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All Journal Indonesian Journal of Cancer Chemoprevention
. Larasati
Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada Jalan Sekip Utara Sleman Yogyakarta 555281
Articles
3
Documents
Leunca (Solanum nigrum L.) Herbs Ethanolic Extract Increase Cytotoxic Activity of Cisplatin on Hela Cervical Cancer Cells

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

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Abstract

Cervical cancer is one of leading causes of cancer death in women in the developing countries. The use of cisplatin as chemotherapy agent in cervical cancer is known to cause side effects and also resistance for long-term uses. One of the strategies to prevent cervical cancer based on combination agents is being developed. Leunca (Solanum nigrum L.) has been revealed to inhibit growth of human cancer cells. Therefore, it can be used in combination with cisplatin to reduce those side effects and prevent the occurrence of cell resistance. Ethanolic extract of Leunca Herb (ELH) and cisplatin were tested their cytotoxic effect on HeLa cervical cancer cell by using MTT assay to determine IC50 value. The combinationss of cisplatin-ELH were tested to determine the combination index (CI value).  The IC50 of ELH and cisplatin on HeLa cells were 227 µg/mL and 17 µM. rRespectively. Tthe study of combination resulted that almost all the index combinations were <0,9 showed  the effect of synergism combination. The Ooptimum concentration of combination was  1/8 IC50 cisplatin–1/8 IC50 ELH. The results indicated that ELH had a potency to be combination agent to enhance the activity of cisplatin on HeLa cervical cancer cells. Therefore, further study on its molecular mechanism needs to be explored.

Hesperidin Increases Cytotoxic Activity of Doxorubicin on Hela Cell Line Through Cell Cycle Modulation and Apoptotis Induction

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

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Abstract

Combination of chemotherapeutic agent and chemo preventiveagent is being a new approach in cancer treatment.This is aimed at enhancing the effectivity and also reducing drugresistance and adverse side effect of the chemo therapeuticagent.Hesperidin,acitrus flavonoid has reported to reduce theproliferation of many cancer cells.The objectives of this study were to investigate cytotoxic activities, cell cycle modulation and apoptosis induction of he speridinand its combination withdoxorubicinon Helacelllines.MTT [3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazoliumbromide] assay was used tomeasure the growth inhibitory effect of he speridinanditscombination with doxorubicinon Helacells.Cellcycle profile was determined by flowcytometry and the dataobtained was analyzed by using Mod Fit LT3.0program.Apoptos is assay was done using double staining method usingethidium$bromideandacridine$orange.Hesperidin inhibited cellgrowth with IC5048M, while the IC50 of doxorubicin was 1000nM.Combination of 500n Mdoxorubicin and 6M hesperidin showed strongest inhibitory effect toward Hela cells. Hesperidin of 24 2M accumulated HeLacells at G1phase,butit scombinationwith 500nM Doxorubicin gave G1 and Sphase accumulation at 24h incubation.Both of Hesperidin and Doxorubicin were capable of inducing apoptosis.Inaccordance of the apoptoticeffect,hesperidin,doxorubicin and their combination decreasedthe expression Bcl$2 and increased the expression of Bax. Accordingtothisresult,hesperidinhasapotencytobedevelopedasco$chemotherapeutic agent forcervical cancer. Key    words:Cochemotherapy,Hesperidin,Doxorubicin,Hela,MTTassay

Naringenin Enhances the Anti-Tumor Effect of Doxorubicin on HeLa Cervical Cancer Cells Through Cytotoxic Activity and Apoptosis Induction

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

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Abstract

Naringenin, an abundant flavanon in the peel of citrus fruits is reported to possess anti-proliferative  effect  in  many  cancer  cells.  Herein,  we  investigated  the  cytotoxic  effect  and apoptosis  induction  of  naringenin  in  combination  with  doxorubicin  on  HeLa  cells.  The cytotoxicity assay of naringenin, doxorubicin, and their combination were carried out by using MTT  assay.  Cell  viability  was  used  as  the  parameters  to  evaluate  combination  effectiveness. Cell  cycle  distribution  was  determined  by  flow  cytometry  and  analyzed  using  ModFit  LT  3.0 program.  Apoptosic  assay  was  done  by  double  staining  method  using  Ethidium  Bromide-Acridine  Orange.  Investigation  on  the  expression  of  Bax  and  Bcl-2  were  determined  by immunocytochemistry method. Naringenin and doxorubicin showed cytotoxic effect  on HeLa cells  with  their  IC50  values  of  195  µM  and  1  µM,  respectively.  Whereas  combination  of naringenin  -  doxorubicin  showed  greater  cytotoxicity  compared  the  single  treatment  of doxorubicin.  The  strongest  cytotoxic  activity  was  observed  at  a  combination  of  100  µM naringenin  and  0,5  µM  doxorubicin.  Single  treatment  of  0,5  µM  doxorubicin  for  24  hours  on HeLa cells induced  S-phase arrest while 100 µM naringenin did not affect on HeLa cell cycle. The  combination  induced  S-phase  arrest  with  the  increased  of  sub-G1  phase  percentage.  In accordance with the flow cytometry results, the double staining apoptosis assay results showed the increase of apoptotic cells. Naringenin, doxorubicin, and their combination also increased the  expression  of  Bax  and  decreased  the  expression  of  Bcl-2.  These  results  concluded  that naringenin was a potential co-chemotherapy agent for cervical cancer due to its synergism with doxorubicin.Keywords:  co-chemotherapy,  naringenin,  doxorubicin,  HeLa  cells,  cytotoxicity,  cell  cycle, apoptosis