PGV-0 AND PGV-1 INCREASED APOPTOSIS INDUCTION OF DOXORUBICIN ON MCF-7 BREAST CANCER CELLS
ABSTRACT: As chemotherapeutic
backbone for breast cancer therapy, doxorubicin showed various side effects and
induced resistancy of breast cancer cells. Development of targeted therapy on
breastcancer focused on combinatorial therapy of doxorubicin and molecular
targeted agents. PGV-0 andPGV-1, a curcumin analogue showed potency as
co-chemotherapeutic agent with doxorubicin. Ourprevious study of PGV-0 and
PGV-1 showed cytotoxic activity in T47D cells. Therefore, the aim ofthis
research is to examine the synergistic effect of PGV-0, PGV-1 on the cytotoxic
activity ofdoxorubicin through cell cycle modulation and apoptotic induction on
MCF-7 breast cancer celllines. The cytotoxic assay of PGV-0, PGV-1,
doxorubicin, and their combination were carried out by using MTT assay. Cell
cycle distribution and apoptosis were determined by flowcytometer FACSCalibur
and the flowcytometry data was analyzed using Cell Quest program. Single
treatment of PGV-0, PGV-1 and doxorubicin showed cytotoxic effect on MCF-7 with
cell viability IC50 value 50µM, 6 µM and 350 nM respectively. Single treatment
of Doxorubicin 175 nM induced G2/M arrest.Single treatment of PGV-0 5 µM
induced G2/M arrest while in higher dose 12.5 µM, PGV-0 induced apoptosis.
Combination of doxorubicin 175 nM and PGV-0 5 µM induced apoptosis. Combination
of doxorubicin 175 nM and PGV-0 12.5 µM also increased apoptosis induction.
Single treatment of PGV-1 0.6 µM induced G1 arrest while in higher dose 1.5 µM,
PGV-1 induced apoptosis. Combination of doxorubicin 175 nM and PGV-1 0.6 µM
induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 1.5 µM also
increased apoptosis induction. PGV-0 and PGV-1 are potential to be delevoped as
co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell
cycle modulation, but the molecular mechanism need to be explored detail.
Key words: PGV-0, PGV-1,
doxorubicin, co-chemotherapy, breast cancer, cell cycle arrest, apoptosis
Penulis: Adam Hermawan
Kode Jurnal: jpfarmasidd110169
