Research Article Pfaffosidic Fraction from Hebanthe paniculata Induces Cell Cycle Arrest and Caspase-3-Induced Apoptosis in HepG2 Cells Tereza Cristina da Silva, 1 Bruno Cogliati, 1 Andréia Oliveira Latorre, 1 Gokithi Akisue, 2 Márcia Kazumi Nagamine, 1 Mitsue Haraguchi, 3 Daiane Hansen, 3 Daniel Soares Sanches, 1 and Maria Lúcia Zaidan Dagli 1 1 Department of Pathology, School of Veterinary Medicine and Animal Science, University of S˜ ao Paulo, Avenida Prof. Dr. Orlando Marques de Paiva 87, Cidade Universit´ aria, 05508-900 S˜ ao Paulo, SP, Brazil 2 School of Pindamonhangaba, Avenida Nossa Senhora do Bom Sucesso 3344, Campo Alegre, 12420-010 Pindamonhangaba, SP, Brazil 3 Section of Pharmacology, Division of Animal Biology, Biological Institute of S˜ ao Paulo, Avenida Conselheiro Rodrigues Alves 1.252, Vila Mariana, 04014-002 S˜ ao Paulo, SP, Brazil Correspondence should be addressed to Tereza Cristina da Silva; terezacs@usp.br Received 14 January 2015; Revised 26 March 2015; Accepted 17 April 2015 Academic Editor: Chong-Zhi Wang Copyright © 2015 Tereza Cristina da Silva et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hebanthe paniculata roots (formerly Pfaia paniculata and popularly known as Brazilian ginseng) show antineoplastic, chemopreventive, and antiproliferative properties. Functional properties of these roots and their extracts are usually attributed to the pfafosidic fraction, which is composed mainly by pfafosides A–F. However, the therapeutic potential of this fraction in cancer cells is not yet entirely understood. his study aimed to analyze the antitumoral efects of the puriied pfafosidic fraction or saponinic fraction on the human hepatocellular carcinoma HepG2 cell line. Cellular viability, proliferation, and apoptosis were evaluated, respectively, by MTT assay, BrdU incorporation, activated caspase-3 immunocytochemistry, and DNA fragmentation assay. Cell cycle was analyzed by low cytometry and the cell cycle-related proteins were analyzed by quantitative PCR and Western blot. he cells exposed to pfafosidic fraction had reduced viability and cellular growth, induced G2/M at 48 h or S at 72 h arrest, and increased sub-G1 cell population via cyclin E downregulation, p27 KIP1 overexpression, and caspase-3-induced apoptosis, without afecting the DNA integrity. Antitumoral efects of pfafosidic fraction from H. paniculata in HepG2 cells originated by multimechanisms of action might be associated with cell cycle arrest in the S phase, by CDK2 and cyclin E downregulation and p27 KIP1 overexpression, besides induction of apoptosis through caspase-3 activation. 1. Introduction Hepatocellular carcinoma (HCC) is known as the 5th most common human cancer in the world; and it has the third highest mortality rate among all cancers [1]. Despite major eforts to improve treatment of HCC, therapeutic options remain limited. herapies with pharmacological agents or alternative strategies fail to substantially improve the progno- sis of patients with unresectable HCC [2]. herefore, it is nec- essary to discover novel agents that can be used as adjuvant for HCC therapy [3]. In this manner, Hebanthe paniculata a plant traditionally used in Brazilian folk medicine has drawn attention to its antineoplastic efects on several animal and cell models [4–8]. Hebanthe paniculata (formerly known as Pfaia panic- ulata) belongs to the Amaranthaceae family and is popu- larlyknown as Brazilian ginseng. Its main components are stigmasterol, sitosterol, allantoin, pfaic acid, and glycosides, which are triterpenoid saponins, denominated pfafosides A, B, C, D, E, and F [9]. hese saponins are considered the main active components of H. paniculata roots and have several biological properties described [10]. Previous studies from our group showed antineoplastic efects of H. paniculata roots and its extracts on several Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2015, Article ID 835796, 9 pages http://dx.doi.org/10.1155/2015/835796