Abstract
Lung cancer is one of the most common types of cancer, accounting for approximately 15% of all cancer cases worldwide. Apoptosis is the dominant defense mechanism against tumor development. The balance between pro- and antiapoptotic members of the Bcl-2 protein family can determine cellular fate. The venom of predatory marine snails Conus is estimated to have 100–400 toxins called conotoxins. The family of α-conotoxins is known to consist of selective antagonists of nicotinic acetylcholine receptors (nAChRs). Lung cancer cells overexpress several subunits of nAChRs and are considered as an excellent target for new anticancer drugs. We compared the cytotoxic effect of two synthetic peptides derived from Californiconus californicus, Cal14.1a, and Cal14.1b, which only differ by one amino acid in their sequence, and compared their proapoptotic balance by Bax and Bcl-2 mRNA expression. We determined the caspase-3 and -7 activation to demonstrate apoptosis induction. Results showed that Cal14.1a induces a high Bax/Bcl-2 ratio in H1299 (lung cancer cells). Although Cal14.1b has a cytotoxic effect on H1299 cells, reducing cell viability by 30%, it does not increase the Bax/Bcl-2 ratio, which could be explained by the Glu in the 15th residue, which is crucial for the ability of Cal14.1a to induce apoptosis.
Highlights
Cancer is a significant public health problem worldwide
We evaluate the properties to induce apoptosis of synthetic peptide Cal14.1b; a synthetic peptide derived from Californiconus caifornicus that only differs in one amino acid from Cal14.1a, a Gly residue in position 15 instead of glutamic acid (Glu)
The cysteine pattern in Cal14.1a and Cal14.1b, and two prolines by first cysteine, are highly conserved with other conotoxins that are active against acetylcholine followed by first cysteine, are highly conserved with other conotoxins that are active against nicotinic receptors, such as It14a form Conus literattus, Pu14a from Conus pulicarius, and ts14a acetylcholine nicotinic receptors, such as It14a form Conus literattus, Pu14a from Conus from Conus tessulatus [40,41,42]
Summary
Cancer is a significant public health problem worldwide. Lung cancer is one of the leading causes of cancer-related mortality throughout the world. Even though chemotherapy is the most effective treatment for most malignant tumors [3], a variety of chemotherapeutics can cause severe side effects, such as vomiting, nausea, diarrhea, constipation, oral and gastrointestinal mucositis that lead to anorexia, malabsorption, weight loss, anemia, fatigue, and sepsis [6], leading to painful symptoms that result in the interruption of cancer treatment [3]. It is common for neoplastic cells to carry mutations in cell-death-related genes that allow them to survive despite treatment and increase their ability to invade different tissues and organs [7,8]. Apoptosis is the dominant defense mechanism against tumor development, and it is essential for immunity, growth, and tissue homeostasis [9,10].
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