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All Journal Farmasains : Jurnal Farmasi dan Ilmu Kesehatan Indonesian Journal of Cancer Chemoprevention
Aditya Fitriasari
Fakultas Farmasi Universitas Gadjah Mada
Biochemistry, Genetics & Molecular Biology Health Professions Immunology & microbiology Medicine & Pharmacology Public Health

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MCF-7 Resistant Doxorubicin are Characterized by Lamelapodia, Strong Adhesion on Substrate and P-gp Overexpression Putri, Dyaningtyas Dewi P.; Sarmoko, .; Febriansah, Rifki; Puspitasari, Endah; Ismiyati, Nur; Fitriasari, Aditya
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 Gilang, Yurista; Hermawan, Adam; Fitriasari, Aditya; Jenie, Riris Istighfari
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
EFEK SITOTOKSIK EKSTRAK ETANOLIK HERBA SELEDRI (Apium graveolens L.) PADA SEL KANKER T47D, WiDr, DAN HeLa Palupi, Kartika Dyah; Wulandari, Ainun; Goenadi, Fina Aryani; Nur, Kholid Alfan; Fitriasari, Aditya; Meiyanto, Edy
Farmasains : Jurnal Farmasi dan Ilmu Kesehatan Vol 1, No 2 (2011): Oktober 2010 - Maret 2011
Publisher : University of Muhammadiyah Malang

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (206.379 KB) | DOI: 10.22219/far.v1i2.1164

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.
The Doxorubicin-Induced G2/M Arrest in Breast Cancer Cells Modulated by Natural Compounds Naringenin and Hesperidin Junedi, Sendy; Hermawan, Adam; Fitriasari, Aditya; Setiawati, Agustina; Susidarti, Ratna Asmah; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 12, No 2 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev12iss2pp83-89

Abstract

Doxorubicin as the common drug for breast cancer has been widely proposed to use in combine with a natural compound in order to overcome its side effects such as cardiotoxicity and resistance. Previously, we reported that naringenin and hesperidin, the abundant flavanons in citrus fruit peel, increased cytotoxic and apoptosis activities of doxorubicin in doxorubicin resistant breast cancer cells (T47D and MCF-7 cells). Since doxorubicin arrests G2/M phase in most cancer cells, both flavanons are speculated to affect the similar phase in breast cancer cells. Cell cycle distributions were determined by flowcytometry using propidium iodide (PI) to stain DNA of the cells. Combination of naringenin or hesperidin with doxorubicin increased accumulation of T47D cells in G2/M phase, while in MCF-7 cells, accumulated cells in G2/M phase were decreased, accompanying with slightly increased in G1 phase. Naringenin itself had no effect on cell cycle of both cells. Whereas, hesperidin arrested G2/M and G1 phases in T47D and MCF-7 cells, respectively. The different effect of naringenin and hesperidin in T47D and MCF-7 cells is most likely caused by difference of p53 status. In p53 mutant, T47D cells, naringenin and hesperidin supported mechanism of doxorubicin to arrest at G2/M that to be considered via p53-independent pathway. Whereas, in p53 wild-type MCF-7 cells, naringenin and hesperidin decreased G2/M arrest, suggesting that both flavanons do not utilize cell cycle arrest for their anticancer activity with doxorucibin. This study revealed that potential co-chemoterapeutic agents, naringenin and hesperidin distinctly modulated cell cycle arrest induced by doxorubicin according to the characteristic of breast cancer cells.Keywords: naringenin, hesperidin, doxorubicin, cell cycle, breast cancer cells.
Co-Authors Adam Hermawan Agustina Setiawati Ainun Wulandari Dyaningtyas Dewi P. Putri Edy Meiyanto Endah Puspitasari Fina Aryani Goenadi, Fina Aryani Kartika Dyah Palupi Kholid Alfan Nur Nur Ismiyati Ratna Asmah Susidarti Rifki Febriansah Riris Istighfari Jenie Sarmoko Sarmoko Sendy Junedi Yurista Gilang