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All Journal Indonesian Journal of Cancer Chemoprevention
Argandita Meiftasari
Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada
Biochemistry, Genetics & Molecular Biology Medicine & Pharmacology

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Red Betel Leaves Methanolic Extract (Piper crocatum Ruiz & Pav.) Increases Cytotoxic Effect of Doxorubicin on WiDr Colon Cancer Cells through Apoptosis Induction Nindi Wulandari; Argandita Meiftasari; Hilyatul Fadliyah; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 9, No 1 (2018)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev9iss1pp1-8

Abstract

Doxorubicin is a chemotherapeutic agent that causes a lot of side effects in high doses. Thus, combination with a co-chemotherapeutic agent which can increase its toxicity on cancer cells, is needed to reduce its therapeutic dose. Red betel leaves (Piper crocatum Ruiz & Pav.) have been known to contain flavonoids and alkaloids that have anticancer activity. This study was conducted to determine the cytotoxic effect and apoptosis induction of red betel leaves methanolic extract (RBM), doxorubicin (dox) and the combination of them on WiDr cells as model of colon cancer. RBM was extracted by soxhlet method using methanol. Cytotoxicity assay was performed using MTT assay for both single and combination treatments for 24 hours to determine IC50 and CI as their parameters. Apoptosis induction was analyzed by double staining method using ethidium bromide-acridine orange staining. Treatment of RBM and dox on WiDr cells for 24 hours showed cytotoxic activity with IC50 100 μg/mL and 1.6 μM respectively. Combination of RBM and dox performed synergism effect with CI<0.9 (p<0.05). Combination of RBM (12.5 μg/mL) and dox (0.4 μM) increased the number of apoptosis cells compared to each single treatment. Based on this study, it can be concluded that red betel leaves methanolic extract is potential to be developed as a co-chemotherapeutic agent of doxorubicin on colon cancer but still need further study to disclose the underlying molecular mechanisms.Keywords :  Red betel leaves (Piper crocatum Ruiz & Pav.), doxorubicin, WiDr cells, co- chemotherapeutic agent
Ethanolic Extract of Hedyotis corymbosa and Its Combination with 5-FU Inhibit Cyclin D Expression on WiDr Colorectal Cancer Cell Argandita Meiftasari; Januar Caesar W.P.; Annisa Novarina; Julika Yovi W.; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 7, No 1 (2016)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev7iss1pp25-30

Abstract

Hedyotis corymbosa has been used for long time as an important component in several folklore medicine formula to clinically treat various types of cancer, including colorectal cancer (CRC). Previously, Hedyotis corymbosa ethanolic extract (HEE) which contain ursolic acid reported to inhibit CRC growth via induction of cancer cell apop­tosis and blocked the cell cycle, preventing G1 to S progression where cyclin D highly espressed in this phase. 5-fluorouracil (5FU), the first line chemotherapy of colorectal cancer have had resistence and possessed several side effects such as neutropenia, immunosuppression, diarrhea, and also constipation. Therefore, the aim of this research is to conduct the antiproliferative effect and molecular analysis of HEE and its combination with 5FU. Molecular docking study was also done to approach the specific protein target of the compound. Antiproliferative effect was conducted by MTT assay, while cyclin D expression  was examined by immunofluorescence. The proliferative effect showed that both HEE and 5-FU had cytotoxic effect with IC50 value of 65 µg/mL and 90 µM respectively, meanwhile the combination of HEE and 5FU have synergism effect with CI = 0.48 on dose HEE = 22 µg/mL and 5FU= 6.25 µM. Immunofluorescence assay showed HEE and its combination with 5FU suppressed the expression of cyclin D. From molecular docking simulation, ursolic acid performed stable interaction with cyclin D. Our findings suggest that HEE may be an effective treat­ment for co-chemotherapic for 5-FU through inhibition of cyclin D expression.Keywords : Hedyotis corymbosa, 5-fluorouracil, colorectal cancer,  WiDr, cyclin D 
Co-Authors Annisa Novarina Hilyatul Fadliyah Januar Caesar W.P. Jenie, Riris Istighfari Julika Yovi W. Nindi Wulandari Riris Istighfari Jenie