In vitro studies have shown that Marina Crystal Minerals (MCM), a crystallized mixture of minerals and trace elements from sea water, possesses apoptotic and immune modulatory effects in human breast cancer cells MDA-MB-231. The current study aimed to evaluate MCM's anticancer effect in vivo against murine mammary adenocarcinoma cells and to explore its underlying mechanisms. Mice were inoculated intramuscularly with Ehrlich ascites carcinoma (EAC) cells, a breast adenocarcinoma. Tumors became palpable within 9 days. Tumor-bearing mice were injected with MCM intraperitoneally (IP) or intratumorally (IT) at a dose of 40 mg/kg BW for 6 days/week until day 28 post-inoculation. Tumor growth, cell cycle progression, cell cycle regulatory proteins, apoptosis, apoptotic regulatory markers, mitochondrial membrane potential (MMP), natural killer (NK) cell activity, and histopathological effects were investigated. Treatment with MCM reduced tumor volume by 49.4% for IP and 59.5% for IT injection. MCM induced cancer cell apoptosis, as indicated by a sub-G1 peak and confirmed by Annexin V/PI assay and histopathological examination. This was mediated by increased Bax expression, caspase-3 activation, decreased Bcl-2 expression, and MMP disruption. Furthermore, MCM treatment induced G1 cell cycle arrest, mediated through significantly increased expression of p53, p21, and p27 and decreased expression of cyclin D1 and PCNA in cancer cells. Finally, MCM treatment markedly enhanced NK cell cytotoxicity. MCM possesses chemopreventive potential to reduce tumor growth by suppressing cell proliferation, inducing apoptosis in EAC cells via a mitochondrial dependent pathway, and activating the immune system. Our results suggest MCM's beneficial potential for treating breast adenocarcinoma.
Keywords: Apoptosis; Breast cancer; Cell cycle; Ehrlich ascites carcinoma; Natural killer cell.
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