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Toxins (Basel). 2016 Feb 5;8(2):38. doi: 10.3390/toxins8020038.

Apoptosis Activation in Human Lung Cancer Cell Lines by a Novel Synthetic Peptide Derived from Conus californicus Venom.

Author information

1
Biomedical Innovation Department, Scientific Research and High Education Center of Ensenada (CICESE), Carretera Ensenada-Tijuana No 3918 Fracc, Zona Playitas Ensenada C.P. 22860, Baja California, Mexico. oroz@cicese.edu.mx.
2
Cancer Center, Stanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. mnavarro@sbpdiscovery.org.
3
Biomedical Innovation Department, Scientific Research and High Education Center of Ensenada (CICESE), Carretera Ensenada-Tijuana No 3918 Fracc, Zona Playitas Ensenada C.P. 22860, Baja California, Mexico. karla.cervantes@icgeb.org.
4
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy. karla.cervantes@icgeb.org.
5
Biomedical Innovation Department, Scientific Research and High Education Center of Ensenada (CICESE), Carretera Ensenada-Tijuana No 3918 Fracc, Zona Playitas Ensenada C.P. 22860, Baja California, Mexico. alvarezc@cicese.mx.
6
Cancer Center, Stanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. gsalvesen@sbpdiscovery.org.
7
Biomedical Innovation Department, Scientific Research and High Education Center of Ensenada (CICESE), Carretera Ensenada-Tijuana No 3918 Fracc, Zona Playitas Ensenada C.P. 22860, Baja California, Mexico. lsanchez@cicese.edu.mx.
8
Biomedical Innovation Department, Scientific Research and High Education Center of Ensenada (CICESE), Carretera Ensenada-Tijuana No 3918 Fracc, Zona Playitas Ensenada C.P. 22860, Baja California, Mexico. alicea@cicese.mx.

Abstract

Lung cancer is one of the most common types of cancer in men and women and a leading cause of death worldwide resulting in more than one million deaths per year. The venom of marine snails Conus contains up to 200 pharmacologically active compounds that target several receptors in the cell membrane. Due to their diversity and specific binding properties, Conus toxins hold great potential as source of new drugs against cancer. We analyzed the cytotoxic effect of a 17-amino acid synthetic peptide (s-cal14.1a) that is based on a native toxin (cal14.1a) isolated from the sea snail Conus californicus. Cytotoxicity studies in four lung cancer cell lines were complemented with measurement of gene expression of apoptosis-related proteins Bcl-2, BAX and the pro-survival proteins NFκB-1 and COX-2, as well as quantification of caspase activity. Our results showed that H1299 and H1437 cell lines treated with s-call4.1a had decreased cell viability, activated caspases, and reduced expression of the pro-survival protein NFκB-1. To our knowledge, this is the first report describing activation of apoptosis in human lung cancer cell lines by s-cal14.1a and we offer insight into the possible mechanism of action.

KEYWORDS:

apoptosis; apoptotic-related genes; caspase-3 and -7; lung cancer; pathway; synthetic peptide

PMID:
26861394
PMCID:
PMC4773791
DOI:
10.3390/toxins8020038
[Indexed for MEDLINE]
Free PMC Article

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