Sesquiterpene Lactones as Promising Candidates for Cancer Therapy: Focus on Pancreatic Cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease which confers to patients a poor prognosis at short term. PDAC is the fourth leading cause of death among cancers in the Western world. The rate of new cases of pancreatic cancer (incidence) is 10 per 100,000 but present a 5-year survival of less than 10%, highlighting the poor prognosis of this pathology. Furthermore, 90% of advanced PDAC tumor present KRAS mutations impacting in several oncogenic signaling pathways, many of them associated with cell proliferation and tumor progression. Different combinations of chemotherapeutic agents have been tested over the years without an improvement of significance in its treatment. PDAC remains as one the more challenging biomedical topics thus far. The lack of a proper early diagnosis, the notable mortality statistics and the poor outcome with the available therapies urge the entire scientific community to find novel approaches against PDAC with real improvements in patients’ survival and life quality. Natural compounds have played an important role in the process of discovery and development of new drugs. Among them, terpenoids, such as sesquiterpene lactones, stand out due to their biological activities and pharmacological potential as antitumor agents. In this review, we will describe the sesquiterpene lactones with in vitro and in vivo activity against pancreatic tumor cells. We will also discuss the mechanism of action of the compounds as well as the signaling pathways associated with their activity.

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Therapeutics

“…Cancer certainly remains one of the most challenging health risks to humankind, and it is therefore no wonder that three out of the four reviews [15][16][17] focus entirely on NPs with anticancer activity and potential utility as leads against various neoplastic diseases. It is highly interesting and worth mentioning in this editorial that one particular class of NPs, sesquiterpene lactones (STLs), plays a major role in all three of these reviews.…”

“…Laurella et al [15] summarize the knowledge on STLs as inhibitors of pancreatic cancer, often associated with mutation of the K-ras oncogene, which these compounds appear to influence by interaction with the NF-κB, MAPK, and PI3K signaling pathways, all involved in tumor survival. Interestingly, most of the investigated STLs, some previously known to have anticancer potential, preferentially affected one or two of the mentioned signaling pathways, while the guaianolide aguerin B from a Centaurea (Asteraceae) species interfered with all three of them and thus appears to be a very promising candidate for deeper studies with the aim of developing new therapies for such prostate cancers.…”

“…Interestingly, most of the investigated STLs, some previously known to have anticancer potential, preferentially affected one or two of the mentioned signaling pathways, while the guaianolide aguerin B from a Centaurea (Asteraceae) species interfered with all three of them and thus appears to be a very promising candidate for deeper studies with the aim of developing new therapies for such prostate cancers. Among the compounds mentioned in the review [15] is the STL deoxyelephantopin from the Elephatopus species (Asteraceae), which had previously been demonstrated to act against cancer cells. The promising antitumor potential of this compound and its congener isodeoxyelephantopin is the subject of the review by Mehmood and Muanprasad [16].…”

Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata

“…An important structural feature of the SLs is the presence of a γ -lactone ring containing in many cases an α -methylene group. The biological activity (e.g., cytotoxic [ 1 , 5 , 6 , 7 , 8 ], anti-inflammatory [ 2 , 9 , 10 , 11 ]) of SLs is mainly due to the presence of this structural element [ 12 , 13 , 14 ]. Furthermore, there are also reports on neuroprotective [ 15 , 16 ], antimicrobial [ 17 ] or antiparasitic [ 18 , 19 ] activities of SL derivatives.…”

Editorial: Natural compounds as scaffolds for the discovery of new anti-cancer drugs: Focus on terpenoids and flavonoids

“…Natural compounds such as terpenoids and flavonoids have attracted the interest of many researchers. Sesquiterpene lactones and diterpenoids have shown to be promising groups for the development of potential antitumor agents due to their preferential selectivity over certain tumors and cell lines additionally acting on specific signaling pathways ( Laurella et al, 2022 ; Deng et al, 2022 ; Guo et al, 2022 ). Flavonoids have demonstrated a preventive effect in the development and progress of cancer and metastasis ( Guo et al, 2022 ; Ferreira et al, 2022 ).…”