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All Journal Indonesian Journal of Cancer Chemoprevention Journal of Mathematical and Fundamental Sciences Indonesian Journal of Biotechnology Majalah Obat Tradisional Journal of Tropical Biodiversity and Biotechnology INDONESIAN JOURNAL OF PHARMACY The Indonesian Biomedical Journal JURNAL MANAJEMEN DAN PELAYANAN FARMASI (Journal of Management and Pharmacy Practice) JFIOnline Jurnal Ilmu Kefarmasian Indonesia Majalah Kesehatan Pharmamedika
Muthi Ikawati
Faculty Of Pharmacy, Universitas Gadjah Mada
Agriculture, Biological Sciences & Forestry Astronomy Biochemistry, Genetics & Molecular Biology Chemistry Earth & Planetary Sciences Environmental Science Health Professions Immunology & microbiology Materials Science & Nanotechnology Mathematics Medicine & Pharmacology Physics Public Health

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Chromolaena odorata L. Leaf Extract Elevates Cytotoxicity of Doxorubicin on 4T1 Breast Cancer Cells Putri, Amaliya Permata; Rahmawati, Desty Restia; Rahman, Faaza Aulia; Meiyanto, Edy; Ikawati, Muthi
Indonesian Journal of Cancer Chemoprevention Vol 14, No 3 (2023)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev14iss3pp160-170

Abstract

Chemotherapeutic agents for breast cancer such as doxorubicin can attack normal cells as the side effects. Chromolaena odorata L. and its chemical content, sinensetin, have potential anticancer  and  antioxidant  properties.  The  objective  of  this  research  is  to  examine  the anticancer properties of C. odorata leaves extract and sinensetin on 4T1 triple negative breast cancer (TNBC) cells combined with doxorubicin. The MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5 diphenyltetrazolium  bromide)  assay  on  4T1  cells  was  used  to  determine  the  IC50 and the Combination  Index  (CI)  of  the  two  agents  in  combination.  Washing  out the  treatment  and determining  the  cells  viability  after  a  few  days  was done  to evaluate  the  persistence  of the  effects  to  cancer  cells.  Chromolaena odorata  extract  (COE)  obtained  was  proven  to contain  sinensetin  which  gave  a positive  signal  on  the  chromatogram.  COE  and  sinensetin were  moderately  cytotoxic  to  4T1  cells  with  IC50  value  of  53  μg/mL  and  58  μM  (21.6 μg/mL), respectively. Both compounds were synergist (CI<0.7) to strong synergist (CI<0.3) when combined with doxorubicin (IC50 90 nM = 0.05 μg/mL). COE and sinensetin exhibited moderate and not cytotoxic against Vero cells with IC50 values of 60 μg/mL and 243 μM (90.43 μg/mL), respectively. Both COE and sinensetin showed selectivity index values of >1 (1.13 and 4.19, respectively).  Moreover,  the  cytotoxic  effects  of  COE  on  4T1  cells  was  persisted  until  48  h after  removing  COE  from  the  medium,  indicating  the  tumor-suppression  potency  of  COE. Our findings strengthen the scientific basis of C. odorata leaves extract to be developed as a co-chemotherapeutics agent for doxorubicin on TNBC.Keywords: Chromolaena odorata L., breast cancer cells, doxorubicin, co-chemotherapy, kidney cells.
Citrus Flavonoids from Citrus reticulata Peels Potentially Target an Autophagy Modulator, MAP1LC3A, in Breast Cancer Anggoro, Bayu; Kumara, Dennaya; Angelina, Dhella; Ikawati, Muthi
Indonesian Journal of Cancer Chemoprevention Vol 12, No 3 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev12iss3pp114-122

Abstract

Citrus flavonoids have been known for their vast biological activities including chemoprevention activities. However, the organic solvent extraction system limits its potential utilization. We recently adopted a hydrodynamic-cavitation method to extract citrus flavonoids from citrus peels. In this study we verified the high flavonoid content of the hydrodynamic-cavitation extract from Citrus reticulata peels and explore the potency of its citrus flavonoid contents as targeted chemoprevention agent for breast cancer by using bioinformatics. Based on a thin layer chromatography, the extract positively yielded high content of citrus flavonoids represented by hesperidin. The toxicity analysis by Protox II Online Tool revealed that hesperidin as the major citrus flavonoid in the extract was considered safe with a predicted LD50 of 12,000 mg/kg. We then further exploring citrus flavonoids’ capacity in targeting MAP1LC3A, a key protein in autophagy. UALCAN analysis validated that low expression of MAP1LC3A is associated with low survival rates in breast cancer patients. Limonin, hesperidin, narirutin, neohesperidine, and naringin are flavonoids from citrus peels that predicted to have inhibitory activity against Protein Kinase A (PKA), a negative upstream of MAP1LC3A, calculated by KNIME. Citrus flavonoids scoparone, cirsimaritin, 4',5,7-trimethoxyflavone, eupatorine, and hesperidin were also exhibit similar structure to an agonist of ATG4B, a protein that plays a role in MAP1LC3A activation. Furthermore, eupatorine, hesperidin, and cirsimaritin displayed a high affinity to ATG4B based on a molecular docking. We concluded that citrus flavonoids from citrus peels are safe to normal cells, and the citrus flavonoids potentially targets MAP1LC3A by inhibiting PKA and acting as ATG4B agonists. Thus, this extract-contained flavonoids from citrus peels is potential to be investigated further as a chemoprevention agent by inducing autophagy, especially for breast cancer.Keywords: Citrus reticulata, citrus flavonoid, autophagy, MAP1LC3A, breast cancer.
The Extract of Merremia mammosa Tubers Increases the Cytotoxicity of Doxorubicin and Induces Apoptosis in 4T1 Malignant Cancer Cells Aulia Nur Septiani; Fatiha Citra Effendi; Nadya Rianasari; Muhammad Yusuf Alfaqih; Afifah Nisa Al Qisthy; Edy Meiyanto; Muthi Ikawati
Indonesian Journal of Cancer Chemoprevention Vol 16, No 1 (2025)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev16iss1pp57-66

Abstract

Doxorubicin has been incorporated in cancer therapy regimes for wide-range malignancies, but it causes many side effects. These adverse effects can be overcome by combining doxorubicin with other ingredients that possess anticancer potential but are safe on normal cells. The tubers of Merremia mammosa, locally known as “Bidara Upas” in Indonesia, have been proven to have anticancer potential with resin glycosides as the active compounds. This research aims to develop the extract of M. mammosa’s tubers (MTE) as a co-chemotherapy agent for doxorubicin. A malignant cancer cell line, 4T1, was used as the model. MTE was obtained by maceration in 96% ethanol. The thin layer chromatography confirmed that MTE contains glycoside compounds. Administration of MTE to 4T1 cells showed cytotoxic activity with an IC50 value of 61 μg/mL as evaluated by MTT assay. The combination of MTE and doxorubicin exhibited synergistic cytotoxic effects with a combination index of <0.7. Moreover, MTE at around IC50 was able to cause DNA fragmentation indicating apoptosis as observed by the agarose gel electrophoresis.These data support our hypothesis that MTE may serve as a potential co-chemotherapeutic agent for doxorubicin; however, the apoptosis-inducing potency of the combination requires further investigation.Keywords: 4T1 cell, apoptosis, Bidara Upas, co-chemotherapy.
Co-Authors . Anindyajati Abdul Manaf Ali, Abdul Manaf Adam Hermawan ADTYA FITRIASARI Afifah Nisa Al Qisthy Afifah, Anis Afivah Dewi Anggraeni Agusta Fauzi, Ilham Alfi Yasmina Angelina, Dhella Anggoro, Bayu Anindyajati Anindyajati ANINDYAJATI ANINDYAJATI ANNISA KARAMITA Annisa Khumaira Astrid Ayu Maruti Astrid Ayu Maruti Aulia Nur Septiani Chio Oka, Chio Dewi Pratiwi Dewi Pratiwi Dhania Novitasari Dhiya Ulhaq Salsabila Dyaningtyas D.P. Putri Dyaningtyas Dewi Putri Pamungkas EDIATI EDIATI Ediati Sasmito Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto EDY MEIYANTO Edy Meiyanto Edy Meiyanto Edy Meiyanto Een Sri Endah Endah Puji Septisetyani Endah Puji Septisetyani, Endah Puji Erlina Rivanti Erlina Rivanti Fatiha Citra Effendi Fikri Amalia Gono, Christina Mutiara Putri Hanifa, Mila Hapsari, Novia Permata Hilyatul Fadliyah Ibrahim Arifin Ika Putri Nurhayati Ilham Augusta F Ilham Augusta F. Imaniyyati, Niar Nurul Inna Armandari Inna Armandari Jenie, Riris Istighfari Jun-Ya Kato Jun-ya Kato Kumara, Dennaya Mintarsih, Betty Mintarsih, Betty Mitsunori Kirihata Moordiani Moordiani Muhammad Novrizal Abdi Sahid Muhammad Yusuf Alfaqih Mustofa Mustofa Nadya Rianasari Nanda Resa Pratama Nanda Resa Pratama Natasia, Nyssa Niken Nur W Niken Nur W, Niken Nindya Budiana Putri Normaidah, Normaidah Novi Hastuti Novi Hastuti, Novi Nurma Sabila Nurramadhani A. Sida Purwanto, Heri Putri, Amaliya Permata Rahman, Faaza Aulia Rahmani, Mawardi Rahmani, Mawardi Rahmawati, Desty Restia Ratih Hardika Pratama RATIH HARDIKA PRATAMA Ratih Hardika Pratama Ratna Asmah Susidarti Ratna Asmah Susidarti Ratna Asmah Susidarti Rhamandana, I Made Rifai, Fauziah Novita Putri RIRIS ISTIGHFARI JENIE Rita Riata Rita Riata Ritmaleni, Ritmaleni Rohmad Yudi Utomo Sagiyo, Marrita Langgeng Sari Haryanti Sari Haryanti Shirly Kumala Sismindari, Sismindari Sri Handayani Sri Kasianningsih Sri Kasianningsih Sri Pudjiraharti Sukari, Mohd. Aspollah Sukari, Mohd. Aspollah Susi Ari Kristina Susi Ari Kristina Susi Ari Kristina Syifa Athia Zainun Faqiha Tafrihani, Ahmad Syauqy Wardani, Ratih Kurnia Wulandari Wulandari Wulandari, Febri Yogi Ertanto Yogi Ertanto Yohanes, Jasson Yurista Gilang Yurista Gilang YURISTA GILANG IKHTIARSYAH Ziana Walidah Zulfin, Ummi Maryam