title: Assessment of the in vitro cytotoxicity and in vivo anti-tumor activity of the alcoholic stem bark extract/fractions of Mimusops elengi Linn.
abstract: Various parts of Mimusops elengi Linn. (Sapotaceae) have been used widely in traditional Indian medicine for the treatment of pain, inflammation and wounds. The study was conducted to explore the use of stem bark of M. elengi on pharmacological grounds and to evaluate the scientific basis of cytotoxic and anti-tumor activity. Extract/fractions were prepared and in vitro cytotoxicity was assessed using SRB assay. Most effective fractions were subjected to fluorescence microscopy based acridine orange/ethidium bromide (AO/EB) and Hoechst 33342 staining to determine apoptosis induction and DNA fragmentation assay. Comet and micronuclei assay were performed to assess genotoxicity. Cell cycle analysis was also performed. In vivo anti-tumor potential was evaluated by Ehrlich ascites carcinoma (EAC) model in mice. The alcoholic stem bark extract of M. elengi along with four fractions showed potential in vitro cytotoxicity in SRB assay. Of these, dichloromethane and ethyl acetate fractions were selected for further studies. The fractions revealed apoptosis inducing potential in AO/EB and Hoechst 33342 staining, which was further confirmed by DNA fragmentation assay. Genotoxic potential was revealed by comet and micronuclei assay. Fractions also exhibited specific cell cycle inhibition in G0/G1 phase. In EAC model, ethyl acetate fraction along with the standard (cisplatin) effectively reduced the increase in body weight compared to control and improved mean survival time. Both fractions were able to restore the altered hematological and biochemical parameters. Hence, M. elengi stem bark may be a possible therapeutic candidate having cytotoxic and anti-tumor potential.
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India.
authors.forename: Harish
authors.initials: H
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India.
authors.forename: Mihir
authors.initials: M
authors.lastname: Savaliya
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India.
authors.forename: Subhankar
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India.
authors.forename: Pawan G
authors.initials: PG
authors.lastname: Nayak
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India.
authors.forename: Naseer
authors.initials: N
authors.lastname: Maliyakkal
authors.affiliation: Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India.
authors.forename: M
authors.initials: M
authors.lastname: Manjunath Setty
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India.
authors.forename: Karthik
authors.initials: K
authors.lastname: Gourishetti
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India. ksr.pai@manipal.edu.
authors.forename: K Sreedhara Ranganath
authors.initials: KS
authors.lastname: Pai
keywords: Acridine orange/ethidium bromide (AO/EB) staining; Antioxidants; Comet assay; Flow cytometry; Sulforhodamine B (SRB) assay