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Toxicity and Anti-Proliferative Properties of Anisomeles indica Ethanol Extract on Cervical Cancer HeLa Cells and Zebrafish Embryos.

ABSTRACT: In this study, we showed that crude extract of Anisomeles indica (AI-EtE) expressed its toxicity to HeLa cells with an IC50 dose of 38.8 µg/mL and to zebrafish embryos with malformations, lethality and hatching inhibition at 72-hpf at doses higher than 75 µg/mL. More interestingly, flow cytometry revealed that AI-EtE significantly promoted the number of cells entering apoptotic. Accordingly, the transcript levels of BAX, CASPASE-8, and CASPASE-3 in the cells treated with AI-EtE at IC50 dose were 1.55-, 1.62-, and 2.45-fold higher than those in the control cells, respectively. Moreover, treatment with AI-EtE caused cell cycle arrest at the G1 phase in a p53-independent manner. Particularly, percentages of AI-EtE-treated cells in G1, S, G2/M were, respectively 85%, 6.7% and 6.4%; while percentages of control cells in G1, S, G2/M were 64%, 15% and 19%, respectively. Consistent with cell cycle arrest, the expressions of CDKN1A and CDNK2A in AI-EtE-treated cells were up-regulated 1.9- and 1.64-fold, respectively. Significantly, treatment with AI-EtE also decreased anchorage-independent growth of HeLa cells. In conclusion, we suggest that Anisomeles indica can be considered as a medicinal plant with a possible use against cervical cancer cells; however, the used dose should be carefully monitored, especially when applying to pregnant women.

SUBMITTER: Bich-Loan NT

PROVIDER: S-EPMC8003830 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Toxicity and Anti-Proliferative Properties of Anisomeles indica Ethanol Extract on Cervical Cancer HeLa Cells and Zebrafish Embryos.

Bich-Loan Nguyen T NT Kien Kieu Trung KT Thanh Nguyen Lai NL Kim-Thanh Nguyen T NT Huy Nguyen Quang NQ The-Hai Pham P Muller Marc M Nachtergael Amandine A Duez Pierre P Thang Nguyen Dinh ND

Life (Basel, Switzerland) 20210320 3

In this study, we showed that crude extract of Anisomeles indica (AI-EtE) expressed its toxicity to HeLa cells with an IC50 dose of 38.8 µg/mL and to zebrafish embryos with malformations, lethality and hatching inhibition at 72-hpf at doses higher than 75 µg/mL. More interestingly, flow cytometry revealed that AI-EtE significantly promoted the number of cells entering apoptotic. Accordingly, the transcript levels of BAX, CASPASE-8, and CASPASE-3 in the cells treated w ...[more]

PMID: 33804714

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Project description:BackgroundZuojin formula, a traditional Chinese medicine, comprises Coptis chinensis and Evodia rutaecarpa. In our previous study, the total alkaloid extract from Zuojin formula (TAZF) showed potent and improved efficacy. However, its safety and toxicokinetics remain unknown. The objective of this study was to evaluate the safety of repeated administrations of TAZF and investigate the internal exposure of the main components and its relationship with toxic symptoms.MethodsSprague-Dawley rats were orally administered TAZF at 0.4, 1.2 and 3.7 g/kg for 28 days, which was followed by a 14-day recovery period. The toxic effects were evaluated weekly by assessing body weight changes, food intake, blood biochemistry and haematological indices, organ weights and histological changes. A total of eight components were detected, including berberine, coptisine, epiberberine, palmatine, jatrorrhizine, columbamine, evodiamine, and rutaecarpine. The toxicokinetic profiles of the eight components were investigated after single and repeated administrations. Linear mixed effect models were applied to analyse the associations between internal exposure and toxic symptoms. Network pharmacology analysis was applied to explore the potential toxic mechanisms.ResultsCompared with the vehicle group, the rats in the low- and medium-dose groups did not show noticeable abnormal changes, while rats in the high-dose group exhibited inhibition of weight gain, a slight reduction in food consumption, abdominal bloating and atrophy of the splenic white pulp during drug administration. The concentration of berberine in plasma was the highest among all compounds. Epiberberine was found to be associated with the inhibition of weight gain. Network pharmacology analysis suggested that the alkaloids might cause abdominal bloating by affecting the proliferation of smooth muscle cells. The benchmark dose lower confidence limits (based on body weight inhibition) of TAZF were 1.27 g/kg (male) and 1.91 g/kg (female).ConclusionsTAZF has no notable liver or kidney toxicity but carries risks of gastrointestinal and immune toxicity at high doses. Alkaloids from Coptis chinensis are the main plasma components related to the toxic effects of TAZF.

Dataset Information

Toxicity and Anti-Proliferative Properties of Anisomeles indica Ethanol Extract on Cervical Cancer HeLa Cells and Zebrafish Embryos.

Publications

Toxicity and Anti-Proliferative Properties of <i>Anisomeles indica</i> Ethanol Extract on Cervical Cancer HeLa Cells and Zebrafish Embryos.

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