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All Journal Indonesian Journal of Cancer Chemoprevention
. Anindyajati
Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta
Articles
6
Documents
Combination of Solanum nigrum L. Herb Ethanolic Extract and Doxorubicin Performs Synergism on T47D Breast Cancer Cells

Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Research Gateway

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Abstract

Leunca (Solanum nigrum L.) has been proven to possess  anticancer activity on some type of cancer cells. In vitro study of solamargine found in the herb showed cytotoxic effect against several breast cancer cell lines, such as T47D and MDA-MB-31. Hence, further study on its potential as a co-chemotherapeutic agent needs to be conducted, in order to overcome resistance problem commonly found in cancer  chemotherapy. This study aimed to examine the cytotoxic activity of leunca herb ethanolic extract (LEE) alone and its combination with doxorubicin. Single and combinational treatment of LEE and doxorubicin on T47D breast cancer cells were done, and their viability representing cytotoxicity were analyzed by using MTT assay to determine the IC50 value and combination index (CI) to evaluate the combinational effect.  Twenty four hours-treatment of LEE  alone gave cytotoxicity activity showing a dose-dependent manner with the IC50 of 47 µg/ml, while combinational treatment showed that 4 µg/ml LEE was found to be synergist with 4 nM doxorubicin on T47D cells, with the optimum CI value of 0.59. This result shows that Solanum nigrum L. is potential to be proposed as doxorubicin co-chemotherapeutic agent against breast cancer. Further study on its molecular mechanism needs to be conducted.

Ficus septica burm. F. Leaves Ethanolic Extract Induces Apoptosis in 7,12-dimethylbenz[a]nthracene-induced Rat Liver Cancer Quatitavely

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

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Abstract

The chemopreventive effect of  Ficus septica Burm. f. leaves ethanolic extract (FLEE) was studied in 7,12-dimethylbenz[a]nthracene (DMBA)-induced rat liver cancer. Rats were divided into 5 group, 5 rats (5 wk of age Sprague Dawley rat) in each group. Group 1 was control diet group, administered with 0,5% CMC-Na as vehicle. FLEE was administered 750 mg/kgBW and 1500 mg/kgBW starting 4 wk until 5 wk after DMBA administration at the first until fifth wk to group 2 and group 3. Group 4 was control extract group, administered  with 750 mg/kgBW and  group  5  was  DMBA  group.  DMBA  is  a  carcinogen  to  induce  liver  cancer  was  also administered in DMBA control group and all animals were necropsied at 6 wk after DMBA administration. Activity of inducing apoptosis was detected using Double Staining method in 750 mg/kgBW FLEE group compared to control group but no in 1500 mg/kgBW FLEE group resulted in 100% dead. Apoptotic cells would have orange flourescence but normal cells would have green flourescence detected by flourescence microscope. To investigate the protein that involved in apoptotic mechanism, we studied p53 expression using Imunohistochemistry (IHC). There was no difference expression of p53 in both tested and control groups. Based on the results, FLEE has a potency as chemoprentive agent because its activity on inducing apoptosis in liver  cancer  with  p53-independent  pathway.  The  mechanism  of  apoptosis  induction  of  this extract needs to be explored by observing the expression of related proteins. Key words: apoptosis, Ficus septica, liver cancer, p53 independent pathway

Combination of Leunca Herb Ethanolic Extract and Doxorubicin Suppresses HeLa Cells’ Growth

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

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Abstract

Leunca (Solanum nigrum L.)ethanolic extractshowedcytotoxic activity on several cancer cell lines (HepG2, HT-29) and showed anti-proliferative activityon MCF-7 cells. Its application as a combinationagent in chemotherapy will increase  the effectivity and reduce  the toxicity of chemotherapy. We predict that application of combinatorial chemotherapy in cancer treatment will  be  more  effective  and  less  toxic  compared  to  single  treatment.  Our  research  aims  to investigate  the  cytotoxic  activitiy  of  leunca  herbs  ethanolic  extract  alone  and  in  combination with  doxorubicin  on  HeLa  cell  line.  MTT  assay  was  conducted  to  measure  the  growth inhibitory  effect  of  leunca  herbs  ethanolic  extract  and  combinatorial  treatments.  Leunca  herb ethanolic extract (5, 50, 250 μg/ml) increased the cytotoxic effect of  doxorubicin compared to doxorubicin alone. The strongest cytotoxic activity resulted from the combination of 250 μg/ml leunca  herbs  ethanolic  extract  and  250  nM  doxorubicin.  Based  on  our  results,  leunca  herbs ethanolic extract is a potential chemopreventive agent, while its molecular mechanism needs to be explored.Keyword : Leunca herbs ethanolic extract, doxorubicin, HeLa, MTT assay

Ficus septica Burm.f. Leaves Ethanolic Extract Triggered Apoptosis on 7,12-Dimethylbenz[a]anthracene-Induced Rat Mammary Carcinogenesis Qualitatively

Indonesian Journal of Cancer Chemoprevention Vol 3, No 1 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Ficus septica Burm.f.ethanolic extract (FEE) shows cytotoxic effects on several cancer cell lines. Our research aimed to investigate the effect of FEE on apoptosis induction and p53 expression against carcinogenesis of 7,12-Dimenthylbenz[a]anthracene (DMBA)-induced rat mammary. The research was conducted by comparing both apoptosis induction and p53 expression in DMBA-induced rats that were treated with FEE against control groups. Cells that undergo apoptosis were visualized by Double Staining method with acridine orange and ethidium bromide, while p53 expression was detected by IHC staining. Double staining result showed increased occurrence of apoptotic cells compared to the control groups. IHC staining pf P53 did not show significant difference between treatment and control groups. However, FEE was able to repair morphology of cells undergoing carciogenesis. Thus, we conclude that FEE has an anti carciogenic activity on DMBA-induced rat mammary through apoptosis induction without affecting p53 expression. Therefore, the ethanolic extract of Ficus septica leaves is a potential chemo-preventive agent on breast cancer. Further study on its molecular mechanism needs to be exploredKeywords: Ficus septica, breast cancer, 7,12-Dimethylbenz[a]anthracene, carciogenesis, apoptosis, p53

Ursolic Acid Enhances Doxorubicin Cytotoxicity on MCF-7 Cells Mediated by G2/M Arrest

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

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Abstract

Ursolic acid has been widely known to possess biological activity against numerous tumor cell lines. Previous studies revealed its cytotoxicity on several cancer cells  in vitro by either inducing apoptosis or cell cycle modulation. This  study was conducted to investigate ursolic  acid’s  cytotoxicity  solely  and  in  combination  with  a  chemotherapeutic  agent, doxorubicin,  on  MCF-7  breast  cancer  cells,  followed  by  observation  on  its  mechanism. Cytotoxicity of single and combinational treatment of ursolic acid and doxorubicin on MCF-7 breast cancer cells were conducted by using MTT assay. Single treatment was then evaluated by  determining  IC50  value,  while  combinational  treatment  was  evaluated  by  analyzing  cell viability  and  evaluating  combination  index  (CI).  To  explore  the  mechanism  underlying cytotoxic  effect  on  respected  cells,  further  analysis  on  cell  cycle  profile  of  single  and combinational treatment was conducted by flow cytometry. Twenty four hours treatment of ursolic  acid  inhibited  MCF-7 cells’ growth with  IC50  value  of  37  µM,  while  combinational treatment  showed  that  several  concentration  combinations  of  ursolic  acid  and  doxorubicin exhibited  synergism  of  cytotoxic  activity  on  MCF-7  cells,  giving  optimum  CI  value  of  0.54. Flow cytometric analysis showed that combinational treatment induced G2/M arrest in MCF-7  cells.  These  results  show  that  ursolic  acid  is  promising  to  be  developed  as  either  single chemopreventive  agent,  or  as doxorubicin’s co-chemotherapeutic  agent  in  breast  cancer treatment.  Observation  on  the  selectivity  as  part  of  safety  aspect  together  with  in silico,  in vitro, and in vivo study on its molecular mechanism should be conducted.Keywords: ursolic acid, doxorubicin,co-chemotherapeutic agent, breast cancer, cell cycle

Translational Research in Cancer Drug Development

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

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Abstract

The development of cancer treatment were initiated by the existence of human’s effort to treat by applying certain materials which is mostly part(s) or extracts of plants, which are now adapted as traditional herbal medicine. The discovery of new drugs was based on intuition and empirical evidence. Thus, high luck factor was involved in a successful treatment with unguaranteed reproducibility. One example of drug being developed through conventional drug development is Taxol. Taxol is an extremely complex natural product and requires a bunch of hard work with high level of serendipity to be discovered as antitumor agent. Recently, rapid development in human biology and technology allow a change in drug discovery strategy by minimizing the luck factor. Targeted therapy has been a very promising strategy of drug development research, especially in cancer treatment. Although cancer has been known as a disease with very complex cellular and histo-pathophysiology, the abundance of studies on proteins, such as receptors and hormones, as the hallmarks of cancer allows us to explore carcinogenesis suppression further based on molecular targeted therapy. Kinases, one type of protein involved in signal transduction regulating cell growth and differentiation, could be the proteins that  are proposed to be inhibited in suppressing tumor growth. An interesting example of the drug being discovered based on molecular modeling is the discovery of lapatinib as anti-cancer with specific target on HER-2 and EGFR to overcome the resistance of cancer  to Herceptin caused by elevated level of EGFR expression.