STUDY THE POTENTIAL KOKEMOTERAPI COMPOUNDS POTASSIUM PENTAGAMAVUNON-0 (K PGV-0) doxorubicin ON APOPTOSIS, CELL CYCLE, AND MODULATION METASTASIS IN BREAST CANCER
ABSTRACT: A salt compound of curcumin analogue, potassium pentagamavunon-0 (KPGV-0) has been synthesized to improve solubility of pentagamavunon-0 which has been proven to have anti-proliferative effect on several cancer cells. The purpose of this study is to investigate cytotoxic activity and metastasis inhibition of K PGV-0 alone and its combination with chemotherapeutic agent, doxorubicin (dox) on breast cancer cells. In this study, cytotoxic activity of K PGV-0 and its combination with doxorubicin (K PGV-0+dox) on T47D and 4T1 breast cancer cells were analyzed by using MTT assay. Cell cycle modulation and apoptosis induction were examined by flowcytometer. To investigate metastasis inhibiton of K PGV-0 and K PGV-0+dox, scratch wound healing assay and gelatin zymography were conducted. The result showed that K PGV-0 has cytotoxic activity on T47D and 4T1 with IC50 value 94,94 µM dan 48,97±0,2 µM, respectively. In general, K PGV-0+dox revealed synergistic effect and decreased cell viability up to 84,69 % on T47D cells and 62,6 % on 4T1 cells. K PGV-0 and K PGV-0+dox caused cell accumulation in G2/M phase and apoptosis induction. In the process of cancer metastasis, K PGV-0 alone did not show inhibition of 4T1 cell migration, whereas K PGV-0+dox inhibited cell migration. The compoud, K PGV-0 and its combination with dox inhibited the activity of MMP-9 which has pivotal role in extracellular matrix degradation. These result show that combination of K PGV-0 and doxorubicin inhibit cancer cell growth through cell cycle inhibition, apoptosis induction, and inhibition of cell migration and MMP-9 activity. Therefore, K PGV-0 performs potency to be developed as co-chemotherapeutic agent.
