dc.contributor.author	Baba, Sayang
dc.date.accessioned	2023-07-18T07:27:06Z
dc.date.available	2023-07-18T07:27:06Z
dc.date.issued	2020
dc.description	Thesis (PhD. (Chemistry))
dc.description.abstract	Cancer is one of the major health concerns and leading causes of mortality worldwide. The major problem in the cancer chemotherapy is the drug-resistant of the established drugs. Therefore, the immediate search for anti-cancer agents from plant sources has been done intensively. The purpose of this study was to evaluate the anticancer effects of Alpinia galanga extracts against several breast cancer cell lines. The crude extracts were isolated via aqueous and different polarity of solvents such as hexane, acetone and ethanol using soxhlet extraction rotary evaporator. Cytotoxicity of crude extracts were screened by using MTT assay against normal human liver (WRL-68), and MCF-7, MDA-MB-231 and MDA-MB-468 breast cancer cell lines. Active crude extract with lowest IC50 value was selected for fractionated via column chromatography (CC) technique. Then, fractionates were re-evaluated for cytotoxicity profile and anti-migration activity. Further determination of active fraction induced cells death through cell cycle, apoptosis and pyroptosis was conducted flow cytometry and caspases bioluminescence studies. Their morphology structures were assessed under phase-contrast microscopy and inverted fluorescent-microscopy. Besides that, identification of bioactive molecules using gas chromatography-mass spectrophotometry (GC-MS) and prediction potential mechanism pathways was conducted through in silico molecular docking study. Active hexanic A. galanga extract with lowest IC50 value at 2.12 μg/mL and highest selectivity index (10.17) against MDA-MB-231 cells was fractionated. It was revealed that fraction F6-4 possessed potent anticancer and anti-migration activities. Interestingly, fraction F6-4 demonstrated both apoptosis and pyroptosis-induce cells death which involves ATP-dependent in MDA-MB-231 cells. The inhibition of MDA-MB-231 cells was characterized with apoptosis cells positive Annexin-V FITC due to exposure of phosphatidylserines (PS) on cell membrane after treatment and underwent cell cycle arrest at G0/G1 checkpoint. Further, the molecular mechanisms of inhibition of MDA-MB-231 cells by fraction F6-4 emphasizes on activation extrinsic and intrinsic caspases cascade, including inflammation caspase-1 (pyroptosis). Also, distinctly apoptosis and pyroptosis morphological changes were observed. Concomitantly, major bioactive compound was identified in both hexanic A. galanga and fraction F6-4 is 4-Chromanol. In silico molecular docking elucidated that 4-Chromanol induced apoptosis mechanisms through interaction between molecular extrinsic and intrinsic pathways, and also reveals as strong competitive inhibitor against Cdk2 and Cdk6. In conclusion, 4-Chromanol exhibited potent anticancer against triple negative breast cancer (TNBC) subtype and elucidate possible underlying mechanism(s) of apoptosis pathways.
dc.description.sponsorship	Faculty of Science
dc.identifier.uri	http://openscience.utm.my/handle/123456789/460
dc.language.iso	en
dc.publisher	Universiti Teknologi Malaysia
dc.subject	Phytochemicals
dc.subject	Antineoplastic agents
dc.subject	Plant biomass
dc.subject	Breast--Cancer
dc.title	Phytochemical, in vitro and in silico analyses of hexanic alpinia galanga extract in cancer chemo-prevention study on breast cancer cells
dc.type	Thesis
dc.type	Dataset

Phytochemical, in vitro and in silico analyses of hexanic alpinia galanga extract in cancer chemo-prevention study on breast cancer cells

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