Asparagus Racemosus Leaf Extract Inhibits Growth of UOK 146 Renal Cell Carcinoma Cell Line: Simultaneous Oncogenic PRCCTFE3 Fusion Transcript Inhibition and Apoptosis Independent Cell Death

  • Published : 2014.03.01


Aims: To evaluate anti-cancer activity of Asparagus racemosus (AR) leaf extract on UOK146, a renal cell carcinoma cell line, and explore its mechanism of action. Materials and Methods: Dried AR leaves were extracted with chloroform and dissolved in DMSO. This extract was applied to UOK146 and cell death was estimated by MTT assay. In addition PRCC-TFE3 fusion transcripts were detected by real time PCR. Results: Extract was found to be cytotoxic with an $IC_{50}$ of 0.9 mg/ml as estimated by dose response curve. Antitumor activity of the permissible doses of the extract was assessed by the down regulation of PRCC-TFE3 fusion transcript (38%) responsible for oncogenicity of the UOK146 cell line. No increment in the BAX, a proapoptotic marker level was observed. Conclusions: Evidence of antiproliferative effect, PRCC-TFE3 fusion transcript inhibition and static BAX level clearly indicate that AR extract provides or elicits an apoptosis independent anticancer effect on RCC cells by some specific mechanism of regulation.


  1. Agrawal A, Sharma M, Rai SK, et al (2008). The effect of the aqueous extract of the roots of Asparagus racemosus on hepatocarcinogenesis initiated by diethylnitrosamine. Phytother Res, 22, 1175-82.
  2. Battu GR, Kumar BM (2010). Anti-inflammatory activity of leaf extract of asparagus racemosus willd. Int J Chem Sci, 8, 1329-38.
  3. Bhatnagar M, Sisodia SS, Bhatnagar R (2005). Antiulcer and anti-oxidant activity of Asparagus racemosus Willd and Withania somnifera Dunal in rats. Ann NY Acad Sci, 1056, 261-78.
  4. Bhutani KK, Paul AT, Fayad W, Linder S (2010). Apoptosis inducing activity of steroidal constituents from Solanum xanthocarpum and Asparagus racemosus. Phytomedicine, 17, 789-93.
  5. Bousserouel S, Le Grandois J, Gosse F, et al (2013). Methanolic extract of white asparagus shoots activates TRAIL apoptotic death pathway in human cancer cells and inhibits colon carcinogenesis in a preclinical model. Int J Oncol, 43, 394-404.
  6. Cragg GM, Newman DJ (2005). Plants as a source of anti-cancer agents. J Ethnopharmacol, 100, 72-9.
  7. Diwanay S, Gautam M, Patwardhan B (2004). Cytoprotection and Immunomodulation in Cancer Therapy. Curr Med Chem Anticancer Agents, 4, 479-90.
  8. Gautam M, Diwanay S, Gairola S, et al (2004). Immunoadjuvant potential of Asparagus racemosus aqueous extract in experimental system. J Ethnopharmacol, 91, 251-5.
  9. Gautam M, Saha S, Bani S, et al (2009). Immunomodulatory activity of Asparagus racemosus on systemic Th1/Th2 immunity: Implications for immunoadjuvant potential. J Ethnopharmacol, 121, 241-7.
  10. Hannan JM, Marenah L, Ali L, et al (2007). Insulin secretory actions of extracts of Asparagus racemosus root in perfused pancreas, isolated islets and clonal pancreatic $\beta$-cells. J Endocrinol, 192, 59-168.
  11. Harborne JB (1973). Phytochemical Methods. Chapman and Hall Ltd., London, 49-188.
  12. Hayes PY, Jahidin AH, Lehmann R, et al (2006). Structural revision of shatavarins I and IV, the major components from the roots of Asparagus racemosus. Tetrahedron Lett, 47, 6965-9.
  13. Hayes PY, Jahidin AH, Lehmann R, et al (2008). Steroidal saponins from the roots of Asparagus racemosus. Phytochemistry, 69, 796-804.
  14. Ito TK, Ishii G, Chiba H, Ochiai A (2007). The VEGF angiogenic switch of fibroblasts is regulated by MMP-7 from cancer cells. Oncogene, 8, 7194-203.
  15. Kamat JP, Boloor KK, Devasagayam TPA, Venkatachalam SR (2000). Antioxidant properties of Asparagus racemosus against damage induced by $\gamma$-radiation in rat liver mitochondria. J Ethnopharmacol, 71, 425-35.
  16. Kongkaneramit L, Witoonsaridsilp W, Peungvicha P, et al (2011). Antioxidant activity and antiapoptotic effect of Asparagus racemosus root extracts in human lung epithelial H460 cells. Exp Ther Med, 2, 143-8.
  17. Liu FT, Agrawal SG, Gribben JG, et al (2008). Bortezomib blocks Bax degradation in malignant B cells during treatment with TRAIL. Blood, 111, 2797-805.
  18. Macher-Goeppinger S, Roth W, Wagener N, et al (2012). Molecular heterogeneity of TFE3 activation in renal cell carcinomas. Mod Pathol, 25, 308-15.
  19. Meena J, Ojha R, Muruganandam AV, Krishnamurthy S (2011). Asparagus racemosus competitively inhibits in vitro the acetylcholine and monoamine metabolizing enzymes. Neurosci Lett, 503, 6-9.
  20. Mohan S, Mohanasenthil, Paul S, Shroff S, Venkatesan V (2009). Interleukin-4-receptor alpha gene polymorphism and the risk of renal cell carcinoma in a South Indian population. Asian Pac J Cancer Prev, 10, 295-8.
  21. Parihar MS, Hemnani T (2004). Experimental excitotoxicity provokes oxidative damage in mice brain and attenuation by extract of Asparagus racemosus. J Neural Transm, 111, 1-12.
  22. Sekine T, Ikegami F, Fukasawa N (1995). Structure and relative stereochem- istry of a new polycyclic alkaloid, AsparagamineA, showing anti-oxytocin activity, isolated from Asparagus racemosus. J Chem Soc Perkin Trans, 4, 391-3.
  23. Sekine T, Fukasawa N, Murakoshi I, Ruangrungsi N (1997). A 9,10-dihydrophenanthrene from Asparagus racemosus. Phytochemistry, 44, 763-4.
  24. Shao Y, Chin CK, Ho CT, et al (1996). Anti-tumor activity of the crude saponins obtained from asparagus. Cancer Lett, 104, 31-6.
  25. Sidhar SK, Clark J, Gill S, et al (1996). The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene. Hum Mol Genet, 5, 1333-8.
  26. Sofowora A (1993). Medicinal Plants and Traditional Medicine in Africa. Spectrum Books Ltd., Ibadan, Nigeria, 191-289.
  27. Thakur M, Connellan P, Deseo MA, et al (2012). Characterization and in vitro immunomodulatory screening of fructooligosaccharides of Asparagus racemosus Willd. Int J Biol Macromol, 50, 77-81.
  28. Tanriverdi O (2013). Review on targeted treatment of patients with advanced-stage renal cell carcinoma: a medical oncologist's perspective. Asian Pac J Cancer Prev, 14, 609-17.
  29. Trease GE, Evans WC (1989). Pharmacognosy. 11th ed., Bailliere Tindall, London, 45-50.
  30. Weterman MA, van Groningen JJ, den Hartog A, Geurts van Kessel A (2001). Transformation capacities of the papillary renal cell carcinoma-associated PRCCTFE3 and TFE3PRCC fusion genes. Oncogene, 20, 1414-24.
  31. Wiboonpun N, Phuwapraisirisan P, Tip-pyang S (2004). Identification of antioxidant compound from Asparagus racemosus. Phytother Res, 18, 771-3.

Cited by

  1. Aqueous Extract of Anticancer Drug CRUEL Herbomineral Formulation Capsules Exerts Anti-proliferative Effects in Renal Cell Carcinoma Cell Lines vol.16, pp.18, 2016,
  2. vol.51, pp.11-12, 2017,
  3. Sodium butyrate induces cell death by autophagy and reactivates a tumor suppressor gene DIRAS1 in renal cell carcinoma cell line UOK146 vol.54, pp.4, 2018,
  4. Monensin induces cell death by autophagy and inhibits matrix metalloproteinase 7 (MMP7) in UOK146 renal cell carcinoma cell line pp.1543-706X, 2018,