Nutrients, Vol. 18, Pages 1198: Cyanidin-3-O-Glucoside-Rich Black Rice Fraction Attenuates IL-1β/IL-6-Driven A549 Lung Cancer Cell Migration and Invasion and Modulates JAK1/STAT3 Signaling
Nutrients doi: 10.3390/nu18081198
Authors:
Warathit Semmarath
Punnida Arjsri
Kamonwan Srisawad
Intranee Intanil
Sansanee Jamjod
Chanakan Prom-u-thai
Pornngarm Dejkriengkraikul
Background/Objectives: Inflammatory mediators within the tumor microenvironment contribute to lung cancer progression by enhancing cellular motility and invasive capacity through cytokine-dependent signaling networks. Modulation of these inflammation-associated pathways by dietary bioactive compounds may provide complementary strategies for limiting cancer aggressiveness. Our objective was to examine the inhibitory effects of a cyanidin-3-O-glucoside (C3G)-rich fraction from Kum Akha pigmented black rice (CKAB-P1) on inflammation-stimulated A549 cancer cell progression. Methods: CKAB-P1 was obtained through solvent-partition extraction and chemically characterized using the pH differential method and high-performance liquid chromatography. A549 cells were pretreated with CKAB-P1 or C3G, followed by stimulation with conditioned medium predominantly containing IL-6 and IL-1β derived from LPS-exposed THP-1 macrophages (THP-1-CS). Effects on cancer cell migration and invasion were evaluated using wound-healing, Transwell invasion, gelatin zymography, and Western blot analyses. Results: CKAB-P1 contained 106.62 ± 3.54 mg/g extract of total anthocyanins, with C3G representing the major constituent (59.42 ± 2.54 mg/g extract). Exposure of THP-1-CS stimulated migration and invasion of A549 lung cancer, and neutralization of IL-6 and IL-1β reduced these pro-migratory effects, confirming cytokine involvement. Treatment with CKAB-P1 (10–40 μg/mL) or C3G (2.5–20 μg/mL) markedly attenuated inflammation-enhanced migration and invasion (p < 0.05). A reduction in MMP-2 and MMP-9 activity, along with decreased expression of invasion-associated protein expressions (uPA, uPAR, and MT1-MMP), was observed. Furthermore, both CKAB-P1 and C3G attenuated phosphorylation of JAK1 and STAT3. Conclusions: These findings suggest that anthocyanin-enriched black rice fraction may limit inflammation-driven A549 lung cancer cell aggressiveness through modulation of the cytokine-driven JAK1/STAT3 signaling cascade, indicating its potential relevance as a bioactive dietary component targeting tumor-associated inflammatory signaling.
Background/Objectives: Inflammatory mediators within the tumor microenvironment contribute to lung cancer progression by enhancing cellular motility and invasive capacity through cytokine-dependent signaling networks. Modulation of these inflammation-associated pathways by dietary bioactive compounds may provide complementary strategies for limiting cancer aggressiveness. Our objective was to examine the inhibitory effects of a cyanidin-3-O-glucoside (C3G)-rich fraction from Kum Akha pigmented black rice (CKAB-P1) on inflammation-stimulated A549 cancer cell progression. Methods: CKAB-P1 was obtained through solvent-partition extraction and chemically characterized using the pH differential method and high-performance liquid chromatography. A549 cells were pretreated with CKAB-P1 or C3G, followed by stimulation with conditioned medium predominantly containing IL-6 and IL-1β derived from LPS-exposed THP-1 macrophages (THP-1-CS). Effects on cancer cell migration and invasion were evaluated using wound-healing, Transwell invasion, gelatin zymography, and Western blot analyses. Results: CKAB-P1 contained 106.62 ± 3.54 mg/g extract of total anthocyanins, with C3G representing the major constituent (59.42 ± 2.54 mg/g extract). Exposure of THP-1-CS stimulated migration and invasion of A549 lung cancer, and neutralization of IL-6 and IL-1β reduced these pro-migratory effects, confirming cytokine involvement. Treatment with CKAB-P1 (10–40 μg/mL) or C3G (2.5–20 μg/mL) markedly attenuated inflammation-enhanced migration and invasion (p < 0.05). A reduction in MMP-2 and MMP-9 activity, along with decreased expression of invasion-associated protein expressions (uPA, uPAR, and MT1-MMP), was observed. Furthermore, both CKAB-P1 and C3G attenuated phosphorylation of JAK1 and STAT3. Conclusions: These findings suggest that anthocyanin-enriched black rice fraction may limit inflammation-driven A549 lung cancer cell aggressiveness through modulation of the cytokine-driven JAK1/STAT3 signaling cascade, indicating its potential relevance as a bioactive dietary component targeting tumor-associated inflammatory signaling. Read More