The Cytotoxic Effects, Stimulation of p53, Caspase 3, and Bax by Potent Fractions Derived from the Leptastrea purpurea Sponge

Authors

  • Haryanto Susanto Doctoral Student, Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia
  • Nashi Widodo Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia
  • Masruri Masruri Department of Chemistry Department, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia.
  • Siti Mariah Ulfa Department of Chemistry Department, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia.
  • Nur Fitriana Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency, Bogor, Indonesia.
  • Rollando Rollando Pharmacy Department, Faculty of Health Sciences, Universitas Ma Chung, Malang, Indonesia.

DOI:

https://doi.org/10.26538/tjnpr/v8i6.19

Keywords:

Leptastrea purpurea, Bax, Caspase 5, P53, Cytotoxic

Abstract

Breast cancer remains a significant challenge in oncology, necessitating the exploration of novel therapeutic options. This study investigates the anticancer effects of ethanol and n-hexane fractions derived from the methanol extract of the Leptastrea purpurea sponge on T47D breast cancer cells. Employing cytotoxicity assays (MTT and WST-1), mitochondrial transmembrane potential assays, and protein expression analysis of p53, Caspase-3, and Bax, we aimed to elucidate the mechanisms underlying their potential anticancer activity. LC-MS/MS analysis was utilized to identify active compounds within the fractions. The results of the experiment demonstrate that the ethanol fraction exhibits significant efficacy against T47D breast cancer cells, with an IC50 value of 25.36 μg/mL indicating potent cytotoxicity. At a concentration of 1508 μg/mL, it induces cell death in 95% of T47D cells, highlighting its specificity in targeting breast cancer cells. Comparative analysis with cisplatin reveals a 9.92% higher rate of cell death induced by the ethanol fraction, suggesting superior apoptosis induction capability. Flow cytometry results show increased p53 expression at concentrations of 754 and 1508 μg/mL, with a concentration-dependent pattern. Furthermore, notable increases in Bax protein expression at concentrations of 377 and 754 μg/mL suggest the involvement of the ethanol fraction in regulating apoptosis. In conclusion, the ethanol fraction demonstrates promising potential as a cytotoxic and apoptosis-inducing agent for breast cancer therapy. These findings underscore the importance of exploring natural products from marine sources as potential anticancer agents.

Author Biography

Haryanto Susanto, Doctoral Student, Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia

Pharmacy Department, Faculty of Health Sciences, Universitas Ma Chung, Malang, Indonesia.

References

Rollando R, Monica E, Aftoni MH. In vitro Cytotoxic Potential of Sterculia quadrifida Leaf Extract Against Human Breast Cancer Cell Lines. Trop J Nat Prod Res. 2022 1;6(8):1228–32.

Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48.

Fitriana N, Rifa’i M, Masruri, Wicaksono ST, Nashi Widodo. Anticancer effects of Curcuma zedoaria (Berg.) Roscoe ethanol extract on a human breast cancer cell line. Chem Pap. 2023;77(1):399–411.

Zhang Z, Zhang H, Li D, Zhou X, Qin Q, Zhang Q. Caspase-3-mediated GSDME induced Pyroptosis in breast cancer cells through the ROS/JNK signalling pathway. J Cell Mol Med. 2021;25(17):8159–68.

Rollando R, Monica E, Afthoni MH, Warsito W, Masruri M, Widodo N. A Phenylpropanoid Compound from the Seeds of Sterculia quadrifida and its Cytotoxic Activity. Trop J Nat Prod Res. 2023;7(6):3203–8.

Rollando R, Warsito W, Masruri M, Widodo W. Sterculia foetida Leaf Fraction Against Matrix Metalloproteinase-9 Protein and 4T1 Breast Cancer Cells: In-Vitro and In-Silico Studies. Trop J Nat Prod Res. 2021;5(1):113–21.

Rollando R, Monica E, Afthoni MH, Warsito W, Masruri M, Widodo N, Zainul R. In-vitro and In-silico Studies of a Phenylpropanoid Compound Isolated from Sterculia quadrifida Seeds and Its Inhibitory Effect on Matrix Metalloproteinase-9: http://www.doi.org/10.26538/tjnpr/v7i7.30. Trop J Nat Prod Res. 2023;7(7):3490–5.

Hayes JD, Dinkova-Kostova AT, Tew KD. Oxidative Stress in Cancer. Cancer Cell. 2020;38(2):167–97.

Gulcin İ. Antioxidants and antioxidant methods: an updated overview. Arch Toxicol. 2020;94(3):651–715.

Hariono M, Rollando R, Karamoy J, Hariyono P, Atmono M, Djohan M, Wiwy W, Nuwarda R, Kurniawan C, Salin N, Wahab H. Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study. Mol Basel Switz. 2020;25(20).

Hariono M, Rollando R, Yoga I, Harjono A, Suryodanindro A, Yanuar M, Gonzaga T, Parabang Z, Hariyono P, Febriansah R, Hermawansyah A, Setyani W, Wahab H. Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study (Part II). Mol Basel Switz. 2021;26(5):1464.

Guney Eskiler G, Ozman Z, Haciefendi A, Cansaran-Duman D. Novel combination treatment of CDK 4/6 inhibitors with PARP inhibitors in triple negative breast cancer cells. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(5):1031–41.

Özerkan D. The Determination of Cisplatin and Luteolin Synergistic Effect on Colorectal Cancer Cell Apoptosis and Mitochondrial Dysfunction by Fluorescence Labelling. J Fluoresc. 2023;33(3):1217–25.

Rollando R, Yuniati Y, Monica E. Bioactive Potential of Cephalosporium sp. a Fungal Endophyte Isolated from Phyllanthus niruri L. Trop J Nat Prod Res. 2023;7(4):2749–55.

Liu Y, VanAernum Z, Zhang Y, Gao X, Vlad M, Feng B, Cross R, Kilgore B, Newman A, Wang D, Schuessler HA, Richardson DD, Chadwick JS. LC-MS Approach to Decipher a Light Chain Chromatographic Peak Splitting of a Monoclonal Antibody. Pharm Res. 2023;40(12):3087–98.

Hariono M, Nuwarda RF, Yusuf M, Rollando R, Jenie RI, Al-Najjar B, Julianus J, Putra KC, Nugroho ES, Wisnumurti YK, Dewa SP, Jati BW, Tiara R, Ramadani RD, Qodria L, Wahab HA. Arylamide as Potential Selective Inhibitor for Matrix Metalloproteinase 9 (MMP9): Design, Synthesis, Biological Evaluation, and Molecular Modeling. J Chem Inf Model. 2020;60(1):349–59.

Dunavári EK, Kőházy A, Vecsernyés M, Szalma J, Lovász BV, Berta G, Lempel E. Does Preheating Influence the Cytotoxic Potential of Dental Resin Composites? Polymers. 2024;16(2):174.

Xu W, Shi D, Chen K, Palmer J, Popovich DG. An improved MTT colorimetric method for rapid viable bacteria counting. J Microbiol Methods. 2023;214:106830.

Li Y, Zhang T, Song Q, Gao D, Li Y, Jie H, Huang P, Zheng G, Yang J, He J. Cisplatin ototoxicity mechanism and antagonistic intervention strategy: a scope review. Front Cell Neurosci. 2023;17:1197051.

Spurlock B, Hanumanthu VS, Mitra K. Strategy of Isolating ‘Primed’ Tumor Initiating Cells Based on Mitochondrial Transmembrane Potential. Bio-Protoc. 2021;11(5):e3945.

Margineantu DH, Gregory Cox W, Sundell L, Sherwood SW, Beechem JM, Capaldi RA. Cell cycle dependent morphology changes and associated mitochondrial DNA redistribution in mitochondria of human cell lines. Mitochondrion. 2002;1(5):425–35.

Guefack MGF, Talukdar D, Mukherjee R, Guha S, Mitra D, Saha D, Das G, Damen F, Kuete V, Murmu N. Hypericum roeperianum bark extract suppresses breast cancer proliferation via induction of apoptosis, downregulation of PI3K/Akt/mTOR signaling cascade and reversal of EMT. J Ethnopharmacol. 2024;319(Pt 1):117093.

Li ZF, Feng JK, Zhao XC, Liu W, Gu SA, Li R, Lu YL, Mao RJ, Xia LL, Dong LL, Zhang LW, Ruan JY, Liu J, Li GF, Li T, Sun R, Qiu SL, Zheng ZZ, Dong T. The Extract of Pinellia Ternata-Induced Apoptosis of Leukemia Cells by Regulating the Expression of Bax, Bcl-2 and Caspase-3 Protein Expression in Mice. Transplant Proc. 2023;55(9):2232–40.

Wu Y, Li Z, Wedn AM, Casey AN, Brown D, Rao SV, Omarjee S, Hooda J, Carroll JS, Gertz J, Atkinson JM, Lee AV, Oesterreich S. FOXA1 Reprogramming Dictates Retinoid X Receptor Response in ESR1-Mutant Breast Cancer. Mol Cancer Res. 2023;21(6):591–604.

Yusuf H, Novia H, Fahriani M. Cytotoxic activity of ethyl acetate extract of Chromolaena odorata on MCF7 and T47D breast cancer cells. Narra J. 2023;3(3):e326.

Rollando R. Combination of Hedyotis corymbosa l. and Tinospora crispa ethanol extract increase cisplatin cytotoxicity on t47d breast cancer cells. Asian J Pharm Clin Res. 2018;171–7.

Rollando R, Warsito W, Masruri M, Widodo W. Pterygota alata (Roxb.) R.Br. Bark Fraction Induced Intrinsic Apoptotic Pathway in 4T1 Cells by Decreasing Bcl-2 and Inducing Bax Expression. Pak J Biol Sci. 2021;24(2):172–81.

Quarato G, Mari L, Barrows NJ, Yang M, Ruehl S, Chen MJ, Guy CS, Low J, Chen T, Green DR. Mitophagy restricts BAX/BAK-independent, Parkin-mediated apoptosis. Sci Adv. 2023;9(21):eadg8156.

An S, Yan S, Zhang Y, Xu H, Gan T, Liu Q. Is It Possible to Establish a Tumor-Suppressive Microenvironment With Glycine and Valine Supplement? Cancer Control J Moffitt Cancer Cent. 2020;27(1):1073274820954453.

Ntungwe E, Domínguez-Martín EM, Teodósio C, Teixidó-Trujillo S, Armas Capote N, Saraiva L, Díaz-Lanza AM, Duarte N, Rijo P. Preliminary Biological Activity Screening of Plectranthus spp. Extracts for the Search of Anticancer Lead Molecules. Pharmaceuticals. 2021;14(5):402.

Gao S, Tan H, Gang J. Inhibition of hepatocellular carcinoma cell proliferation through regulation of the cell cycle, AGE RAGE, and leptin signaling pathways by a compound formulation comprised of andrographolide, wogonin, and oroxylin a derived from Andrographis Paniculata(Burm.f.) Nees. J Ethnopharmacol. 2024;118001.

Shun MC, Yu W, Gapor A, Parsons R, Atkinson J, Sanders BG, Kline K. Pro-apoptotic mechanisms of action of a novel vitamin E analog (alpha-TEA) and a naturally occurring form of vitamin E (delta-tocotrienol) in MDA-MB-435 human breast cancer cells. Nutr Cancer. 2004;48(1):95–105.

Yang L, Yuan J, Liu L, Shi C, Wang L, Tian F, Liu F, Wang H, Shao C, Zhang Q, Chen Z, Qin W, Wen W. α-linolenic acid inhibits human renal cell carcinoma cell proliferation through PPAR-γ activation and COX-2 inhibition. Oncol Lett. 2013;6(1):197–202.

Downloads

Published

2024-06-29

How to Cite

Susanto, H., Widodo, N., Masruri, M., Ulfa, S. M., Fitriana, N., & Rollando, R. (2024). The Cytotoxic Effects, Stimulation of p53, Caspase 3, and Bax by Potent Fractions Derived from the Leptastrea purpurea Sponge. Tropical Journal of Natural Product Research (TJNPR), 8(6), 7459–7465. https://doi.org/10.26538/tjnpr/v8i6.19

Most read articles by the same author(s)

1 2 > >>