NCI in vitro and in silico anticancer screen, cell cycle pertubation and apoptosis-inducing potential of new acylated, benzylidene and isopropylidene derivatives of andrographolide

Charng Choon Wong, Sreenivasa Rao Sagineedu, Shariful Hasan Sumon, Shiran Mohamad Sidik, Roger Phillips, Nordin H. Lajis, Johnson Stanslas

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Andrographolide (AGP) is the main bioactive constituent isolated from the traditional medicinal, Andrographis paniculata which contributes towards its various biological activities, including anticancer property. In this study, a series of new AGP derivatives were semi-synthesised and screened against the NCI in vitro 60 cell lines. From the screening results, we had identified SRS07 as the most potent AGP derivative, against breast and colon cancer cell lines. Subsequently, SRS07 was tested for its capability to induce cell cycle arrest and apoptosis in MCF-7 and HCT116 cancer cells. SRS07 effectively induced G1 cell cycle arrest in both cell lines and ultimately apoptosis by inducing DNA fragmentation in HCT116 cells. The apoptotic cell death induced by SRS07 was confirmed via FITC Annexin-V double staining. Western blot analysis of SRS07-treated HCT116 cells revealed that the compound induced apoptosis be activating caspase 8 which in turn cleaved Bid to t-Bid to initiate cell death cascade. Prediction of the possible mode of action of SRS07 by utilising NCI COMPARE analysis failed to reveal a distinct mechanism category. Hence, it is speculated that SRS07 possesses novel mechanism of action. In conclusion, SRS07 demonstrated superior in vitro anticancer profiles and emerged as a potential lead anticancer candidate.

Original languageEnglish
Pages (from-to)489-501
Number of pages13
JournalEnvironmental Toxicology and Pharmacology
Volume38
Issue number2
Early online date7 Aug 2014
DOIs
Publication statusPublished - Sep 2014
Externally publishedYes

Fingerprint

HCT116 Cells
Computer Simulation
Cell Cycle
Cells
Apoptosis
Derivatives
Cell Line
Cell Death
Andrographis
G1 Phase Cell Cycle Checkpoints
Caspase 8
Fluorescein-5-isothiocyanate
Annexin A5
DNA Fragmentation
Cell death
Cell Cycle Checkpoints
Colonic Neoplasms
Western Blotting
Staining and Labeling
Breast Neoplasms

Cite this

Wong, Charng Choon ; Sagineedu, Sreenivasa Rao ; Sumon, Shariful Hasan ; Sidik, Shiran Mohamad ; Phillips, Roger ; Lajis, Nordin H. ; Stanslas, Johnson. / NCI in vitro and in silico anticancer screen, cell cycle pertubation and apoptosis-inducing potential of new acylated, benzylidene and isopropylidene derivatives of andrographolide. In: Environmental Toxicology and Pharmacology. 2014 ; Vol. 38, No. 2. pp. 489-501.
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NCI in vitro and in silico anticancer screen, cell cycle pertubation and apoptosis-inducing potential of new acylated, benzylidene and isopropylidene derivatives of andrographolide. / Wong, Charng Choon; Sagineedu, Sreenivasa Rao; Sumon, Shariful Hasan; Sidik, Shiran Mohamad; Phillips, Roger; Lajis, Nordin H.; Stanslas, Johnson.

In: Environmental Toxicology and Pharmacology, Vol. 38, No. 2, 09.2014, p. 489-501.

Research output: Contribution to journalArticle

TY - JOUR

T1 - NCI in vitro and in silico anticancer screen, cell cycle pertubation and apoptosis-inducing potential of new acylated, benzylidene and isopropylidene derivatives of andrographolide

AU - Wong, Charng Choon

AU - Sagineedu, Sreenivasa Rao

AU - Sumon, Shariful Hasan

AU - Sidik, Shiran Mohamad

AU - Phillips, Roger

AU - Lajis, Nordin H.

AU - Stanslas, Johnson

N1 - No full text in Eprints. HN 29/11/2017

PY - 2014/9

Y1 - 2014/9

N2 - Andrographolide (AGP) is the main bioactive constituent isolated from the traditional medicinal, Andrographis paniculata which contributes towards its various biological activities, including anticancer property. In this study, a series of new AGP derivatives were semi-synthesised and screened against the NCI in vitro 60 cell lines. From the screening results, we had identified SRS07 as the most potent AGP derivative, against breast and colon cancer cell lines. Subsequently, SRS07 was tested for its capability to induce cell cycle arrest and apoptosis in MCF-7 and HCT116 cancer cells. SRS07 effectively induced G1 cell cycle arrest in both cell lines and ultimately apoptosis by inducing DNA fragmentation in HCT116 cells. The apoptotic cell death induced by SRS07 was confirmed via FITC Annexin-V double staining. Western blot analysis of SRS07-treated HCT116 cells revealed that the compound induced apoptosis be activating caspase 8 which in turn cleaved Bid to t-Bid to initiate cell death cascade. Prediction of the possible mode of action of SRS07 by utilising NCI COMPARE analysis failed to reveal a distinct mechanism category. Hence, it is speculated that SRS07 possesses novel mechanism of action. In conclusion, SRS07 demonstrated superior in vitro anticancer profiles and emerged as a potential lead anticancer candidate.

AB - Andrographolide (AGP) is the main bioactive constituent isolated from the traditional medicinal, Andrographis paniculata which contributes towards its various biological activities, including anticancer property. In this study, a series of new AGP derivatives were semi-synthesised and screened against the NCI in vitro 60 cell lines. From the screening results, we had identified SRS07 as the most potent AGP derivative, against breast and colon cancer cell lines. Subsequently, SRS07 was tested for its capability to induce cell cycle arrest and apoptosis in MCF-7 and HCT116 cancer cells. SRS07 effectively induced G1 cell cycle arrest in both cell lines and ultimately apoptosis by inducing DNA fragmentation in HCT116 cells. The apoptotic cell death induced by SRS07 was confirmed via FITC Annexin-V double staining. Western blot analysis of SRS07-treated HCT116 cells revealed that the compound induced apoptosis be activating caspase 8 which in turn cleaved Bid to t-Bid to initiate cell death cascade. Prediction of the possible mode of action of SRS07 by utilising NCI COMPARE analysis failed to reveal a distinct mechanism category. Hence, it is speculated that SRS07 possesses novel mechanism of action. In conclusion, SRS07 demonstrated superior in vitro anticancer profiles and emerged as a potential lead anticancer candidate.

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KW - Apoptosis

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KW - In silico

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