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

1
Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), National Institutes of Biotechnology Malaysia, Ministry of Science, Technology and Innovation, Blok 5-A, Halaman Bukit Gambir, Penang 11700, Malaysia
2
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia
3
Analytical Biochemistry Research Centre (ABrC), Universiti Sains Malaysia, Penang 11800, Malaysia
4
Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam 40450, Selangor, Malaysia
5
Universiti Teknologi MARA Pahang Campus, 26400 Bandar Tun Abdul Razak Jengka, Pahang, Malaysia
*
Author to whom correspondence should be addressed.
Trop. Med. Infect. Dis. 2019, 4(3), 98; https://doi.org/10.3390/tropicalmed4030098
Received: 17 May 2019 / Revised: 23 June 2019 / Accepted: 27 June 2019 / Published: 1 July 2019
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Abstract

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. View Full-Text
Keywords: (+)-spectaline; iso-6-spectaline; Trypanosoma brucei rhodesiense; autophagy; apoptosis; cross-talk (+)-spectaline; iso-6-spectaline; Trypanosoma brucei rhodesiense; autophagy; apoptosis; cross-talk
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This 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 (CC BY 4.0).
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MDPI and ACS Style

Lim, K.T.; Yeoh, C.Y.; Zainuddin, Z.; Ilham Adenan, M. (+)-Spectaline and Iso-6-Spectaline Induce a Possible Cross-Talk between Autophagy and Apoptosis in Trypanosoma brucei rhodesiense. Trop. Med. Infect. Dis. 2019, 4, 98.

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