POTENSI KO-KEMOTERAPI Gynura procumbens (Lour.) Merr. PADA KANKER KOLON DAN KANKER PAYUDARA: PENENTUAN TARGET SERTA MEKANISME MOLEKULERNYA

• Main Authors: , Nunuk Aries Nurulita, , Prof. Dr. Sugiyanto, SU.,Apt.
• Format: Theses and Dissertations NonPeerReviewed
• Published: [Yogyakarta] : Universitas Gadjah Mada 2012
• Subjects: ETD
• 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
• Institution: Universitas Gadjah Mada

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.