(+)-Spectaline and Iso-6-Spectaline Induce a Possible Cross-Talk between Autophagy and Apoptosis in Trypanosoma brucei rhodesiense

• Main Authors: Ilham Adenan, Mohd (Author), Lim, K.T (Author), Yeoh, C.Y (Author), Zainuddin, Z. (Author)
• Format: Article
• Language: English
• Published: MDPI AG 2019
• Subjects: (+)-spectaline; African trypanosomiasis; antitrypanosomal activity; antitrypanosomal agent; apoptosis; Apoptosis; Article; Autophagy; autophagy (cellular); caspase; concentration response; controlled study; Cross-talk; DNA fragmentation; drug exposure; enzyme activation; IC50; iso 6 spectaline; Iso-6-spectaline; mitochondrial membrane potential; nonhuman; piperidine derivative; spectaline; Trypanosoma brucei rhodesiense; unclassified drug
• Online Access: View Fulltext in Publisher; View in Scopus

 In our previous study, two known piperidine alkaloids (+)-spectaline (1) and iso-6-spectaline (2) were isolated from the leaves of Senna spectabilis and showed no toxic effect on L6 cells. In view of the potential use of piperidine alkaloids in S. spectabilis for the treatment of sleeping sickness, further investigation on the cell death actions of the parasite after treatment with compound 1 and 2 suggested that the treated parasites died by a process of autophagy based on the characteristic morphological alterations observed in intracellular T. b. rhodesiense. In search for apoptosis, interestingly, trypanosomes treated with high concentration of compound 1 and 2 after 72 h significantly induced an early apoptosis-like programmed cell death (PCD) such as phosphatidylserine (PS) exposure, loss of mitochondrial membrane potential and caspases activation. No DNA laddering discriminated late apoptosis event. Taken together, these findings demonstrated the potential of compound 1 and 2 as a natural chemotherapeutic capable of inducing a possible cross-talk between autophagy and apoptosis in T. b. rhodesiense. © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).