Skip to main content

Advertisement

SpringerLink
Log in

Evaluating the efficacy of an innovative herbal formulation (HF6) on different human cancer cell lines

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Cancer is reported to be the leading cause of death and illness worldwide. This research aims to evaluate the phytochemicals, antioxidant, cytotoxic, and apoptotic activities of the polyherbal formulation HF6. HF6 was prepared by blending equal quantities of plants powder, namely, Curcuma longa, Salvia officinalis, Cinnamomum zeylanicum, Capsicum annuum, Zingiber officinale, and Syzygium aromaticum, and later extracted using hexane (HF6H), chloroform (HF6C), ethyl acetate (HF6E), and methanol (HF6M) in Soxhlet apparatus. Among the four different extracts, only the hexane extract (HF6H) was significantly effective. The HF6H extract showed antioxidant and anticancer potentials against different cancer cell lines, and moderate cytotoxicity against non-cancer cells, rendering it a promising remedy. In addition, it exerted tremendous cytotoxic effects on MCF-7, Huh-7, HCT116, MDA-MB-231, LoVo, and HepG2 cells with IC50 values of 2.02, 4.5, 6.9, 11.4, 23.5, and 34.7 µg/mL, respectively. The morphological hallmarks of apoptosis such as the rounding of cells, loss of contact with neighboring cells, formation of cell membrane blebbing, and microspike protrusion were detected using several different techniques. DAPI staining revealed apoptotic nuclear morphology such as condensation and DNA fragmentation. The morphological changes of MCF7 cells were also analyzed by AO/EB fluorescence staining. MCF7-stained green cells were viable cells, whereas the treated cells showed fragmented green nuclei representing early apoptosis. The phytochemical screening of HF6H showed positive results regarding the presence of alkaloids, polyphenols, flavonoids, and sterols. The GC–MS (gas chromatography–mass spectrometry) analysis of the HF6H extract indicated the presence of 12 compounds, mainly trans-caryophyllene (21.55%), cis-isoeugenol (18.42%), acetyleugenol (17.53%), alpha farnesene (10.0%), and zingiberene (8.55%). However, further investigation could be carried out to examine the toxicity of the extract on animal models.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

All data are mentioned in the body of manuscript, tables, and figure.

References

  • Abdulhamid A, Awad TA, Ahmed AE, Koua FHM, Ismail AM (2021) Acetyleugenol from Acacia nilotica (L.) exhibits a strong antibacterial activity and its phenyl and indole analogues show a promising anti-TB potential targeting PknE/B protein kinases. Microbiology Research 12:1–15

    Article  Google Scholar 

  • AbuHammad S, Zihlif M (2013) Gene expression alterations in doxorubicin resistant MCF7 breast cancer cell line. Genomics 101:213–220

    Article  CAS  Google Scholar 

  • Abutaha NM, Farooq MF, Mohammed A-Z, Alotaibi A, Cordero MAW, Bepari A, Alarifi S (2021) Cytotoxic activity and toxicity study of HF8, a poly-herbal formulation. Journal of King Saud University-Science 33:101377

    Article  Google Scholar 

  • AlBasher G, Abdel-Daim MM, Almeer R, Ibrahim KA, Hamza RZ, Bungau S, Aleya L (2020) Synergistic antioxidant effects of resveratrol and curcumin against fipronil-triggered oxidative damage in male albino rats. Environ Sci Pollut Res 27:6505–6514

    Article  CAS  Google Scholar 

  • Barrios-González J (2018) Secondary metabolites production: physiological advantages in solid-state fermentation. Current Developments in Biotechnology and Bioengineering 257–283. https://doi.org/10.1016/B978-0-444-63990-5.00013-X

  • Blumen H, Fitch K, Polkus V (2016) Comparison of treatment costs for breast cancer, by tumor stage and type of service. American Health & Drug Benefits 9:23

    Google Scholar 

  • Buolamwini JK (1999) Novel anticancer drug discovery. Curr Opin Chem Biol 3:500–509

    Article  CAS  Google Scholar 

  • Çeli̇k K, Toğar B, Türkez H, TAŞPINAR N, (2014) In vitro cytotoxic, genotoxic, and oxidative effects of acyclic sesquiterpene farnesene. Turk J Biol 38:253–259

    Article  CAS  Google Scholar 

  • Chen H, Tang X, Liu T, Jing L, Wu J (2019a) Zingiberene inhibits in vitro and in vivo human colon cancer cell growth via autophagy induction, suppression of PI3K/AKT/mTOR pathway and caspase 2 deactivation. J BUON 24:1470–1475

    Google Scholar 

  • Chen H, Yuan J, Hao J, Wen Y, Lv Y, Chen L, Yang X (2019) α-Humulene inhibits hepatocellular carcinoma cell proliferation and induces apoptosis through the inhibition of Akt signaling. Food and Chemical Toxicology 134:110830

    Article  CAS  Google Scholar 

  • Chen L, Qu C, Chen H, Xu L, Qi Q, Luo J, Wang K, Meng Z, Chen Z, Wang P (2014) Chinese herbal medicine suppresses invasion-promoting capacity of cancer-associated fibroblasts in pancreatic cancer. PLoS One 9:e96177

    Article  CAS  Google Scholar 

  • El-Sayed A, Aleya L, Kamel M (2021) Microbiota and epigenetics: promising therapeutic approaches? Environ Sci Pollut Res 28:49343–49361

    Article  Google Scholar 

  • El Hadri A, del Rio MG, Sanz J, Coloma AG, Idaomar M, Ozonas BR, González JB, Reus MIS (2010) Cytotoxic activity of α-humulene and transcaryophyllene from Salvia officinalis in animal and human tumor cells. An R Acad Nac Farm 76:343–356

    Google Scholar 

  • Fidyt K, Fiedorowicz A, Strządała L, Szumny A (2016) β-caryophyllene and β-caryophyllene oxide—natural compounds of anticancer and analgesic properties. Cancer Med 5:3007–3017

    Article  CAS  Google Scholar 

  • Guarducci C, Bonechi M, Boccalini G, Benelli M, Risi E, Di Leo A, Malorni L, Migliaccio I (2017) Mechanisms of resistance to CDK4/6 inhibitors in breast cancer and potential biomarkers of response. Breast Care 12:304–308

    Article  Google Scholar 

  • He K, Zhang X, Ren S, Sun J (2016) Identity mappings in deep residual networks. In: Leibe B, Matas J, Sebe N, Welling M (eds) Computer Vision – ECCV 2016. ECCV 2016. Lecture Notes in Computer Science, vol 9908. Springer, Cham. https://doi.org/10.1007/978-3-319-46493-0_38

  • Hidayathulla S, Shahat A, Ahamad S, Al Moqbil A, Alsaid M, Divakar D (2018) GC/MS analysis and characterization of 2-hexadecen-1-ol and beta sitosterol from Schimpera arabica extract for its bioactive potential as antioxidant and antimicrobial. J Appl Microbiol 124:1082–1091

    Article  CAS  Google Scholar 

  • Hussain A, Yadav MK, Bose S, Wang J-H, Lim D, Song Y-K, Ko S-G, Kim H (2016) Daesiho-Tang is an effective herbal formulation in attenuation of obesity in mice through alteration of gene expression and modulation of intestinal microbiota. PLoS One 11:e0165483

    Article  CAS  Google Scholar 

  • Iqbal E, Salim KA, Lim LB (2015) Phytochemical screening, total phenolics and antioxidant activities of bark and leaf extracts of Goniothalamus velutinus (Airy Shaw) from Brunei Darussalam. Journal of King Saud University-Science 27:224–232

    Article  Google Scholar 

  • Itokawa H, Hirayama F, Funakoshi K, Takeya K (1985) Studies on the antitumor bisabolane sesquiterpenoids isolated from Curcuma xanthorrhiza. Chem Pharm Bull 33:3488–3492

    Article  CAS  Google Scholar 

  • Jacob JN, Toloue M (2013) Biological studies of turmeric oil, Part 1: Selective in vitro anticancer activity of turmeric oil (TO) and TO-paclitaxel combination. Natural Product Communications 8:1934578X1300800632

    Article  Google Scholar 

  • Jeba C, Vaidyanathan R, Rameshkumar G (2011) Immunomodulatory activity of aqueous extract of Ocimum sanctum in rat. Int J Pharm Biomed Res 2:33–38

    Google Scholar 

  • Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA (2002) Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci 99:11946–11950

    Article  CAS  Google Scholar 

  • Kandeil MA, Mohammed ET, Hashem KS, Aleya L, Abdel-Daim MM (2020) Moringa seed extract alleviates titanium oxide nanoparticles (TiO2-NPs)-induced cerebral oxidative damage, and increases cerebral mitochondrial viability. Environ Sci Pollut Res 27:19169–19184

    Article  CAS  Google Scholar 

  • Kumar PS, Febriyanti RM, Sofyan FF, Luftimas DE, Abdulah R (2014) Anticancer potential of Syzygium aromaticum L. in MCF-7 human breast cancer cell lines. Pharmacognosy research 6:350

    Article  CAS  Google Scholar 

  • Kummar S, Copur MS, Rose M, Wadler S, Stephenson J, O’Rourke M, Brenckman W, Tilton R, Liu S-H, Jiang Z (2011) A phase I study of the chinese herbal medicine PHY906 as a modulator of irinotecan-based chemotherapy in patients with advanced colorectal cancer. Clin Colorectal Cancer 10:85–96

    Article  CAS  Google Scholar 

  • Lichota A, Gwozdzinski K (2018) Anticancer activity of natural compounds from plant and marine environment. Int J Mol Sci 19:3533

    Article  CAS  Google Scholar 

  • Loizzo M, Tundis R, Menichini F, Saab A, Statti G, Menichini F (2008) Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells. Cell Prolif 41:1002–1012

    Article  CAS  Google Scholar 

  • Love RR, Leventhal H, Easterling DV, Nerenz DR (1989) Side effects and emotional distress during cancer chemotherapy. Cancer 63:604–612

    Article  CAS  Google Scholar 

  • Mhaidat NM, Bouklihacene M, Thorne RF (2014) 5-Fluorouracil-induced apoptosis in colorectal cancer cells is caspase-9-dependent and mediated by activation of protein kinase C-δ. Oncol Lett 8:699–704

    Article  CAS  Google Scholar 

  • Miron VV, Bottari NB, Assmann CE, Stefanello N, da Costa P, Pelinson LP, Reichert KP, da Silva AD, Lopes TF, da Cruz IBM (2019) Physical exercise prevents alterations in purinergic system and oxidative status in lipopolysaccharide-induced sepsis in rats. J Cell Biochem 120:3232–3242

    Article  CAS  Google Scholar 

  • Mohammed ET, Radi AM, Aleya L, Abdel-Daim MM (2020) Cynara scolymus leaves extract alleviates nandrolone decanoate-induced alterations in testicular function and sperm quality in albino rats. Environ Sci Pollut Res 27:5009–5017

    Article  CAS  Google Scholar 

  • Mohammed ET, Safwat GM (2020) Grape seed proanthocyanidin extract mitigates titanium dioxide nanoparticle (TiO2-NPs)-induced hepatotoxicity through TLR-4/NF-κB signaling pathway. Biol Trace Elem Res 196:579–589

    Article  CAS  Google Scholar 

  • Mooney L, Al-Sakkaf K, Brown B, Dobson P (2002) Apoptotic mechanisms in T47D and MCF-7 human breast cancer cells. Br J Cancer 87:909–917

    Article  CAS  Google Scholar 

  • Mukherjee AK, Saviola AJ, Burns PD, Mackessy SP (2015) Apoptosis induction in human breast cancer (MCF-7) cells by a novel venom L-amino acid oxidase (Rusvinoxidase) is independent of its enzymatic activity and is accompanied by caspase-7 activation and reactive oxygen species production. Apoptosis 20:1358–1372

    Article  CAS  Google Scholar 

  • Murunikkara V, Rasool M (2014) Trikatu, an herbal compound as immunomodulatory and anti-inflammatory agent in the treatment of rheumatoid arthritis—an experimental study. Cell Immunol 287:62–68

    Article  CAS  Google Scholar 

  • Nannizzi S, Veal GJ, Giovannetti E, Mey V, Ricciardi S, Ottley CJ, Del Tacca M, Danesi R (2010) Cellular and molecular mechanisms for the synergistic cytotoxicity elicited by oxaliplatin and pemetrexed in colon cancer cell lines. Cancer Chemother Pharmacol 66:547–558

    Article  CAS  Google Scholar 

  • Němcová-Fürstová V, Kopperová D, Balušíková K, Ehrlichová M, Brynychová V, Václavíková R, Daniel P, Souček P, Kovář J (2016) Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters. Toxicol Appl Pharmacol 310:215–228

    Article  CAS  Google Scholar 

  • NIST (2008): Chemistry Web Book, Mallard, W.G., Linstrom, P.J., Eds. NIST Standard Reference Database, National Institute of Standards and Technology. https://webbook.nist.gov. Accessed 15 Nov 2021

  • Nurgali K, Jagoe RT, Abalo R (2018) Adverse effects of cancer chemotherapy: anything new to improve tolerance and reduce sequelae? Front Pharmacol 9:245

    Article  CAS  Google Scholar 

  • Paula-Freire LIGd, Andersen M, Gama V, Molska G, Carlini E (2014) The oral administration of trans-caryophyllene attenuates acute and chronic pain in mice. Phytomedicine 21:356–362

    Article  CAS  Google Scholar 

  • Pirnia F, Schneider E, Betticher D, Borner M (2002) Mitomycin C induces apoptosis and caspase-8 and-9 processing through a caspase-3 and Fas-independent pathway. Cell Death Differ 9:905–914

    Article  CAS  Google Scholar 

  • Ramana KV, Singhal SS, Reddy AB (2014) Therapeutic potential of natural pharmacological agents in the treatment of human diseases. BioMed Research International 2014:4. https://doi.org/10.1155/2014/573452

  • Rosas-Ramírez DG, Fragoso-Serrano M, Escandón-Rivera S, Vargas-Ramírez AL, Reyes-Grajeda JP, Soriano-García M (2017) Resistance-modifying activity in vinblastine-resistant human breast cancer cells by oligosaccharides obtained from mucilage of chia seeds (Salvia hispanica). Phytother Res 31:906–914

    Article  CAS  Google Scholar 

  • Safwat GM, Hassanin K, Mohammed ET, Ahmed EK, Abdel Rheim MR, Ameen MA, Abdel-Aziz M, Gouda AM, Peluso I, Almeer R (2021) Synthesis, anticancer assessment, and molecular docking of novel chalcone-thienopyrimidine derivatives in HepG2 and MCF-7 cell lines. Oxidative Med Cell Longev 2021:27. https://doi.org/10.1155/2021/4759821

  • Seca AM, Pinto DC (2018) Plant secondary metabolites as anticancer agents: successes in clinical trials and therapeutic application. Int J Mol Sci 19:263

    Article  CAS  Google Scholar 

  • Shin S-A, Moon SY, Kim W-Y, Paek S-M, Park HH, Lee CS (2018) Structure-based classification and anti-cancer effects of plant metabolites. Int J Mol Sci 19:2651

    Article  CAS  Google Scholar 

  • Shin Y, Lee Y (2013) Cytotoxic activity from Curcuma zedoaria through mitochondrial activation on ovarian cancer cells. Toxicological Research 29:257–261

    Article  Google Scholar 

  • Silva FA, Borges F, Guimarães C, Lima JL, Matos C, Reis S (2000) Phenolic acids and derivatives: studies on the relationship among structure, radical scavenging activity, and physicochemical parameters. J Agric Food Chem 48:2122–2126

    Article  CAS  Google Scholar 

  • Singh S, Sharma B, Kanwar SS, Kumar A (2016) Lead phytochemicals for anticancer drug development. Front Plant Sci 7:1667

    Article  Google Scholar 

  • Singh V, Kumar K, Purohit D, Verma R, Pandey P, Bhatia S, Malik V, Mittal V, Rahman MH, Albadrani GM (2021) Exploration of therapeutic applicability and different signaling mechanism of various phytopharmacological agents for treatment of breast cancer. Biomedicine & Pharmacotherapy 139:111584

    Article  CAS  Google Scholar 

  • Sivakumaran N, Samarakoon SR, Adhikari A, Ediriweera MK, Tennekoon KH, Malavige N, Thabrew I, Shrestha RLS (2018) Cytotoxic and apoptotic effects of govaniadine isolated from Corydalis govaniana wall. roots on human breast cancer (MCF-7) Cells. BioMed Research International 2018. https://doi.org/10.1155/2018/3171348

  • Wong SP, Leong LP, Koh JHW (2006) Antioxidant activities of aqueous extracts of selected plants. Food Chem 99:775–783

    Article  CAS  Google Scholar 

  • Wu S, Zhu W, Thompson P, Hannun YA (2018) Evaluating intrinsic and non-intrinsic cancer risk factors. Nat Commun 9:1–12

    CAS  Google Scholar 

  • Yamasaki-Miyamoto Y, Yamasaki M, Tachibana H, Yamada K (2009) Fucoidan induces apoptosis through activation of caspase-8 on human breast cancer MCF-7 cells. J Agric Food Chem 57:8677–8682

    Article  CAS  Google Scholar 

  • Zarlaha A, Kourkoumelis N, Stanojkovic T, Kovala-Demertzi D (2014) Cytotoxic activity of essential oil and extracts of ocimum basilicum against human carcinoma cells. Molecular docking study of isoeugenol as a potent Cox and Lox inhibitor. Digest Journal of Nanomaterials & Biostructures (DJNB) 9:907–917

Download references

Funding

Funding was provided by King Saud University, Riyadh, Saudi Arabia, Researchers Supporting Project number (RSP-2021/112).

Author information

Authors and Affiliations

  1. Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Ahmed I. Alsayadi, Nael Abutaha, Bader O. Almutairi, Fahd A. Al-Mekhlafi & Mohamed A. Wadaan

Authors
  1. Ahmed I. Alsayadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nael Abutaha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bader O. Almutairi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fahd A. Al-Mekhlafi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohamed A. Wadaan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, N.A.; methodology, A.A., N.A., B.A., M.W., F.A.; software, N.A., B.A., A.A.; writing—original draft, preparation, N.A. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Nael Abutaha.

Ethics declarations

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Responsible Editor: Mohamed M. Abdel-Daim

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alsayadi, A.I., Abutaha, N., Almutairi, B.O. et al. Evaluating the efficacy of an innovative herbal formulation (HF6) on different human cancer cell lines. Environ Sci Pollut Res 29, 51768–51777 (2022). https://doi.org/10.1007/s11356-022-19529-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-022-19529-9

Keywords

Search

Navigation