<em>Dioscorea dumetorum</em> (bitter yam) tuber induces the apoptosis of liver cancer cells

Promise,Chinecherem Victory; Waziri,Peter Maitalata; Auta,Richard; Tyoapine,Daniel; Tahir,Mohammed I.; Ahmad,Abdurrahman E.

doi:10.3892/wasj.2025.325

Dioscorea dumetorum (bitter yam) tuber induces the apoptosis of liver cancer cells

Authors:
- Chinecherem Victory Promise
- Peter Maitalata Waziri
- Richard Auta
- Daniel Tyoapine
- Mohammed I. Tahir
- Abdurrahman E. Ahmad
View Affiliations

Affiliations: Department of Biochemistry, Kaduna State University, Kaduna 800283, Kaduna, Nigeria, Department of Medical Laboratory Science, Ahmadu Bello University, Zaria 810211, Kaduna, Nigeria
Published online on: February 14, 2025 https://doi.org/10.3892/wasj.2025.325
Article Number: 37
Copyright : © Promise et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Liver cancer is the sixth most prevalent type of cancer and the third most common cause of cancer‑related mortality worldwide. The treatment methods for liver cancer are very limited and no cure has yet been found for this disease. This situation has intensified the search for alternative treatment options in numerous developing countries. For example, the extract of Dioscorea dumetorum (D. dumetorum) tuber is used locally for the treatment of cancers. However, there is limited scientific evidence available to support the acclaimed therapeutic properties of D. dumetorum. Therefore, the present study aimed to investigate the in vitro anticancer effects of D. dumetorum on liver cancer (HepG2) cells. The cytotoxic effects of the chloroform fraction of D. dumetorum were examined using MTT assay and phase contrast microscopy. The effects of treatment with the chloroform fraction on the apoptosis of HepG2 cells were investigated using caspase assay and reverse transcription‑quantitative PCR. The chloroform fraction was cytotoxic to the cancer cell lines (IC50 28.5±0.01 µg/ml). The phase contrast microscopy of the HepG2 cells revealed morphological aberrations that suggested apoptosis. In addition, treatment with the chloroform fraction increased the expression levels of caspase‑3, ‑8 and ‑9 proteins, suggesting that HepG2 cell death may have occurred through apoptosis. Gene expression analysis revealed that treatment with the chloroform fraction increased the mRNA expression levels of p53 and Bax, whereas it decreased the mRNA expression levels of Bcl‑2 and MDM2. The findings of the present study corroborate the occurrence of apoptosis in the chloroform fraction‑treated HepG2 cancer cells. Therefore, D. dumetorum tuber extract may be potentially used for the induction of the apoptosis of liver cancer cells.

View Figures

View References

1	World Health Organization: Cancer: Key facts. WHO, Geneva, 2018. https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed February 7, 2019.
2	Tariq A, Sadia S, Pan K, Ullah I, Mussarat S, Sun F, Abiodun OO, Batbaatar A, Li Z, Song D, et al: A systematic review on ethnomedicines of anti-cancer plants. Phytother Res. 31:202–264. 2017.PubMed/NCBI View Article : Google Scholar
3	Aliyu-Amoo H, Isa HI, Njoya EM and McGaw LJ: Antiproliferative effect of extracts and fractions of the root of Terminalia avicennioides (Combretaceae) Guill and Perr. On HepG2 and Vero Cell Lines. Int J Phytomed Phytother. 7(71)2021.
4	Kadan S, Rayan M and Rayan A: Anticancer activity of anise (Pimpinella anisum L.) seed extract. Open Nutraceuticals J. 6:1–5. 2013.
5	Wang Z, Li Z, Ye Y, Xie L and Li W: Oxidative stress and liver cancer: Etiology and therapeutic targets. Oxid Med Cell Longev. 2016(7891574)2016.PubMed/NCBI View Article : Google Scholar
6	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021.PubMed/NCBI View Article : Google Scholar
7	Maluccio M and Covey A: Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J Clin. 62:394–399. 2012.PubMed/NCBI View Article : Google Scholar
8	Sun Y, Ma W, Yang Y, He M, Li A, Bai L, Yu B and Yu Z: Cancer nanotechnology: Enhancing tumor cell response to chemotherapy for hepatocellular carcinoma therapy. Asian J Pharm Sci. 14:581–594. 2019.PubMed/NCBI View Article : Google Scholar
9	Nekvindova J, Mrkvicova A, Zubanova V, Hyrslova Vaculova A, Anzenbacher P, Soucek P, Radova L, Slaby O, Kiss I, Vondracek J, et al: Hepatocellular carcinoma: Gene expression profiling and regulation of xenobiotic-metabolizing cytochromes P450. Biochem Pharmacol. 177(113912)2020.PubMed/NCBI View Article : Google Scholar
10	Florio AA, Campbell PT, Zhang X, Zeleniuch-Jacquotte A, Wactawski-Wende J, Smith-Warner SA, Sinha R, Simon TG, Sesso HD, Schairer C, et al: Abdominal and gluteofemoral size and risk of liver cancer: The liver cancer pooling project. Int J Cancer. 147:675–685. 2020.PubMed/NCBI View Article : Google Scholar
11	Manosroi A, Akazawa H, Kitdamrongtham W, Akihisa T, Manosroi W and Manosroi J: Potent antiproliferative effect on liver cancer of medicinal plants selected from the Thai/Lanna medicinal plant recipe database ‘MANOSROI III’. Evid Based Complement Alternat Med. 2015(397181)2015.PubMed/NCBI View Article : Google Scholar
12	Khalil R, Ali Q, Hafeez M and Malik A: Phytochemical activities of Conocarpus erectus: An overview. Biol Clin Sci Res J. 2020:1–6. 2020.
13	Kaur R, Kapoor K and Kaur H: Plants as a source of anticancer agents. J Nat Prod Plant Resour. 1:19–124. 2011.
14	Jesus M, Martins AP, Gallardo E and Silvestre S: Diosgenin: Recent highlights on pharmacology and analytical methodology. J Anal Methods Chem. 2016(4156293)2016.PubMed/NCBI View Article : Google Scholar
15	Salehi B, Sener B, Kilic M, Sharifi-Rad J, Naz R, Yousaf Z, Mudau FN, Fokou PVT, Ezzat SM, El Bishbishy MH, et al: Dioscorea plants: A genus rich in vital nutra-pharmaceuticals-A review. Iran J Pharm Res. 18(Suppl):68–89. 2019.PubMed/NCBI View Article : Google Scholar
16	Keshava R, Muniyappa N and Gope R: Bioactivity guided fractionation and elucidation of anti-cancer properties of Imperata cylindrica leaf extracts. Asian Pac J Cancer Prev. 21:707–714. 2020.PubMed/NCBI View Article : Google Scholar
17	Waziri PM, Abdullah R, Yeap SK, Omar AR, Kassim NK, Malami I, How CW, Etti IC and Abu ML: Clausenidin induces caspase-dependent apoptosis in colon cancer. BMC Complement Altern Med. 16(256)2016.PubMed/NCBI View Article : Google Scholar
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
19	Win DT: Oleic acid-The anti-breast cancer component in olive oil. AU J.T. 9:75–78. 2005.
20	Yu F, Lu S, Yu F, Shi J, McGuire PM and Wang R: Cytotoxic activity of an octadecenoic acid extract from Euphorbia kansui (Euphorbiaceae) on human tumour cell strains. J Pharm Pharmacol. 60:253–259. 2008.PubMed/NCBI View Article : Google Scholar
21	Sangpairoj K, Settacomkul R, Siangcham T, Meemon K, Niamnont N, Sornkaew N, Tamtin M, Sobhon P and Vivithanaporn P: Hexadecanoic acid-enriched extract of Halymenia durvillei induces apoptotic and autophagic death of human triple-negative breast cancer cells by upregulating ER stress. Asian Pac J Trop Biomed. 12:132–140. 2022.
22	Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007.PubMed/NCBI View Article : Google Scholar
23	Häcker G: The morphology of apoptosis. Cell Tissue Res. 301:5–17. 2000.PubMed/NCBI View Article : Google Scholar
24	Pfeffer CM and Singh ATK: Apoptosis: A target for anticancer therapy. Int J Mol Sci. 19(448)2018.PubMed/NCBI View Article : Google Scholar
25	Obeng E: Apoptosis (programmed cell death) and its signals-A review. Braz J Biol. 81:1133–1143. 2021.PubMed/NCBI View Article : Google Scholar
26	Lossi L: The concept of intrinsic versus extrinsic apoptosis. Biochem J. 479:357–384. 2022.PubMed/NCBI View Article : Google Scholar
27	Olsson M and Zhivotovsky B: Caspases and cancer. Cell Death Differ. 18:1441–1449. 2011.PubMed/NCBI View Article : Google Scholar
28	Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000.PubMed/NCBI View Article : Google Scholar
29	Nagata S: Apoptotic DNA fragmentation. Exp Cell Res. 256:12–18. 2000.PubMed/NCBI View Article : Google Scholar
30	Gross A, McDonnell JM and Korsmeyer SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13:1899–1911. 1999.PubMed/NCBI View Article : Google Scholar
31	Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T and Korsmeyer SJ: BCL-2, BCL-XL sequester BH3 domain-only molecules preventing BAX-and BAK-mediated mitochondrial apoptosis. Mol Cell. 8:705–711. 2001.PubMed/NCBI View Article : Google Scholar
32	Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB and Korsmeyer SJ: Proapoptotic BAX and BAK: A requisite gateway to mitochondrial dysfunction and death. Science. 292:727–730. 2001.PubMed/NCBI View Article : Google Scholar
33	Weinberg RA: How cancer arises. Sci Am. 275:62–70. 1996.PubMed/NCBI View Article : Google Scholar
34	Eischen CM: Role of Mdm2 and Mdmx in DNA repair. J Mol Cell Biol. 9:69–73. 2017.PubMed/NCBI View Article : Google Scholar
35	Chène P: Inhibiting the p53-MDM2 interaction: An important target for cancer therapy. Nat Rev Cancer. 3:102–109. 2003.PubMed/NCBI View Article : Google Scholar
36	Campbell KJ and Tait SWG: Targeting BCL-2 regulated apoptosis in cancer. Open Biol. 8(180002)2018.PubMed/NCBI View Article : Google Scholar
37	Jain AK and Barton MC: p53: Emerging roles in stem cells, development and beyond. Development. 145(dev158360)2018.PubMed/NCBI View Article : Google Scholar