Adam Hermawan
Cancer Chemoprevention Research Center Fakultas Farmasi, Universitas Gadjah Mada, Yogyakarta.
Articles
16
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

INDUKSI APOPTOSIS EKSTRAK ETANOL CIPLUKAN (Physalis angulata L.) PADA SEL KANKER LEHER RAHIM HeLa MELALUI PENEKANAN EKSPRESI Bel-2

Jurnal Bahan Alam Indonesia Vol 7, No 7 (2011)
Publisher : Indonesian Research Gateway

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Abstract

The incidence of cervical cancer continue to rise encourage a variety of studies to explore the plant as chemopreventive. Ciplukan (Physalis angulata L.) is one of potential plant as chemopreventive agent by regulating cell proliferation, cell cycle and apoptosis. In this study the potential effect of ciplukan ethanolic extract as inducers of apoptosis in human cervical carcinoma HeLa cell line wil be futher investigated. Induction of apoptosis was evaluated by Double Staining methods and Immunocytochemistry. Apoptosis observations qualitatively indicate the occurrence of early apoptosis marked by orange fluorescence and apoptosis bodies because of cell fragmentation. Then the expression of Bcl-2 was observed to know molecular mechanism of apoptosis. Immunocytochemistry experiment showed that Bcl-2 as antiapoptosis protein was inhibited in comparison with control cells. These data indicated that ciplukan ethanolic extract (P.angulata L.) could induced the apoptosis Hela cell line by downregulation of Bcl-2. Study of ciplukan shoud be developed to support ciplukan to be effective anticancer agents.

Structure Modification of Ethyl p-methoxycinnamate Isolated from Kaempferia galanga Linn. and Citotoxicity Assay of The Products on WiDr Cells

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

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Abstract

Ethyl p-methoxycinnamate, major ingredient of Kaempferia galanga rhizome, have been reported not only has analgesic – anti inflammatory activities like NSAIDs which inhibited cyclooxygenase, but also inhibit tumor cell proliferation in specimen of mouse epidermis. Therefore, it will be interesting to carry out  synthetic studies on the derivates of ethyl  p-methoxycinnamate and searching their citotoxic activity on WiDr cell. We wish to report of structure modification on carboxyl moiety of  ethyl p-methoxycinnamate  and  evaluation on their citotoxic activity  on WiDr cell. Isolation of ethyl p-methoxycinnamate from Kaempferia galanga rhizome was carried out by percolation with ethanol 96% as solvent. Hydrolysis of ethyl p-methoxycinnamate in basic condition was performed to obtain p-methoxycinnamic acid. Preparation of some thiourea derivates of ethyl  p-methoxycinnamate was carried out  by microwave irradiation. Citotoxicity assay was carried out by MTT method for 48 h.   Modification  of  carboxyl  group  of  ethyl  p-methoxycinnamate to its thiourea form could be carried out by microwave irradiation gave; (E)-3-(4-methoxyphenyl)-N-(phenylcarba- mothioyl)acrylamide (50%); (E)-3-(4-methoxyphenyl)-N-(4-methoxyphenylcarbamothi- oyl)acrylamide (26%) and (E)-3-(4-methoxyphenyl)-N-(4-methylphenylcarbamothioyl) acrylamide (54%), yield calculated for 2 step from the acid chloride. All compounds showed no citotoxic effect on WiDr cell at 48 h incubation.

SynergisticCombinationofCiplukan(Physalis angulata) HerbsEthanolicExtractandDoxorubicinonT47DBreast CancerCells

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

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Abstract

Doxorubicinisoneofchemotherapeuticagentwidelyusedinbreastcancertreatment,but in high dose doxorubicin gives negative side effect, including vomit, nausea, immune suppression, and cardiac toxicity. This toxicity hopefully could be reduced by combination chemotherapy using natural herbs such as ciplukan herb. This research was conducted to explorecytotoxicactivityofsingleciplukanherbsethanolicextractanditscombinationwith doxorubicinonT47Dbreastcancercells.Cytotoxicactivityofciplukanherbsethanolicextract only and its combination with doxorubicinwere tested on T47D cells using MTT assay toobtainIC50valueandcombinationindex(CI),respectively.Singleextractshowedcytotoxic activityonT47DcellswithIC50valueofwas160*g/ml.Thus,combinationtreatmentfrom ciplukanherbsethanolicextractanddoxorubicinshowedsynergisticeffect(CI<1,0).Thiseffect wasreachedatconcentrationofciplukanherbsethanolicextract-doxorubicin80μg/ml-2nM, 80 μg/ml-4 nM, and 80 μg/ml-8 nM. This research indicated that ciplukan herbs ethanolic extractispotentialtobeappliedasco-chemotherapeuticagentinbreastcancertherapy.

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.

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. 

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

The Cytotoxic Activity of Solanum Nigrum Ethanolic Extract on Widr Human Colon Cancer Cells

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

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Abstract

Solanum  nigrum  L.  or  Leunca  in  Indonesia  has  been  traditionally  used  as  a  herbal plant,  which  is  believed  to  have  anti-tumor  properties,  although  the  mechanism  for  the activity  remains  unknown.  The  resecarch  aim  to  examine  the  cytotoxic  effect  of  the ethanolic extract of Solanum nigrum on WiDr human colon cancer cells. In this study, we prepared an ethanol extract from herb of Solanum nigrum and investigated the mechanism involved  in  its  growth-inhibitory  effect  on  WiDr  human  colon  cancer  cells.  Herbs  of Solanum nigrum dry powder is extracted with 70% ethanol then added into the WiDr cell culture  in  96  wells  plate  in  various  concentration  :  50,  100,  250,  and  500  µg/ml. Cytotoxicity  of  the  Solanum  nigrum  ethanolic  extract    was  analyzed  with  MTT  assay  on WiDr human colon cancer cell lines. Results from the MTT assay showed WiDr cells was weakly  suppressed  in  the  presence of  the  extract.  The  result  of  the  assay  also  showed a very  close  correlation  between  the  Solanum  nigrum  extract  concentration  and  the surviving  cell  numbers  which  means  the  extract  caused  cell  death  in  a  dose-dependent fashion  in  WiDr  cancer  cells  with  the  IC50  of  359,23  µg/ml.  Collectively,  the  research suggest  further  studies  to  explore  other  chemopreventive possibilites  of  Solanum  nigrum ethanolic extract.Key words : colon cancer, MTT assay, cytotoxic, WiDr, Solanum nigrum

Combination of Tangeretin and 5-Fluorouracil Modulates Cell Cycle and Induce Apoptosis on Widr Cells

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

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Abstract

Co-chemotherapeutics approaches are increasing in cancer treatment in order mainly to suppress the resistance phenomenon of cancer treatment and to enhance the cytotoxic effect of the main chemotherapeutics agent. Tangeretin has been known to have cytotoxic effect to some cancer cells through some pathways in the cells. To explore the potential effect of tangeretin as co-chemotherapeutics agent this research was subjected to study the cytotoxic  effect of tangeretin in combination with 5-Fluoro Uracil (5-FU) on WiDR colon cancer cells covering the modulation of cell cycle and apoptosis induction. Cytotoxic effect was examined by using MTT assay while apoptosis induction was determined by annexin-V flowcytometry. Under MTT assay, tangeretin showed weak cytotoxic activity on the cells. However, tangeretin significantly enhanced the cytotoxic effect of 5-FU on the cells. This co-chemotherapeutics effect likely correlated with cell cycle modulation effect, especially in inducing polyploidy phenomenon as expressed in the flowcytometric graph of the DNA content. This combination also increased apoptosis induction. These result suggest that tangeretin is potential to be developed as co-chemotherapeutic agent for 5-FU on colon cancer and further molecular mechanism need to be exploredKeywords : Tangeretin, 5-Fluorourasil, WiDr, cell cycle, apoptosis

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