Synergistic effects between 9-methoxycanthin-6-one when combined with selected chemo-drugs in inhibiting the proliferations of ovarian cancer cells
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1
Forest Research Institute Malaysia (FRIM), Malaysia
Background
The main modality of treatments for advanced ovarian cancer is still chemotherapy. However, significant numbers of patients still could not survive due to drug resistance and toxicity problems. The combination treatments are becoming one of the improved method to increase drug efficacy and reduce these problems clinically. However, more new drug candidates with different modes of action and positive druglikeness activities are still needed since different patients have different susceptibility on the drug uptake. An alkaloid compound had been isolated from the roots of Eurycoma longifolia and characterized as 9-methoxycanthin-6-one (EL50). EL50 was found to have anti-proliferative effects when tested in vitro and in vivo in our previous studies. The objective of this study was to evaluate if there is any synergism on the anti-proliferative activities when EL50 was combined with either cisplatin, paclitaxel, gemcitabine or doxorubicin.
Methods
The compound was used to treat ovarian cancer cell line (SKOV-3), either alone or in combination with chemotherapy drug (either cisplatin, paclitaxel, doxorubicin or gemcitabine). The combination treatments were performed either by simultaneous addition or sequential addition (either EL50 was added first, followed by the drug four hours later or vice versa). The results were evaluated after performing Sulforhodamine B assay using IC50 values for single treatment or combination index (CI) at different inhibition concentrations for binary treatments. CI values <1, =1 and >1 indicate synergism, additivity and antagonism in combined drug action, respectively.
Results and Conclusion
Initial studies had found that EL50 gave IC50 values were 1.70 ± 0.20, 1.65 ± 0.06 and 1.72 ± 0.18 µg/mL, respectively when treated in A2780, A2780cisR and SKOV-3 ovarian cancer cells. All the combination treatments were found to have synergistic effects (CI < 1) in inhibiting the proliferations of ovarian cancer cells when EL50 was added simultaneously with each of the mentioned drug, in which, highest synergism was found when EL50 was combined with paclitaxel. For sequential addition, it was found that highest synergism was shown when EL50 was added four hours before gemcitabine.
Keywords:
simultaneous addition,
Combination index (CI),
ovarian cancer,
9-methoxycanthin-6-one (EL50),
Eurycoma longifolia
Conference:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019.
Presentation Type:
Poster Presentation
Topic:
Cancer
Citation:
Yunos
NM,
Mat Amin
N,
Jauri
M,
Ling
KS,
Hassan
N,
Osman
A and
Abdullah
M
(2019). Synergistic effects between 9-methoxycanthin-6-one when combined with selected chemo-drugs in inhibiting the proliferations of ovarian cancer cells.
Front. Pharmacol.
Conference Abstract:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”.
doi: 10.3389/conf.fphar.2018.63.00009
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Received:
08 Nov 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Dr. Nurhanan M Yunos, Forest Research Institute Malaysia (FRIM), Kuala Lumpur, Malaysia, hanan@frim.gov.my