Muthi Ikawati
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada
Articles
4
Documents
Aktivitas Antiproliferasi Ekstrak Etanolik Herba Ciplukan (Physalis angulata L.) Terhadap Sel Hepar Tikus Betina Galur Sprague Dawley Terinduksi 7,12-Dimetilbenz[a]antrasena

Majalah Kesehatan Pharmamedika Vol 3 N0 1 2011
Publisher : Majalah Kesehatan Pharmamedika

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Abstract

One of the natural materials as potentially efficacious chemopreventive agents are Ciplukan (Physalis angulata L.). Several previous studies reported that Physalis angulata L. herbs ethanolic extract (PEE) has cytotoxic activity and induction of apoptosis in breast cancer cells MCF-7 and HeLa cervical cancer cells. This study aims to determine the effects of  PEE as an chemopreventive agent on rat liver cells induced 7,12-dimetilbenz[a]anthracene (DMBA). This study used Sprague Dawley strain female rats aged 40-50 days were divided into 5 groups : (1) DMBA control group, mice were induced with DMBA in per oral dose of 20 mg/kg; (2) DMBA + PEE dose 750 mg/kgBW group ; (3) DMBA + PEE dose 1500 mg/kgBW group ; (4) solvent control group of CMC-Na 0,5%; (5) PEE dose 1500 mg/kgBW control group. PEE was dissolved in CMC-Na 0,5% and administered daily, starting the seventh week after administration of DMBA. At the beginning of  the tenth week of the study, rats were necropted and liver organs were isolated and stored in buffered formalin 4%. Qualitative analysis to determine the histopathology of liver cells through staining method of Hematoxyllin & Eosin (HE), while quantitative analysis to determine the level of liver cell proliferation by AgNOR staining method. The results showed in the DMBA control group that liver cell morphology changes that hiperproliferation leading to carcinogenesis. In DMBA + PEE dose of  1500 mg/kgBW group improved the situation of DMBA-induced liver cells histopathology and antiproliferation activity better than DMBA + PEE dose of 750 mg/kgBW on DMBA-induced rat liver cells. The results showed that Physalis angulata L. herbs ethanolic extract can inhibit cell proliferation in rat liver caused by DMBA administration through antiproliferation mechanism and have potential for the development as chemoprevention material on liver cancer

Taraxacum officinale Leaves Ethanolic Extract as Immunostimulatory Agent For Reducing Side Effect of Doxorubicin in Sprague Dawley Rats

Indonesian Journal of Cancer Chemoprevention Vol 2, No 1 (2011)
Publisher : Indonesian Research Gateway

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Abstract

Doxorubicin as chemotherapeutic agent causes immunosuppresive. The aim  for this study to determine the effect of ethanolic extract of Taraxacum oficinale (ETO) in immunity system of Sprague Dawley  rat that induced  by doxorubicin to observe the profile of immunity cells. Sprague Dawley rats were divided into five groups each groups contain five rats : control doxorubicin group, doxorubicin dose 4,67 mg/kgBW+ ETO dose 1000 mg/kgBW, doxorubicin dose 4,67 mg/kgBW+ ETO dose 500 mg/kgBW, control extract group, and without treatment. Then the number of leukocytes, lymphocytes and neutrophils were analyzed  by hematology analyzer, whereas CD8+ T lymphocytes by flowcytometry. Results showed groups of  doxorubicin combined with ETO dose 1000 mg/kgBW and 500 mg/kgBW increased the number of leukocytes, lymphocytes, neutrophils,  cytotoxic CD8 + T cells  T cells compared  to control doxorubicin group. These data presents that etanolic extract of Jombang leaves has  immunostimulatory activity and potential as co-chemotherapy agents. Molecullar mechanism underlaying it’s immune activity need to be explored in detail.

Banana Peels (Musa paradisiaca L.) Extract as Phytoestrogen on Ovariectomized Mice Mammary Gland Development by Inducing c-Myc Expression

Indonesian Journal of Cancer Chemoprevention Vol 2, No 1 (2011)
Publisher : Indonesian Research Gateway

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Abstract

Hormone Replacement Therapy (HRT) is therapy for estrogen deficiency and post menopausal  syndromes,  but  high  cost  and  unwell-secured  therapy.  One  of  alternative therapy  is  the  usage  of  phytoestrogens.  The  banana  peel  contains  flavones,  flavonol, flavanone and polimethoxyflavone which are potential as phytoestrogen. The purpose of this study was to examine the estrogenic effect of banana peel extract (BPE) development of mammary gland of ovariectomized rats. Estrogenic effects was examined based on in vivo and in silico experiment. For in vivo experiment, female Sprague-dawley rats aged 50 days were ovariectomized. At 70 days of age, 12 rats were treated with BPE 500 mg/kgBB and 1000mg/kgBB, 5 rats were treated with estradiol 2g/day while others served as control were treated with CMC-Na 0.5% and sacrificed 2 weeks later. The base line ovariectomized rats and base line non-ovariectomized rats were sacrificed at 70 days of age. The in silico experiment examined by molecular docking between myricetin and estrogen receptor alpha (ER-α). The result of in vivo experiment showed that 1000 mg/kgBW BPE induced c-Myc expression  and  enhance  ovariectomized  rat  mammary  gland  development  significantly. Meanwhile, molecular docking showed that there are hydrogen bond interaction between bioactive compound in BPE and Estrogen Receptor (ER)-α but less powerfull than estrogen and ER-α interaction. In summary, BPE can act as an estrogen agonist,  resulting in the enhancement of c-Myc expression. 

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