Insights on Antitumor Activity and Mechanism of Natural Benzophenanthridine Alkaloids

Abstract

Benzophenanthridine alkaloids are a class of isoquinoline compounds, which are widely found in the plants of papaveraceae, corydalis, and rutaceae. Biological activities and clinical studies have shown that benzophenanthridine alkaloids have inhibitory effects on many cancers. Considering that the anticancer activities and mechanisms of many natural benzophenanthridine alkaloids have been discovered in succession, the purpose of this paper is to review the anticancer effects of benzophenanthridine alkaloids and explore the application potential of these natural products in the development of antitumor drugs. A literature survey was carried out using Scopus, Pubmed, Reaxys, and Google Scholar databases. This review summarizes and analyzes the current status of research on the antitumor activity and antitumor mechanism of natural products of benzophenanthridine from different sources. The research progress of the antitumor activity of natural products of benzophenanthridine from 1983 to 2023 was reviewed. The antitumor activities of 90 natural products of benzophenanthridine and their related analogues were summarized, and the results directly or indirectly showed that natural products of benzophenanthridine had the effects of antidrug-resistant tumor cell lines, antitumor stem cells, and inducing ferroptosis. In conclusion, benzophenanthridine alkaloids have inhibitory effects on a variety of cancers and have the potential to counteract tumor resistance, and they have great application potential in the development of antitumor drugs.

Ferroptosis-Regulated Natural Products and miRNAs and Their Potential Targeting to Ferroptosis and Exosome Biogenesis

“…Quercetin [101] Breast Ca ↑ ATF3 [102], HMOX1 [103] ↓ SLC40A1 [104], FTL [105], SP1 [106] Ruscogenin [31] Pancreas Ca ↑ TF [31,107] ↓ SLC40A1 [107] Salinomycin [108] Head/neck Ca ↑ ATF3 [109], ATF4 [110], ATG5, ATG7 [111], DPP4 [112], IREB2, TFRC [108,113] ↓ FTH1, FTL [113], NFE2L2, GCLC [114], HIF1A [115], TP53 [116], FTH1 [108] Sanguinarine [117,118] Cervical Ca ↓ SLC7A11 [118] Solasonine [31] Liver Ca ↓ GPX4, GSS [119], SLC7A11 [120] Sulforaphane [121] Leukemia…”

“…A study mentioned that nitidine chloride inhibited the proliferation of lung cancer cells by downregulating the ferroptosis-inhibiting NEDD4 gene [ 93 ]. Moreover, other natural benzophenanthridine alkaloids, such as sanguinarine [ 117 ], also induce ferroptosis in cervical cancer cells by downregulating SLC7A11 [ 118 ].…”

Exploiting cell death and tumor immunity in cancer therapy: challenges and future directions

“…A photoactivated oxygen self-supplying chemical photothermal nanoplatform enhances ferroptosis and alleviates hypoxia-induced chemoresistance in colorectal cancer (CRC) ( Jiang et al, 2023 ). Phenanthroindolizidine alkaloids, natural products that inhibit various cancers, show promise in overcoming tumor resistance ( Peng et al, 2023 ). Combining carbon ion radiotherapy (CIRT) with immunotherapy enhances immune cell infiltration, suggesting a potential role for ferroptosis in synergistic anticancer effects during CIRT combined therapy ( Huang Q. et al, 2023 ).…”

N-Methoxycarbonyl-9,12-Dimethoxy-Norchelerythrine: A Novel Antifungal Type-III Benzo[c]phenanthridine from Zanthoxylum simulans Hance Seedlings

“…The distribution of benzophenanthridine alkaloids across various plant species highlights the importance of exploring different botanical sources for novel compounds with diverse potential applications [6]. The bioactivity of benzophenanthridine alkaloids has acquired significant interest due to their potential as therapeutic agents [8]. Sanguinarine (2), for instance, exhibits potent antimicrobial activity against a range of pathogens, including bacteria, fungi, protozoa, and other relevant biological properties [9].…”