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PENINGKATAN EFEK SITOTOKSIK DOXORUBICIN OLEH NARINGENIN MELALUI PEMACUAN APOPTOSIS SEL KANKER PAYUDARA MCF-7

Jurnal Bahan Alam Indonesia Vol 7, No 3 (2010)
Publisher : Indonesian Research Gateway

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Abstract

Chemoterapic agent doxorubicin has a lot of side effects and resistance problem. Therefore, it is important to develop combination treatment of doxorubicin with natural product (co-chemotheraphy) such as naringenin. Naringenin has been proven to have cytotoxic activity against several cancel cell lines. Naringen also increase the sensitivity of MCF-7 breast cancer cell towards doxorubicin. The aim of this research is to examine the synergistic effect of naringenin on the cytotoxic activity of doxorubicin through apoptosis induction of MCF-7 cancer cell lines.The cytotoxic assay of naringenin and doxorubicin were carried out by MTT method using naringenin concentrations of 100-1250 μM and doxorubicin concentrations of 50-800 nM to determine the IC50. Based on the IC50 values, the cytotoxic assay of their combination were carried out  by MTT method using concentration of ⅛, ¼, ⅜ and ½ IC50 values. Apoptosis assay of their best combination concentrations were done using double staining method.Naringenin and doxorubicin showed cytotoxic effect on MCF-7 breast cancer cell with IC50 of 520 μM and 467 nM, respectively. Based on CI values, almost all concentration combination of naringenin and doxorubicin showed synergistic effect (CI 0,1-0,9). This synergistic effect is due to the induction of apoptosis, showed by the increasing number of orange fluorescence cells in double staining method. Based on this results, naringenin was potential to be delevoped as co-chemotherapeutic agent. However, the molecular mechanism need to be explored further.

MCF-7 Resistant Doxorubicin are Characterized by Lamelapodia, Strong Adhesion on Substrate and P-gp Overexpression

Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Abstract

The  prognosis  of  breast  cancer  patients  is  closely  associated  with  the  response  of tumor  cells  to  chemotherapy  agent.  Doxorubicin  is  one  of  the  primary  chemotherapeutic agents  used  for  the  treatment  of  breast  cancer.  Resistance  to  chemotherapy  is  believed  to cause  treatment  failure  in  cancer  patients.  Furthermore,  long  time  exposure  to chemotherapeutic  agent  induces  cancer  cells  resistance.  MCF-7  sensitive  cells  used  as chemoresistance  model  have  overexpression  P-gp  (P-glycoprotein).  Chemoresistance  was established by treating MCF-7 cells with 0.5 µg/ml doxorubicin-contained medium for a week. 50% inhibiting concentration (IC50) doxorubicin on MCF-7 cells/DOX were determined using MTT assay. Western blot assay and immunocytochemistry assay was performed to determine the expression of P-gp. Morphological of MCF-7 cell/DOX was changing to become larger and have  lamellapodia.  IC50  value  of  doxorubicin  was  700  nM  on  MCF-7/DOX  and  400  nM  on sensitive MCF-7 cells. The MCF-7/DOX sensitivity to doxorubicin was decreased, shown by 1.5  fold  higher  IC50  of  doxorubicin  on  MCF-7/DOX  compared  to  MCF-7  sensitive  cells. Treatment doxorubicin to sensitive MCF-7 cells leads to the increasing P-gp expression. The P-gp  level  expression  has  strong  correlation  with  the  low  sensitivity  of  MCF-7/DOX  to doxorubicin.Key words: doxorubicin, resistance cells, sensitive MCF-7 cell

Hesperidin Increases Cytotoxic Effect of 5-Fluorouracil on WiDr Cells

Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Therapy  of  colon  cancer  by  using  5-FU  often  causes  problems  of  resistance.  This encourages the development of co-chemotherapy agent. One of the compounds that could potentially be used as a co-chemotherapy agent  is hesperidin. This study was conducted to determine the cytotoxic effects of hesperidin, 5-FU and the combination of them, as well as apoptosis induction in colon cancer cells WiDr. Cytotoxic effect of hesperidin, 5-FU, and its combination were observed using MTT assay. Observation of apoptosis was done by double staining method using ethidium bromide-acridin orange. Until 48 hours incubation, hesperidin showed no cytotoxic effects. Cytotoxic effects of 5-FU was observed after 48 hours with the IC50 value of 422 µM. However, hesperidin improved the cytotoxic effects of 5-FU at 48 hour incubation.  Either  single  treatment  of  hesperidin  200µM  or  5-FU  1500  µM  did  not  trigger apoptosis, but combination of them led to the emergence of signs of apoptosis. Based on this study,it can be concluded thathesperidin is potential to be developed as a co-chemotherapy agent of 5-FU on colon cancer but still need further study on its molecular mechanisms.Keywords : hesperidin, 5-fluorouracil, WiDr cells, cytotoxic, apoptosis

PENINGKATAN EFEK SITOTOKSIK DOXORUBICIN OLEH NARINGENIN MELALUI PEMACUAN APOPTOSIS SEL KANKER PAYUDARA MCF-7

Jurnal Bahan Alam Indonesia Vol 7, No 3 (2010)
Publisher : Indonesian Research Gateway

Show Abstract | Original Source | Check in Google Scholar

Abstract

Chemoterapic agent doxorubicin has a lot of side effects and resistance problem. Therefore, it is important to develop combination treatment of doxorubicin with natural product (co-chemotheraphy) such as naringenin. Naringenin has been proven to have cytotoxic activity against several cancel cell lines. Naringen also increase the sensitivity of MCF-7 breast cancer cell towards doxorubicin. The aim of this research is to examine the synergistic effect of naringenin on the cytotoxic activity of doxorubicin through apoptosis induction of MCF-7 cancer cell lines.The cytotoxic assay of naringenin and doxorubicin were carried out by MTT method using naringenin concentrations of 100-1250 μM and doxorubicin concentrations of 50-800 nM to determine the IC50. Based on the IC50 values, the cytotoxic assay of their combination were carried out  by MTT method using concentration of ⅛, ¼, ⅜ and ½ IC50 values. Apoptosis assay of their best combination concentrations were done using double staining method.Naringenin and doxorubicin showed cytotoxic effect on MCF-7 breast cancer cell with IC50 of 520 μM and 467 nM, respectively. Based on CI values, almost all concentration combination of naringenin and doxorubicin showed synergistic effect (CI 0,1-0,9). This synergistic effect is due to the induction of apoptosis, showed by the increasing number of orange fluorescence cells in double staining method. Based on this results, naringenin was potential to be delevoped as co-chemotherapeutic agent. However, the molecular mechanism need to be explored further.

EFEK SITOTOKSIK EKSTRAK ETANOLIK HERBA SELEDRI (Apium graveolens L.) PADA SEL KANKER T47D, WiDr, DAN HeLa

Farmasains Vol 1, No 2 (2011): Oktober 2010 - Maret 2011
Publisher : UMM Press

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Abstract

Celery (Apium graveolens L.) is commonly used to lower blood pressure, antirheumatic, relaxant, mild diuretic, antiseptic for the urinary tract, antioxidant, and anti-inflammation. According to previous studies, a number of the phytochemicals found in the plant show cytotoxicity toward some types of cancer cells. However, studies on the cytotoxic effects of celery herb ethanolic extract (CEE) on breast cancer cell (T47D), colon cancer cell (WiDr), and cervix cancer cell (HeLa), however, has not been done yet. Our research aims at doing so. Cytotoxicity test was conducted using MTT assay and its absorbance was read using ELISA reader at λ = 595 nm. Results of the assay show that CEE reduces cell viability at concentrations of 100-750 µg/ml on HeLa cells, while reduction of T47D and WiDr cell viability was not achieved until concentrations of 500-750 µg/ml. Based on these results, we conclude that CEE hold many potentials for further developments as preventive and therapeutive agent in cancer treatment.