POTENSI KO-KEMOTERAPI Gynura procumbens (Lour.) Merr. PADA KANKER KOLON DAN KANKER PAYUDARA: PENENTUAN TARGET SERTA MEKANISME MOLEKULERNYA
Colon and breast cancers are the common malignant neoplasma with high incidence and cause more than 30 % of patient death. Although there has been improvement in survival with chemotherapy, non specific drug targeting cause serious side effects and the acquisition of multidrug resistance (MDR. There...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Theses and Dissertations NonPeerReviewed |
| Published: |
[Yogyakarta] : Universitas Gadjah Mada
2012
|
| Subjects: | |
| Online Access: | https://repository.ugm.ac.id/99020/ http://etd.ugm.ac.id/index.php?mod=penelitian_detail&sub=PenelitianDetail&act=view&typ=html&buku_id=55342 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Institution: | Universitas Gadjah Mada |
| Summary: | Colon and breast cancers are the common malignant neoplasma with high
incidence and cause more than 30 % of patient death. Although there has been
improvement in survival with chemotherapy, non specific drug targeting cause
serious side effects and the acquisition of multidrug resistance (MDR. There are
major obstacles in anticancer treatment. Several studies showed the emergence of
MDR has associated with the increasing level of the membrane glycoprotein, Pglycoprotein
(P-gp). Treatment of cancer cells with chemotherapeutic agent such
as anthracycline results in induction of P-gp expression. New efforts are using
natural substance with low or moderate toxicity, as co-chemotherapeutic agent
for boosting the efficacy of the main chemotherapeutic agent. This study was
designed to investigate whether the ethyl acetate fraction of Gynura procumbens
(FEG) could improve cisplatin (CISP)and 5-fluorouracil (5-FU) potency on colon
cancer and doxorubicin (DOX) and 5-fluorouracil (5-FU) on breast cancers. We
also want to examine whether FEG could suppress and overcome the cell
resistance development through its modulation to P-gp expression.
FEG in combination with 5-FU shows additive effect on WiDr but exhibits
antagonism when combined with Cisplatin (CISP). Both of DOX+FEG and 5-
FU+FEG produce strong synergistic effect on MCF-7 and T47D. The
combination treatment of DOX+FEG and 5-FU+FEG enhanced the G1 arrest of
WiDr, MCF-7 and T47D with the appearance of a sub G1 peak indicating
apoptosis/necrosis. The apoptosis induction phenomenon was supported by DNA
fragmentation and the increasing of cPARP expression after combination
treatment of DOX+FEG and 5-FU+FEG on MCF-7. No significance DNA
fragmentation and nucleus condensation at T47D after DOX, 5-FU, and FEG as
single and combination treatment. Only combination of 5-FU+FEG shows cPARP
expression in this cell. We propossed other type of FEG-mediated cell death on
T47D cells beside apoptosis. FEG treatment also caused the decreasing of
microtubule expression as shown by Western blotting assay. The decreasing level
of this protein may cause by protein aggregation, as shown by immunostaning
using α-tubulin antibody. FEG treatment in subtoxic concentration could decrease
P-gp expression at breast cancer cell resistance model. MCF-7/DOX were
developed by inducing MCF-7 with subtoxic concentration of DOX (100 nM) for 5
(five) months. The usage of FEG as co-chemotherapeutic agent with DOX
exhibited the enhancement of DOX effect on MCF-7/DOX cell growth. This
inhibition effect higher compared with DOX+FEG effect on MCF-7 wild type.
All these results support the suggestion that FEG potentiates the DOX and
5-FU efficacy on breast cancer. The FEG may have specific targeted on
microtubule integrity modulation. FEG could reverse MDR by inhibition the P-gp
expression. FEG could be developed potentially as co-chemotherapeutic agent for
reducing side effect and reverse MDR at breast cancer treatment. |
|---|