Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches

Abstract

Cancer is a major cause of death and an impediment to increasing life expectancy worldwide. With the aim of finding new molecules for chemotherapeutic treatment of epidemiological relevance, ten alkaloid fractions from Amaryllidaceae species were tested against six cancer cell lines (AGS, BT-549, HEC-1B, MCF-7, MDA-MB 231, and PC3) with HaCat as a control cell line. Some species determined as critically endangered with minimal availability were propagated using in vitro plant tissue culture techniques. Molecular docking studies were carried out to illustrate binding orientations of the 30 Amaryllidaceae alkaloids identified in the active site of some molecular targets involved with anti-cancer activity for potential anti-cancer drugs. In gastric cancer cell line AGS, the best results (lower cell viability percentages) were obtained for Crinum jagus (48.06 ± 3.35%) and Eucharis bonplandii (45.79 ± 3.05%) at 30 µg/mL. The research focused on evaluating the identified alkaloids on the Bcl-2 protein family (Mcl-1 and Bcl-xL) and HK2, where the in vitro, in silico and statistical results suggest that powelline and buphanidrine alkaloids could present cytotoxic activity. Finally, combining experimental and theoretical assays allowed us to identify and characterize potentially useful alkaloids for cancer treatment.

Antitumor evaluation of amaryllidaceae alkaloids on cancer cell lines: A literature review

“…Moreover, amaryllidaceae alkaloids were found to trigger the release of cytochrome c from mitochondria, leading to caspase activation and apoptosis. These findings support the potential of amaryllidaceae alkaloids as effective agents for inducing cancer cell death [4,9,[10][11][12][13].…”

“…The studies reviewed demonstrated that these alkaloids possess significant growthinhibitory effects and induce apoptosis in various cancer cell types. The activation of apoptotic pathways and the downregulation of anti-apoptotic proteins indicate their potential as effective agents for inducing cancer cell death [4,11,18,20,34]. Furthermore, the anti-inflammatory properties of amaryllidaceae alkaloids suggest their potential role in attenuating tumor-associated inflammation.…”

“…Previous studies have reported that these alkaloids may exert selective cytotoxic effects on different cancer cell lines, inhibiting proliferation and inducing apoptosis in tumor cells [3]. This profile of activity positions them as potential candidates for the development of new anticancer therapies [4].…”

Lead Anticancer Agents of Crinine Alkaloids: Cytotoxic, Caspase-3, and Anti-angiogenic Exploration

“…The nine (9) crinine alkaloids selected for cytotoxicity studies (based on the criteria above) showed potential for activity against several cancer cell lines (at Pa > 0.5). Literature reports have shown that several crinine alkaloids demonstrate antiproliferative properties in several cancer cell lines [27]. In the current study, the alkaloids demonstrated the best activity against lung carcinoma (A549) and Oligodendroglioma (Hs683) cancer cell lines.…”