Journal of ethnopharmacology · 2025
Antitumor activity and mechanism of action of alkaloids from Alocasia macrorrhiza (giant taro) against nasopharyngeal carcinoma in vitro and in vivo: First identification of AMD-8's ATM inhibitory role in nasopharyngeal carcinoma.
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Wang Lutong, Xu Jingwen, Shen Liyuan, Gao Jianxin, Li Lin, Wang Yihai, He Xiangjiu
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Alocasia macrorrhiza (Giant taro), widely cultivated in tropical areas, especially southern China, has long been used in folk medicine for treating cancers, including nasopharyngeal carcinoma (NPC).
AIM OF THE STUDY: This study evaluated the anti-nasopharyngeal carcinoma effects of the total alkaloids of A. macrorrhiza (AMA) and AMD-8, a bioactive alkaloid isolated from AMA, and investigated the underlying mechanisms.
MATERIALS AND METHODS: In vitro, MTT and colony formation assays assessed antiproliferative activity, while apoptosis and DNA damage were analyzed by Hoechst staining, Annexin V/PI flow cytometry, immunofluorescence, and Western blot. In vivo, the efficacy and safety were examined using a CNE1 xenograft model in BALB/c-nude mice. Transcriptomic analysis of tumor tissue was performed to explore pharmacological mechanisms.
RESULTS: AMA and AMD-8 showed strong cytotoxicity against CNE1 (IC50 = 30.80 μg/mL and 22.53 μM) and CNE2 cells (IC50 = 30.54 μg/mL and 27.93 μM). Both induced apoptosis (up to 40 %) and DNA damage, with cell cycle arrest at G2/M phase (CNE1) and G0/G1 phase (CNE2). AMA also disrupted the homologous recombination repair (HRR) pathway. In vivo, AMA significantly inhibited tumor growth with well-tolerability. Transcriptomics analysis showed changes in cell cycle and HRR. Western blot confirmed AMA promoted apoptosis and suppressed HRR in tumors. The up-regulated expression of cleaved-caspase-3 and PARP1 suggested that AMA promoted apoptosis, the decreased BRCA2, ATM, CtIP, NBS1, Rad54 and Rad51 confirmed AMA suppressed HRR.
CONCLUSION: AMA demonstrates significant antitumor activity against NPC by inducing apoptosis, causing cell cycle arrest, and inhibiting HRR. These findings suggest AMA as a promising therapeutic or adjuvant agent for NPC.
AIM OF THE STUDY: This study evaluated the anti-nasopharyngeal carcinoma effects of the total alkaloids of A. macrorrhiza (AMA) and AMD-8, a bioactive alkaloid isolated from AMA, and investigated the underlying mechanisms.
MATERIALS AND METHODS: In vitro, MTT and colony formation assays assessed antiproliferative activity, while apoptosis and DNA damage were analyzed by Hoechst staining, Annexin V/PI flow cytometry, immunofluorescence, and Western blot. In vivo, the efficacy and safety were examined using a CNE1 xenograft model in BALB/c-nude mice. Transcriptomic analysis of tumor tissue was performed to explore pharmacological mechanisms.
RESULTS: AMA and AMD-8 showed strong cytotoxicity against CNE1 (IC50 = 30.80 μg/mL and 22.53 μM) and CNE2 cells (IC50 = 30.54 μg/mL and 27.93 μM). Both induced apoptosis (up to 40 %) and DNA damage, with cell cycle arrest at G2/M phase (CNE1) and G0/G1 phase (CNE2). AMA also disrupted the homologous recombination repair (HRR) pathway. In vivo, AMA significantly inhibited tumor growth with well-tolerability. Transcriptomics analysis showed changes in cell cycle and HRR. Western blot confirmed AMA promoted apoptosis and suppressed HRR in tumors. The up-regulated expression of cleaved-caspase-3 and PARP1 suggested that AMA promoted apoptosis, the decreased BRCA2, ATM, CtIP, NBS1, Rad54 and Rad51 confirmed AMA suppressed HRR.
CONCLUSION: AMA demonstrates significant antitumor activity against NPC by inducing apoptosis, causing cell cycle arrest, and inhibiting HRR. These findings suggest AMA as a promising therapeutic or adjuvant agent for NPC.