Aristolochia olivieri Colleg. ex Boiss.: A Promising Natural Resource for Gastric Cancer Prevention

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Gastric cancer, a complex and multifaceted disease, encompasses various subtypes, such as adenocarcinoma, ring cell carcinoma, and undifferentiated carcinoma, according to WHO guidelines [1].

This global health concern is a leading cause of mortality, with disparate incidence rates across regions, being particularly prevalent in East Asia, Eastern Europe, Central, and South America, while relatively rare in Italy [2,3].

Epidemiology and Risk Factors: Approximately 90% of gastric cancer cases are sporadic, primarily affecting individuals aged 45 and above, with a higher incidence in males. Cases below the age of 45 are infrequent, constituting about 10% of the total [4]. Several environmental factors contribute to gastric cancer risk, including H. pylori infection, dietary habits, tobacco smoking, and inflammation [5,6].

Treatment Modalities: The mainstay treatments for gastric cancer include chemotherapy and surgery, underscoring the importance of early detection and intervention [7]. However, in the quest for more effective preventive measures, the exploration of food and plant-derived substances inducing apoptosis has gained attention.

Phytocomplexes and Isolated Compounds: Preclinical studies have shown promising results with various food substances [8]. Extracts from hibiscus, for example, displayed cytotoxic effects on gastric adenocarcinoma cells without adverse effects on cardiovascular and central nervous systems [9-11].

Compounds like sarracenin and caffeic acid methyl ester isolated from Patrinia heterophylla Bunge roots exhibited selective inhibition of carcinoma cells [12]. Polyphenols, including flavonoids, phenolic acids, stilbens, and diarylheptanoids, have demonstrated inhibitory effects towards gastric cancer cells [13], aligning with epidemiological studies suggesting a decreased risk with a polyphenol-rich diet, particularly in females [14].

Innovative Approaches: Motivated by the potential of natural compounds, our study focused on Aristolochia olivieri Colleg. ex Boiss., a plant with historical use in Kurdish folk medicine for gastrointestinal ailments. Choosing a methanolic extract facilitated a comprehensive examination of the plant’s chemical composition, with a focus on phenolic acids and flavonoids known for their anticancer potential.

Methodology: Our study involved a thorough evaluation of the chemical composition and in vitro antibacterial and anticancer effects of a methanolic extract from the aerial parts of Aristolochia olivieri Colleg. ex Boiss. We aimed to understand the plant’s potential in addressing gastric cancer.

Results: The analysis revealed the presence of several phenolic acids and flavonoids in the methanolic extract. In vitro experiments demonstrated significant anticancer activities through apoptosis, validating the potential of Aristolochia olivieri Colleg. ex Boiss. as a promising resource for innovative approaches in gastric cancer management.

Discussion

Gastric cancer is a multifactorial disease influenced by genetic, environmental, and lifestyle factors, making it a global health concern. In this study, we explored the potential of Allium obliquum L. methanolic extract (AOME) as a preventive strategy against gastric cancer, particularly in individuals with Helicobacter pylori infection, a major risk factor for the disease.

The exposome, encompassing lifelong environmental exposures, plays a crucial role in gastric cancer development. Our focus on investigating the anti-H. pylori and anticancer properties of AOME aligns with the current interest in developing preventive strategies for gastric cancer. Despite the challenges posed by the high concentration required for antibacterial activity, our study shifted towards exploring the in vitro effects of AOME against gastric cancer cells.

AOME’s chemical composition, notably rich in compounds like p-hydroxybenzoic acid, 3-hydroxybenzoic acid, caffeic acid, and p-coumaric acid, sets it apart from other plants within the same genus. The significant concentrations of these compounds prompted us to investigate the antibacterial and anticancer activities of AOME.

Our findings revealed a substantial antibacterial activity against H. pylori, albeit at a relatively high concentration. To circumvent the challenges associated with direct antibacterial applications, we redirected our focus to the in vitro effects of AOME on gastric cancer cells. The observed alterations in cellular morphology, such as vacuolization, changes in mitochondrial structure, and signs of autophagy and mitophagy, suggest AOME’s potential in inducing apoptosis.

While our study primarily focused on morphological changes, the observed effects offer valuable preliminary insights into AOME’s potential role in apoptosis induction in gastric cancer cells. The lack of detailed molecular pathway exploration leaves room for future research to delve deeper into the underlying mechanisms.

Comparing the IC50 values of individual compounds reported in the literature, caffeic acid, rutin, and quercetin emerged as potential contributors to AOME’s observed effects. These polyphenols, acting through a multitarget mechanism, induce apoptotic bleb formation and affect key molecular pathways related to apoptosis.

The ultrastructural changes observed, such as bleb formation, chromatin margination, and apoptotic bodies, support the apoptotic effects of AOME polyphenols. The synergistic interaction among the diverse bioactive compounds in AOME may contribute to the observed cytotoxic and apoptotic effects, suggesting a complex interplay.

While some compounds were detected at low concentrations, ellagic acid, p-coumaric acid, gallic acid, and quercetin may complementarily contribute to AOME’s apoptotic effects. The multifaceted approach involving different pathways, such as apoptosis, migration, inflammation, and ROS-mediated pathways, highlights the potential of AOME in combating gastric cancer.

Synergy among the bioactive compounds in AOME could amplify their cytotoxic and apoptotic effects, providing a more potent anticancer effect than the sum of individual contributions. This suggests that the AOME extract, despite containing compounds at subactive concentrations, may act in concert to exert a more significant impact on gastric cancer cells.

Conclusion: In conclusion, our study underscores the importance of exploring natural compounds for gastric cancer prevention. Aristolochia olivieri Colleg. ex Boiss., with its rich chemical composition and demonstrated anticancer properties, emerges as a novel resource. Further research is warranted to elucidate its mechanisms of action and to explore its potential role in developing innovative chemopreventive strategies for gastric cancer. The findings contribute to the growing body of evidence supporting the integration of natural compounds into comprehensive cancer prevention strategies.


reference link : https://www.mdpi.com/1422-0067/24/21/16003

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