Antitumour activity of SRJ13, a new derivative of andrographolide, against breast cancer cell lines / Nor Hafizah Hassan

Breast cancer is the most common cancer among women. Chemotherapy is not selective in its therapeutic effects. Hence, the occurrence of many side effects. The tendency of breast cancer developing resistance towards standard anticancer agent is also a great hurdle yet to be overcome. Thus, the discovery of a novel anticancer agent is vital. SRJ13 is a semisynthetic compound, derived from andrographolide. Previous studies revealed that andrographolide possess antitumor activity against various types of human cancers including breast cancers. Therefore, SRJ13 might exhibit better antitumour effect. This study aimed to investigate the antitumor activity of SRJ13 against different breast cancer cell lines. MCF7 and T47D are both hormone-dependent cell lines whereas MDA-MB-231 and MDA-MB-468 are both hormone-independent. Another objective of this study is to compare the anticancer activity of SRJ13 against these breast cancer cell lines to that of the andrographolide and tamoxifen. The potential synergistic interaction between SRJ13 and tamoxifen against MCF7 and MDA-MB-468 would also be investigated. The cell cultures were sustained by RPMI 1640, supplemented with 10% FBS and 1% penicillin-streptomycin. The breast cancer cells were then treated singly with the respective agents at different concentrations, ranging from 0.1 pM to lOOpM. The cells were incubated for 96 hours after which viability of the cells was determined using the MTT assay. Data generated from the microplate reader was used to plot the dose response curve. As for the concomitant treatment of SRJ13 and tamoxifen, the procedures stated above apply. The concentration range of both agents was between 2 times to 0.2 times of their respective GI50. Data obtained were then analysed using the median effect analysis. Findings of this study showed that SRJ13 had reduced the growth of all the breast cancer cell lines. SRJ13 is most effective against MDA-MB-468. When compared the anticancer activity of SRJ13 to that of the andrographolide, results showed that andrographolide is more potent against all the breast cancer cell lines except for MCF7. However, further statistical analysis revealed that the differences observed between SRJ13 and tamoxifen are insignificant. Interestingly, SRJ13 had been found to be a better choice of anticancer agent compare to tamoxifen when treated against MDA-MB-231 and MDA-MB-468 (p<0.05). As for combination treatment of SRJ13 and tamoxifen against MDA-MB-468, the overall inhibiting effects were found statistically insignificant. However, synergistic effect of the combination treatment was observed at two times GI50 of the respective drugs which treated against MDA-MB-468. The potential of SRJ13 being used in combination with other standard agents should be investigated more extensively. Further studies should also be conducted to uncover its mechanism of action and pharmacokinetic profile.