Evaluation of Standardized Extract of Centella Asiatica on Cell Viability and Repressive Cancer Migration in Metastatic Colorectal Cancer Cells in Vitro


  • Suwisit MANMUAN Division of Pharmacology, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand
  • Ponwit MANMUAN Department of Intellectual Property, Ministry of Commerce, Nonthaburi 11000, Thailand
  • Punyo YOYKAEW Division of Pharmacy, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand
  • Piyachat THUETONG Division of Pharmacy, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand
  • Patchraporn ASIPONG Division of Pharmacy, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand
  • Nattanicha RIANTONG Division of Pharmacy, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand
  • Mayuree H. TANTISIRA Division of Pharmacology, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand




Cell survival, Colorectal cancer, ECa233, 5-Fluorouracil, Synergism


Centella Asiatica has been traditionally used as herbal medicine to treat various disorders, such as ulcers and psoriatic disease. ECa233 is an herbal extract of Centella Asiatica containing madecassoside (46.3 %) and asiaticoside (41.6 %) that shows a highly acceptable safety profile appropriate for drug development and use as an herbal drug for humans. 5-fluorouracil (5-FU) is a chemotherapeutic agent generally known as the first-line chemotherapy for colorectal cancer. Representative combined chemotherapy with 5-FU, namely the FOLFOX regimen (5-FU, leucovorin, oxaliplatin), has been widely used in hospitals and is typically selected as a chemotherapeutic regimen in prescriptions. However, the unresolved problems appearing in clinical situations are the refusal to accept the chemotherapy leading to drug resistance and the severe side effects after being administered intravenously to the entire body. Therefore, the discovery of a novel pure standard agent to enhance the efficacy of 5-FU and overcome this drug resistance still needs to be explored. To assess the pharmacological activity and safety profile of ECa233 is a major goal in cancer drug discovery. ECa233 was evaluated for its anti-cancer, anti-migration, anti-invasive activities and was explored regarding the safety data on normal cells. The results demonstrated that ECa233 effectively inhibited the cell viability, colony forming, and truly inactivated cell migration/invasion through repressive the MMP-9 invasive factor. Pharmacological interaction with 5-FU was synergism in cancer cells and highly safe to normal cell growth. The results suggest that ECa233 could be used as a combinative drug therapy with standard chemotherapy treatment and other medicinal drugs such as a targeted therapy to treat colorectal cancer patients.


Download data is not yet available.


Metrics Loading ...


B Siripongpreeda, C Mahidol, N Dusitanond, T Sriprayoon, B Muyphuag, T Sricharunrat, N Teerayatanakul, W Chaiwong, W Worasawate, P Sattayarungsee, J Sangthongdee, J Prarom, G Sornsamdang, K Soonklang, K Wittayasak and CU Auewarakul. High prevalence of advanced colorectal neoplasia in the Thai population: a prospective screening colonoscopy of 1,404 cases. BMC Gastroenterol. 2016; 16,101.

Y Zhang, Z Chen and J Li. The current status of treatment for colorectal cancer in China: A systematic review. Medicine (Baltimore) 2017; 96, e8242.

CM Lund, D Nielsen, C Dehlendorff, AB Christiansen, F Rønholt, JS Johansen and KK Vistisen. Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer: The ACCORE study. ESMO Open 2016; 1, e000087.

G Masi, L Marcucci, F Loupakis, E Cerri, C Barbara, S Bursi, G Allegrini, IM Brunetti, R Murr, S Ricci, S Cupini, M Andreuccetti and A Falcone. First-line 5-fluorouracil/folinic acid, oxaliplatin and irinotecan (FOLFOXIRI) does not impair the feasibility and the activity of second line treatments in metastatic colorectal cancer. Ann Oncol. 2006; 17, 1249-54.

M Kotake, T Aoyama, Y Munemoto, K Doden, M Kataoka, K Kobayashi, G Nishimura, H Fujita, K Nakamura, A Takehara, C Tanaka, J Sakamoto, N Nagata, K Oba and K Kondo. Multicenter phase II study of infusional 5-fluorouracil (5-FU), leucovorin, and oxaliplatin, plus biweekly cetuximab as first-line treatment in patients with metastatic colorectal cancer (CELINE trial). Oncol. Lett. 2017; 13, 747-53.

S Giacchetti, B Perpoint, R Zidani, N Le Bail, R Faggiuolo, C Focan, P Chollet, JF Llory, Y Letourneau, B Coudert, F Bertheaut-Cvitkovic, D Larregain-Fournier, AL Rol, S Walter, R Adam, JL Misset and F Lévi. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin. Oncol. 2000; 18, 136-47.

XB Liang, SH Hou, YP Li, LC Wang, X Zhang and J Yang. Irinotecan or oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer: A meta-analysis. Chin. Med. J. (Engl). 2010; 123, 3314-8.

N Saijo. Present status and problems on molecular targeted therapy of cancer. Cancer Res. Treat. 2012; 44, 1-10.

JB Fitzgerald, B Schoeberl, UB Nielsen and PK Sorger. Systems biology and combination therapy in the quest for clinical efficacy. Nat. Chem. Biol. 2006; 2, 458-66.

R Bayat Mokhtari, TS Homayouni, N Baluch, E Morgatskaya, S Kumar, B Das and H Yeger. Combination therapy in combating cancer. Oncotarget 2017; 8, 38022-43.

MV Blagosklonny. Overcoming limitations of natural anticancer drugs by combining with artificial agents. Trends. Pharmacol. Sci. 2005; 26, 77-81.

EC Saputra, L Huang, Y Chen and L Tucker-Kellogg. Combination therapy and the evolution of resistance: The theoretical merits of synergism and antagonism in cancer. Cancer Res. 2018; 78, 2419-31.

VK Ngan, K Bellman, BT Hill, L Wilson and MA Jordan. Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine. Mol. Pharmacol. 2001; 60, 225-32.

H Ishikawa, DA Colby, S Seto, P Va, A Tam, H Kakei, TJ Rayl, I Hwang and DL Boger. Total synthesis of vinblastine, vincristine, related natural products, and key structural analogues. J. Am. Chem. Soc. 2009; 131, 4904-16.

O Wanakhachornkrai, V Pongrakhananon, P Chunhacha, A Wanasuntronwong, A Vattanajun, B Tantisira, P Chanvorachote and MH Tantisira. Neuritogenic effect of standardized extract of Centella asiatica ECa233 on human neuroblastoma cells. BMC Complement Altern. Med. 2013; 13, 204.

J Somboonwong, M Kankaisre, B Tantisira and MH Tantisira. Wound healing activities of different extracts of Centella asiatica in incision and burn wound models: an experimental animal study. BMC Complement Altern. Med. 2012; 12, 103.

A Wanasuntronwong, MH Tantisira, B Tantisira and H Watanabe. Anxiolytic effects of standardized extract of Centella asiatica (ECa 233) after chronic immobilization stress in mice. J. Ethnopharmacol. 2012; 143, 579-85.

S Doknark, S Mingmalairak, A Vattanajun, B Tantisira and MH Tantisira. Study of ameliorating effects of ethanolic extract of Centella asiatica on learning and memory deficit in animal models. J. Med. Assoc. Thai. 2014; 97, S68-76.

A Wanasuntronwong, O Wanakhachornkrai, P Phongphanphanee, T Isa, B Tantisira and MH Tantisira. Modulation of neuronal activity on intercalated neurons of amygdala might underlie anxiolytic activity of a standardized extract of centella asiatica ECa233. Evid. Based Complement Alternat. Med. 2018; 2018, 3853147.

N Teerapattarakan, H Benya-Aphikul, R Tansawat, O Wanakhachornkrai, MH Tantisira and R Rodsiri. Neuroprotective effect of a standardized extract of Centella asiatica ECa233 in rotenone-induced parkinsonism rats. Phytomedicine 2018; 44, 65-73.

S Chivapat, P Chavalittumrong and MH Tantisira. Acute and sub-chronic toxicity studies of a standardized extract of Centella asiatica ECa233. Thai. J. Pharm. Sci. 2011; 35, 55-64.

P Hengjumrut, T Anukunwithaya, MH Tantisira, B Tantisira and P Khemawoot. Comparative pharmacokinetics between madecassoside and asiaticoside presented in a standardised extract of Centella asiatica, ECa 233 and their respective pure compound given separately in rats. Xenobiotica 2018; 48, 18-27.

T Anukunwithaya, MH Tantisira, B Tantisira, P Khemawoot. Pharmacokinetics of a standardized extract of centella asiatica ECa 233 in rats. Planta Med. 2017; 83, 710-7.

P Songvut, P Chariyavilaskul, MH Tantisira and P Khemawoot. Safety and pharmacokinetics of standardized extract of centella asiatica (ECa 233) capsules in healthy Thai volunteers: A phase 1 clinical study. Planta Med. 2019; 85, 483-90.

TL Riss, RA Moravec, AL Niles, S Duellman, HA Benink, TJ Worzella, L Minor, S Markossian, GS Sittampalam, A Grossman, K Brimacombe, M Arkin, D Auld, CP Austin, J Baell, JMM Caaveiro, TDY Chung , NP Coussens, JL Dahlin, V Devanaryan, TL Foley, M Glicksman, MD Hall, JV Haas, SRJ Hoare, J Inglese, PW Iversen, SD Kahl, SC Kales, S Kirshner, M Lal-Nag, Z Li, J McGee, O McManus, T Riss, P Saradjian, OJ Trask, JR Weidner, MJ Wildey, M Xia and X Xu. Cell viability assays. In: Assay Guidance Manual. Bethesda (MD), 2004.

TC Chou. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010; 70, 440-6.

C Filgueiras Mde, A Morrot, PM Soares, ML Costa and C Mermelstein. Effects of 5-fluorouracil in nuclear and cellular morphology, proliferation, cell cycle, apoptosis, cytoskeletal and caveolar distribution in primary cultures of smooth muscle cells. PLoS One 2013; 8, e63177.

YS Jung, Y Qian and X Chen. Examination of the expanding pathways for the regulation of p21 expression and activity. Cell Signal 2010; 22, 1003-12.

P Bunpo, K Kataoka, H Arimochi, H Nakayama, T Kuwahara, Y Ohnishi and U Vinitketkumnuen. Centella asiatica extract induces cell cycle arrest in Caco-2 human colon cancer cells. Chiang Mai Med. Bull. 2005; 44, 21-28.

Y Hao, J Huang, Y Ma, W Chen, Q Fan, X Sun, M Shao and H Cai. Asiatic acid inhibits proliferation, migration and induces apoptosis by regulating Pdcd4 via the PI3K/ Akt/ mTOR/ p70S6K signaling pathway in human colon carcinoma cells. Oncol. Lett. 2018; 15, 8223-30.

J He, L Pei, H Jiang, W Yang, J Chen and H Liang. Chemoresistance of colorectal cancer to 5-fluorouracil is associated with silencing of the BNIP3 gene through aberrant methylation. J. Cancer 2017; 8, 1187-96.

M Shakibaei, P Kraehe, B Popper, P Shayan, A Goel and C Buhrmann. Curcumin potentiates antitumor activity of 5-fluorouracil in a 3D alginate tumor microenvironment of colorectal cancer. BMC Cancer 2015; 15, 250.

S Singkhorn, MH Tantisira, S Tanasawet, P Hutamekalin, T Wongtawatchai and W Sukketsiri. Induction of keratinocyte migration by ECa 233 is mediated through FAK/Akt, ERK, and p38 MAPK signaling. Phytother. Res. 2018; 32, 1397-403.

P Friedl and S Alexander. Cancer invasion and the microenvironment: Plasticity and reciprocity. Cell 2011; 147, 992-1009.

C Gialeli, AD Theocharis and NK Karamanos. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J. 2011; 278, 16-27.

SO Yoon, SJ Park, CH Yun and AS Chung. Roles of matrix metalloproteinases in tumor metastasis and angiogenesis. J. Biochem. Mol. Biol. 2003; 36, 128-37.

S Damery, L Nichols, R Holder, ST Ward, S Warmington, S Wilson, MJ Wakelam, J James and T Ismail. Assessing the value of matrix metalloproteinase 9 (MMP9) in improving the appropriateness of referrals for colorectal cancer. Br. J. Cancer 2013; 108, 1149-56.




How to Cite

MANMUAN, S. ., MANMUAN, P. ., YOYKAEW, P. ., THUETONG, P. ., ASIPONG, P. ., RIANTONG, N. ., & TANTISIRA, M. H. . (2021). Evaluation of Standardized Extract of Centella Asiatica on Cell Viability and Repressive Cancer Migration in Metastatic Colorectal Cancer Cells in Vitro. Walailak Journal of Science and Technology (WJST), 18(5), Article 9016 (18 pages). https://doi.org/10.48048/wjst.2021.9016