Anticancer Effect of Marine Sponge-Associated Bacillus pumilus AMK1 Derived Dipeptide Cyclo (-Pro-Tyr) in Human Liver Cancer Cell Line Through Apoptosis and G2/M Phase Arrest
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The present study was initiated to identify a novel cytotoxic bioactive molecule from marine sponge Callyspongia fistularis symbionts and to investigate its apoptotic role on human liver cancer cell line (HepG2). The extracts of all the isolated strains (AMK1–AMK12) from sponge Callyspongia fistularis were screened based on cytotoxicity on HepG2 cell line, among them AMK1 showed the significant cytotoxic activity. The strain AMK1 was identified as Bacillus pumilus based on 16S rRNA sequencing and biochemical tests. Further purifying the bio-molecules responsible for the cytotoxic activity by different spectral analysis led to the identification of dipeptide Cyclo(-Pro-Tyr), that showed promising cytotoxic activity and apoptotic inducing activity on HepG2 liver cancer cell line with an IC50 value of 42.98 µg/mL. The effect of Cyclo(-Pro-Tyr) induced apoptosis of HepG2 cells was indicated by nuclear morphology, PI staining, AO/EB staining and cell cycle arrest by flow cytometry analysis. These findings suggest that Cyclo(-Pro-Tyr) isolated from B.pumilusAMK1 may contribute as a novel anticancer molecule, forming an important strategy for developing alternative therapies to treat liver cancer with natural molecule without affecting the normal cells.
KeywordsMarine sponges Symbiont Apoptosis Cell cycle arrest Cyclo(-Pro-Tyr)
The authors wish to thank Dr. G. Sivaleela, Scientist C, Zoological survey of India for her support in the identification of marine sponge species. Also, the authors wish to thank Dr.Malini, Sri Ramachandra Medical College and Research Institute for her help to carryout flow cytometry studies. The structural characterization was done with the help of scientist Dr. M. Rajasekhar, chemist, Sathyabama Institute of Science and Technology, Chennai.
The corresponding author is also grateful for the grant sanctioned by Department of Biotechnology, Aquaculture and Marine Biotechnology, Govt of India under the taskforce (BT/PR11664/AAQ/3/682/2014) research grant.
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Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
In this type of study, formal consent is not required.
- Arbsuwan N, Payoungkiattikun W, Sirithorn P, Daduang S, Jangpromma N, Dhiravisit A, Hahm YT, Neubert LK, Klaynongsruang S (2018) Purification and characterization of macrolactins and amicoumacins from Bacillus licheniformis BFP011: a new source of food antimicrobial substances. CyTA-J Food 16:50–60. https://doi.org/10.1080/19476337.2017.1337047 CrossRefGoogle Scholar
- Baskar R, Rajeswari V, Kumar TS (2007) In vitro antioxidant studies in leaves of Annona species. Indian J Exp Biol 45(5):480–485Google Scholar
- Esmaeili MA, Farimani MM, Kiaei M (2014) Anticancer effect of calycopterin via PI3K/Akt and MAPK signaling pathways, ROS-mediated pathway and mitochondrial dysfunction in hepatoblastoma cancer (HepG2) cells. Mol Cell Biochem 397:17–31. https://doi.org/10.1007/s11010-014-2166-4 CrossRefPubMedCentralGoogle Scholar
- Hong S, Moon BH, Yong Y, Shin SY, Lee YH, Lim Y (2008) Inhibitory effect against Akt of cyclic dipeptides isolated from Bacillus sp. J Microbiol Biotechnol 18(4):682–685Google Scholar
- Madankumar A, Jayakumar S, Gokuladhas K, Rajan B (2013) Geraniol modulates tongue and hepatic phase I and phase II conjugation activities and may contribute directly to the chemopreventive activity against experimental oral carcinogenesis. Eur J Pharmacol 705:148–155. https://doi.org/10.1016/j.ejphar.2013.02.048 CrossRefGoogle Scholar
- Prakash S, Sasikala SL, Huxley Aldous VJ (2010) Isolation and identification of MDR-Mycobacterium tuberculosis and screening of partially characterized antimycobacterial compounds from chosen marine micro algae. Asian Pac J Trop Med 3:655–661. https://doi.org/10.1016/S1995-7645(10)60158-7 CrossRefGoogle Scholar
- Thomadaki H, Tsiapalis CM, Scorilas A (2005) Polyadenylate polymerase modulations in human epithelioid cervix and breast cancer cell lines, treated with etoposide or cordycepin, follow cell cycle rather than apoptosis induction. Biol Chem 386:471–480. https://doi.org/10.1515/bc.2005.056 CrossRefGoogle Scholar