Anticancer Activity Studies of Self-nanoemulsifying Drug Delivery Systems (SNEDDS) Hibiscus sabdariffa L. as Cisplatin Co-Chemotherapy in T47D Breast Cancer Cells
DOI:
https://doi.org/10.24071/jpsc.v23i1.1079Keywords:
Antiproliferative, Combination Index, Hibiscus sabdariffa, SNEDDS, TNF αAbstract
Hibiscus sabdariffa L. (HS) exhibits strong anticancer activity, which can potentially treat breast cancer. A delivery system, namely self-nano-emulsifying drug delivery systems (SNEDDS), has been developed by our research group to carry the HS, indicating cytotoxicity against T47D breast cancer cells. To further evaluate the anticancer activity of HS SNEDDS, this study aimed to measure the anticancer activity of HS SNEDDS as a Cisplatin co-chemotherapy agent. The potential of HS SNEDDS as an anticancer agent was evaluated by measuring the anti-proliferation, combination index (CI), and immunocytochemistry of TNF-α gene expression. HS SNEDDS at a concentration of 241.990 µg/mL exhibited anti-proliferation properties against T47D cells with the highest doubling time, i.e., 9.4-fold compared to the control. The combination of HS SNEDDS and Cisplatin indicated a lowest CI of 0.17, showing the synergistic effect. Furthermore, combining HS SNEDDS and Cisplatin showed the highest TNF-α gene expression of 17,939 ± 7,323, indicating a better potency as a Cisplatin co-chemotherapy agent in T47D breast cancer cells compared to control and single administration. Based on these results, HS SNEDDS can be used as a co-chemotherapy agent for Cisplatin, which can increase the Cisplatin effect.
References
Akram, Hadeel Mazin; Haleem, Azhar M.; Salah, R., 2024. Antioxidant and Antineoplastic Activities of Hibiscus sabdariffa Linn. Petal Extracts against Oral Squamous Cell Carcinoma Cell Line. Oral Health and Preventive Dentistry, 22, 131–138.
Aldossary, S.A., 2019. Review on Pharmacology of Cisplatin: Clinical Use, Toxicity and Mechanism of Resistance of Cisplatin. Biomedical and Pharmacology Journal, 12(1), 7–15.
Anggi, V., Patala, R., Arfiah, A., Dewi, N.P., 2023. Anticancer Activity of Rosella Flowers (Hibiscus Sabdariffa l.) In HepG2 cells. Jurnal Penelitian Pendidikan IPA, 9(SpecialIssue), 698–703.
Azizi, E., Fouladdel, S., Movahhed, T.K., Modaresi, F., Barzegar, E., Ghahremani, M.H., Ostad, S.N., Atashpour, S., 2022. Quercetin Effects on Cell Cycle Arrest and Apoptosis and Doxorubicin Activity in T47D Cancer Stem Cells. Asian Pacific Journal of Cancer Prevention, 23(12), 4145–4154.
Bassong, T.R., Kenmogne, L.V., Awounfack, C.F., Ndinteh, D.T., Njamen, D., Zingue, S., 2022. Effects of Hibiscus sabdariffa Calyxes Aqueous Extract on Antioxidant Status and Histopathology in Mammary Tumor-Induced in Rats. Evidence-based Complementary and Alternative Medicine, 2022.
Chatran, M., Pilehvar-Soltanahmadi, Y., Dadashpour, M., Faramarzi, L., Rasouli, S., Jafari-Gharabaghlou, D., Asbaghi, N., Zarghami, N., 2018. Synergistic anti-proliferative effects of metformin and silibinin combination on T47D breast cancer cells via hTERT and cyclin D1 inhibition. Drug Research, 68(12), 710–716.
Chou, T.C., 2018. The combination index (CI < 1) as the definition of synergism and of synergy claims. Synergy, 7, 49–50.
Diaz Arguello, O.A., Haisma, H.J., 2021. Apoptosis-inducing tnf superfamily ligands for cancer therapy. Cancers, 13(7).
Dona, R., Sulistyani, N., Nurani, L.H., 2016. Uji sitotoksisitas dan antiproliferatif ekstrak etanol daun leunca (Solanum Nigrum,L) terhadap sel raji. Pharmaciana, 6(2), 181–190.
Edityaningrum, C.A., Khairurrizki, A., Nurani, L.H., Bachri, M.S., Yuliani, S., Utami, D., 2024. Co-Chemotherapy Effect ofTheExtract of Hibiscus Sabdariffaand Cisplatin Against Apoptosis and Anti-Proliferation on T47d and Vero Cells. Tropical Journal of Natural Product Research, 8(June), 7509–7513.
Fiorentino, F.P., Bagella, L., Marchesi, I., 2018. A new parameter of growth inhibition for cell proliferation assays. Journal of Cellular Physiology, 233(5), 4106–4115.
Fithrotunnisa, Q., Arsianti, A., Kurniawan, G., Qorina, F., Tejaputri, N.A., Azizah, N.N., 2020. In vitro cytotoxicity of Hibiscus sabdariffa Linn extracts on A549 lung cancer cell line. Pharmacognosy Journal, 12(1), 14–19.
Hamza, A.A., Heeba, G.H., Hassanin, S.O., Elwy, H.M., Bekhit, A.A., Amin, A., 2023. Hibiscus-cisplatin combination treatment decreases liver toxicity in rats while increasing toxicity in lung cancer cells via oxidative stress- apoptosis pathway. Biomedicine and Pharmacotherapy, 165(July).
Haryanti, S., Sholikhah, I.Y.M., Widiyastuti, Y., 2019. Efek Sinergis Kombinasi Ekstrak Etanolik Kayu Secang dan Rimpang Lempuyang pada Sel Kanker Payudara MCF-7. Jurnal Kefarmasian Indonesia, 9(1), 1–9.
Hasibuan, P.A.Z., Sumaiyah, S., 2019. The anti-proliferative and pro-apoptotic properties of Ethanol Plectranthus amboinicus (Lour.) Spreng. Leaves ethanolic extract nanoparticles on T47D cell lines. Asian Pacific Journal of Cancer Prevention, 20(3), 897–901.
Hassan, S.T.S., Berchová, K., Šudomová, M., 2016. Antimicrobial, antiparasitic and anticancer properties of Hibiscus sabdariffa (L.) and its phytochemicals: In vitro and in vivo studies. Ceska a Slovenska Farmacie, 65(September), 10–14.
Imanuel, L.K., Sunarni, T., Herdwiani, W., 2021. Aktivitas sitotoksik dan ekspresi protein p53 dan bcl-2 ekstrak dan fraksi daun yakon (Smallanthus sonchifolius) terhadap sel kanker T47D. JPSCR: Journal of Pharmaceutical Science and Clinical Research, 6(1), 74.
Kashif, M., Andersson, C., Hassan, S., Karlsson, H., Senkowski, W., Fryknäs, M., Nygren, P., Larsson, R., Gustafsson, M.G., 2015. In vitro discovery of promising anti-cancer drug combinations using iterative maximisation of a therapeutic index. Scientific Reports, 5(August), 1–13.
Laskar, Y.B., Mazumder, P.B., 2020. Insight into the molecular evidence supporting the remarkable chemotherapeutic potential of Hibiscus sabdariffa L. Biomedicine and Pharmacotherapy, 127(April), 110153.
Malacrida, A., Erriquez, J., Hashemi, M., Rodriguez-Menendez, V., Cassetti, A., Cavaletti, G., Miloso, M., 2022. Evaluation of antitumoral effect of Hibiscus sabdariffa extract on human breast cancer cells. Biochemistry and Biophysics Reports, 32(September), 101353.
Mohamad, S.H., 2016. Tumor Necrosis Factor-Alpha (TNF-a) Expression in Mice Infected with Aspergillus Fumigatus Using Immunohistochemichal Technique. International Journal of Science, 25(1), 183–189.
Niu, J., Li, M., Wang, Y., 2024. Cell Proliferation and Cytotoxicity Assays , The Fundamentals for Drug Discovery. Drug Discovery and Pharmacology (IJDDP), 3(3).
Nolan, E., Lindeman, G.J., Visvader, J.E., 2023. Deciphering breast cancer: from biology to the clinic. Cell, 186(8), 1708–1728.
Nurani, L.H., 2011. Ekspresi COX-2 Sel Kanker Payudara T47D Oleh Pengaruh Fraksi Etil Asetat Ekstrak Etanol Akar Pasak Bumi ( Eurycoma Longifolia , Jack ). Universitas Ahmad Dahlan, 55–60.
Paraíso, C.M., Siqueira, S., Yara, C., Ogawa, L., Sato, F., 2020. Hibiscus sabdariffa L . extract : Characterization ( FTIR ‑ ATR ), storage stability and food application. Emirates Journal of Food and Agriculture, 32(1), 55–61.
Trayes, K.P., Cokenakes, S.E.H.., 2021. Breast cancer treatment. American Family Physician, 104(2), 171–178.
Tsai, Tsung-Chang; Huang, Hui-Pei; Chang, K.-T. et al., 2016. Anthocyanins from Roselle Extract Arrest Cell Cycle G2/M Phase Transition via ATM/Chk Pathway in p53-deficient Leukemia HL-60 Cells. Environmental Toxicology,.
Wang, B., Sun, T., Zhao, Y., Wang, S., Zhang, J., Wang, Z., Teng, Y.E., Cai, L., Yan, M., Wang, X., Jiang, Z., Pan, Y., Luo, J., Shao, Z., Wu, J., Guo, X., Hu, X., 2022. A randomized phase 3 trial of Gemcitabine or Nab-paclitaxel combined with cisPlatin as first-line treatment in patients with metastatic triple-negative breast cancer. Nature Communications, 13(1).
Wu, C.H., Huang, C.C., Hung, C.H., Yao, F.Y., Wang, C.J., Chang, Y.C., 2016. Delphinidin-rich extracts of Hibiscus sabdariffa L. trigger mitochondria-derived autophagy and necrosis through reactive oxygen species in human breast cancer cells. Journal of Functional Foods, 25, 279–290.
Yasmin, R., Gogoi, S., Bora, J., Chakraborty, A., Dey, S., Ghaziri, G., Bhattacharjee, S., Singh, L.H., 2023. Novel Insight into the Cellular and Molecular Signalling Pathways on Cancer Preventing Effects of Hibiscus sabdariffa : A Review . Journal of Cancer Prevention, 28(3), 77–92.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Jurnal Farmasi Sains dan Komunitas (Journal of Pharmaceutical Sciences and Community)

This work is licensed under a Creative Commons Attribution 4.0 International License.

