Abstract
Objective
It is well known that E. officinalis (Amla) has anti-oxidant, tonifying, anti-aging, detoxifying, and anti-cancer properties in addition to acting as a broad spectrum antibiotic against various infectious diseases. This wonder plant contains antioxidants which aid in the clearing of toxins from the body (The liver is where toxins are found in abundance) and may also protect the liver from the resulting damage. However, the effects of E.officinalis on normal human liver cells along with cancer human liver cells remain largely unknown. The purpose of this study is to look into the hapto-protective and anticancer effects of E. officinalis on normal as well as cancer liver cell line.
Methodology
approaching the same, aqueous extract of E. officinalis fruit extract was prepared for anticancer screening. The hepatoprotective and anticancer effect of amla on cell viability, cytotoxicity and cell proliferation of normal human liver cells (Wrl-68) and cancer human liver cell (HepG2) was analyzed using trypan blue dye exclusion test, MTT & WST assay as well as by fluorescent staining with PI & DAPI. ROS and Apoptosis was analyzed by DCFDA and Annexin V/PI assay and expression of apoptosis-regulating proteins was evaluated by immunoblotting.
Results
The study demonstrated that 50 μg/ml of fruit extract of E.officinalis inhibited cell viability and induced cytotoxicity, simultaneously triggers apoptosis in cancer cells by generation of intracellular ROS species in HepG2 cells without any toxic effect on normal liver cell after 48 h of incubation.
Conclusion
E.officinalis fruit shows tremendous pharmacological and medicinal application along with cheap or cost effective clinical validation for the treatment of both organ specific tumors as well as for various types of leukemia.
Similar content being viewed by others
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Code availability
Not applicable.
References
Palhares RM, Gonçalves Drummond M, Dos Santos Alves Figueiredo Brasil B, Pereira Cosenza G, das Graças Lins Brandão M, Oliveira G (2015) Medicinal plants recommended by the world health organization: DNA barcode identification associated with chemical analyzes guarantees their quality. PLoS ONE 10(5):e0127866. https://doi.org/10.1371/journal.pone.0127866
Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TP (2007) Indian herbs and herbal drugs used for the treatment of diabetes. J Clin Biochem Nutr 40(3):163–173. https://doi.org/10.3164/jcbn.40.163
Petrovska BB (2012) Historical review of medicinal plants’ usage. Pharmacogn Rev 6(11):1–5. https://doi.org/10.4103/0973-7847.95849
Nair A, Balasaravanan T, Jadhav S, Mohan V, Kumar C (2020) Harnessing the antibacterial activity of Quercus infectoria and Phyllanthus emblica against antibiotic-resistant Salmonella Typhi and Salmonella Enteritidis of poultry origin. Veterinary world 13(7):1388–1396. https://doi.org/10.14202/vetworld.2020.1388-1396
Thilakchand KR, Mathai RT, Simon P, Ravi RT, Baliga-Rao MP, Baliga MS (2013) Hepatoprotective properties of the Indian gooseberry (Emblica officinalis Gaertn): a review. Food Funct 4(10):1431–1441. https://doi.org/10.1039/c3fo60237k
Guo XH, Ni J, Xue JL, Wang X (2017) Phyllanthus emblica Linn. fruit extract potentiates the anticancer efficacy of mitomycin C and cisplatin and reduces their genotoxicity to normal cells in vitro. J Zhejiang Univ Sci 18(12):1031–1045. https://doi.org/10.1631/jzus.B1600542
Haque R, Bin-Hafeez B, Ahmad I, Parvez S, Pandey S, Raisuddin S (2001) Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice. Hum ExpToxicol 20(12):643–650. https://doi.org/10.1191/096032701718890568
Muthu PR, Bobby Z, Sankar P, Vickneshwaran V, Jacob SE (2018) Amla (Emblica officinalis) improves hepatic and renal oxidative stress and the inflammatory response in hypothyroid female wistar rats fed with a high-fat diet. J Basic Clin Physiol Pharmacol 29(2):175–184. https://doi.org/10.1515/jbcpp-2017-0116
Variya BC, Bakrania AK, Patel SS (2016) Emblica officinalis (Amla): A review for its phytochemistry, ethnomedicinal uses and medicinal potentials with respect to molecular mechanisms. Pharmacol Res 111:180–200. https://doi.org/10.1016/j.phrs.2016.06.013
Zhao T, Sun Q, Marques M, Witcher M (2015) Anticancer Properties of Phyllanthus emblica (Indian Gooseberry). Oxid Med Cell Longev. https://doi.org/10.1155/2015/950890
Khan MT, Lampronti I, Martello D, Bianchi N, Jabbar S, Choudhuri MS, Datta BK, Gambari R (2002) Identification of pyrogallol as an antiproliferative compound present in extracts from the medicinal plant Emblica officinalis: effects on in vitro cell growth of human tumor cell lines. Int J Oncol 21(1):187–192
Zhu X, Wang J, Ou Y, Han W, Li H (2013) Polyphenol extract of Phyllanthus emblica (PEEP) induces inhibition of cell proliferation and triggers apoptosis in cervical cancer cells. Eur J Med Res 18(1):46. https://doi.org/10.1186/2047-783X-18-46
De A, De A, Papasian C, Hentges S, Banerjee S, Haque I, Banerjee SK (2013) Emblica officinalis extract induces autophagy and inhibits human ovarian cancer cell proliferation, angiogenesis, growth of mouse xenograft tumors. PLoS ONE 8(8):e72748. https://doi.org/10.1371/journal.pone.0072748
Looi CY, Imanishi M, Takaki S, Sato M, Chiba N, Sasahara Y, Futaki S, Tsuchiya S, Kumaki S (2011) Octa-arginine mediated delivery of wild-type Lnk protein inhibits TPO-induced M-MOK megakaryoblastic leukemic cell growth by promoting apoptosis. PLoS ONE 6(8):e23640. https://doi.org/10.1371/journal.pone.0023640
Chaudhary A, Bhardwaj SK, Khan A, Srivastava A, Sinha KK, Ali M, Haque R (2023) Combinatorial effect of arsenic and herbal compounds in telomerase-mediated apoptosis induction in liver cancer. Biol Trace Elem Res 201(7):3300–3310. https://doi.org/10.1007/s12011-022-03430-0
Darvesh AS, Aggarwal BB, Bishayee A (2012) Curcumin and liver cancer: a review. Curr Pharm Biotechnol 13(1):218–228. https://doi.org/10.2174/138920112798868791
Romha G, Admasu B, HiwotGebrekidan T, Aleme H, Gebru G (2018) Antibacterial activities of five medicinal plants in ethiopia against some human and animal pathogens. Evid-based Complement Altern Med: eCAM. https://doi.org/10.1155/2018/2950758
Baliga MS, Dsouza JJ (2011) Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer. Eur J Cancer Prev 20(3):225–239. https://doi.org/10.1097/CEJ.0b013e32834473f4
Zhao T, Sun Q, Marques M, Witcher M (2015) Anticancer properties of Phyllanthus emblica (Indian Gooseberry). Oxid Med Cell Longev 2015:950890. https://doi.org/10.1155/2015/950890
Moon SC, Choi HJ, Chung TW, Lee JH, Lee SO, Jung MH, Kim BJ, Choi JY, Ha KT (2018) Sorbus commixta water extract induces apoptotic cell death via a ROS-dependent pathway. Oncol Lett 16(4):4193–4200. https://doi.org/10.3892/ol.2018.9217
Davies KJ (1999) The broad spectrum of responses to oxidants in proliferating cells: a new paradigm for oxidative stress. IUBMB Life 48(1):41–47. https://doi.org/10.1080/713803463
De A, De A, Papasian C, Hentges S, Banerjee S, Haque I, Banerjee SK (2013) Emblica officinalis extract induces autophagy and inhibits human ovarian cancer cell proliferation, angiogenesis, and growth of mouse xenograft tumors. PLoS ONE 8(8):e72748. https://doi.org/10.1371/journal.pone.0072748
Zaker A, Asili J, Abrishamchi P, Tayarani-Najaran Z, Mousavi SH (2017) Cytotoxic and apoptotic effects of root extract and tanshinones isolated from Perovskiaabrotanoides Kar. Iran J Basic Med Sci 20(12):1377–1384. https://doi.org/10.22038/IJBMS.2017.9568
Wang Q, Zhang L, Yuan X, Ou Y, Zhu X, Cheng Z, Zhang P, Wu X, Meng Y, Zhang L (2016) The relationship between the Bcl-2/Bax proteins and the mitochondria-mediated apoptosis pathway in the differentiation of adipose-derived stromal cells into neurons. PLoS ONE 11(10):e0163327. https://doi.org/10.1371/journal.pone.0163327
Acknowledgements
The work was funded by DST-SERB (Science and Engineering Research Board) India grant number EMR/2017/004171. Financial aid given to the first author by the Council for Scientific and Industrial Research (CSIR-UGC) in the form of a fellowship. The authors also like to thank the funding of researchers supporting Project number (RSPD2024R710) from King Saud University, Riyadh Saudi Arabia.
Author information
Authors and Affiliations
Contributions
The idea and layout of the research were helped by Rizwanul Haque. Archana Chaudhary prepared the material and collected the data. Formal analysis and investigation were carried out by Archana Chaudhary, and Rizwanul Haque. Nandani kumari helped in biochemical assay. Archana Chaudhary drafted the manuscript. Prof. Rizwanul Haque, Dr. Manish kumar, Dr. Md. Margoob Ahmad, Dr. Mohammad Shamsul Ola and all authors reviewed and edited previous version of manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
Archana Chaudhary, Nandani kumari, Manish kumar, Md. MargoobAhmad, Mohammad Shamsul Ola, Rizwanul Haque declare that we have no conflict of interest.
Ethical statement
This article does not contain any studies with human participants or animals performed by any of the authors.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Chaudhary, A., kumari, N., kumar, M. et al. Reactive oxygen species mediated apoptosis induction in human liver cancer cells by Emblica officinalis (Amla): a new trend in liver cancer treatment. Toxicol. Environ. Health Sci. (2024). https://doi.org/10.1007/s13530-024-00209-9
Accepted:
Published:
DOI: https://doi.org/10.1007/s13530-024-00209-9