |
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2015
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| Online Access: | http://psasir.upm.edu.my/id/eprint/71269/ http://psasir.upm.edu.my/id/eprint/71269/1/IB%202015%2037%20IR%2816%29edited.pdf |
| _version_ | 1848867668985118720 |
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| author | Ng, Wei Keat |
| author_facet | Ng, Wei Keat |
| author_sort | Ng, Wei Keat |
| building | UPM Institutional Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-15T11:49:27Z |
| format | Thesis |
| id | upm-71269 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:40:10Z |
| publishDate | 2015 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-712692025-08-06T07:22:39Z http://psasir.upm.edu.my/id/eprint/71269/ Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa) 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. 2015-07 Thesis NonPeerReviewed text en http://psasir.upm.edu.my/id/eprint/71269/1/IB%202015%2037%20IR%2816%29edited.pdf Ng, Wei Keat (2015) Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa). Doctoral thesis, Universiti Putra Malaysia. http://ethesis.upm.edu.my/id/eprint/12531/ Cancer cells Cytotoxicity, Cell-mediated |
| spellingShingle | Cancer cells Cytotoxicity, Cell-mediated Ng, Wei Keat Cytotoxicity of thymoquinone and thymoquinone-loaded nanostrustured lipid carrier on cervical cancer cells (SiHa and HeLa) |
| title | 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_short | 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) |
| topic | Cancer cells Cytotoxicity, Cell-mediated |
| url | http://psasir.upm.edu.my/id/eprint/71269/ http://psasir.upm.edu.my/id/eprint/71269/ http://psasir.upm.edu.my/id/eprint/71269/1/IB%202015%2037%20IR%2816%29edited.pdf |