RESUMEN
Vernonia glaberrima leaves are traditionally used to alleviate bodily pain, skin cancer, and other skin-related disorders. The purpose of the study was to investigate the acute and sub-acute toxicity of 5-methylcoumarin-4ß-glucoside, a promising chemotherapeutic agent against colon cancer isolated from the leaves of Vernonia glaberrima. 5-methylcoumarin-4ß-glucoside was isolated from the methanol leaf extract of Vernonia glaberrima following a previously described method. The acute toxicity study involved a two-phase 24 h observation for signs of mortality and toxicity following single oral dose administration of the isolated compound. For the sub-acute study, four groups of mice, averagely aged eight weeks, were administered graded doses of the compound (250, 500 and 1000 mg/kg) or vehicle for 28 days. On the 29th day, the mice were fasted, anesthetized, euthanized, then their blood and tissues were harvested for hematological, biochemical and histopathological evaluations. There were no signs of mortality or moribund status with an increasing dose of up to 5000 mg/kg over a 24 h period in the acute study. Also, there was no evidence of toxicity on the biochemical or hematopoietic systems in the sub-acute study (p < 0.05). At the dose of 1000 mg/kg, the mice showed some distorted histology with no corresponding alterations in serum biochemicals. Overall, the results showed that 5-methylcoumarin-4ß-glucoside at dosages up to 500 mg/kg is tolerable in mice.
RESUMEN
Cancer metastasis research has emerged in recent years as one of the most important topics of debate in the discovery and development of novel anticancer therapies. Colorectal cancer (CRC), the third most common cancer worldwide, has a high mortality rate due to recurrence and distant metastasis to the liver. Several non-coding RNAs (ncRNAs) have been linked to metastatic CRC (mCRC), including the long non-coding RNA (lncRNA) Metastasis-Associated Lung-Adenocarcinoma Transcript 1 (MALAT1). MALAT1 is an RNA that has been linked to tumor cell proliferation, progression, epithelial-mesenchymal transition (EMT), cell migration and invasion, metastasis, and survival in mammalian species. Previously, there was no convincing evidence linking MALAT1 to mCRC. Studies have shown that MALAT1 functions as a competitive endogenous RNA (ceRNA) with microRNAs (miRNAs) and interacts directly with oncogenes and proteins. This RNA also activates several signaling pathways, including Wnt/ß-catenin, PI3K/Akt/mTOR, and EMT. Meanwhile, standard chemotherapy and immunotherapy are the current treatment options for mCRC patients. However, evidence-based studies have recently demonstrated that inhibiting the MALAT1 RNA transcript can be considered as a treatment option for mCRC, highlighting the need to investigate its roles as a therapeutic target in mCRC. Thus, in this review, we looked at studies that linked MALAT1 to multiple signaling pathways implicated in mCRC, as well as its potential as a therapeutic target for the treatment of mCRC.