Antitumorigenic effect of insect-derived peptide poecilocorisin-1 in human skin cancer cells through regulation of Sp1 transcription factor

Malignant melanoma is highly resistant to conventional treatments and is one of the most aggressive types of skin cancers. Conventional cancer treatments are limited due to drug resistance, tumor selectivity, and solubility. Therefore, new treatments with fewer side effects and excellent effects should be developed. In previous studies, we have analyzed antimicrobial peptides (AMPs), which showed antibacterial and anti-inflammatory effects in insects, and some AMPs also exhibited anticancer efficacy. Anticancer peptides (ACPs) are known to have fewer side effects and high anticancer efficacy. In this study, the insect-derived peptide poecilocorisin-1 (PCC-1) did not induce toxicity in the human epithelial cell line HaCaT, but its potential as an anticancer agent was confirmed through specific effects of antiproliferation, apoptosis, and cell cycle arrest in two melanoma cell lines, SK-MEL-28 and G361. Additionally, we discovered a novel anticancer mechanism of insect-derived peptides in melanoma through the regulation of transcription factor Sp1 protein, which is overexpressed in cancer, apoptosis, and cell cycle-related proteins. Taken together, this study aims to clarify the anticancer efficacy and safety of insect-derived peptides and to present their potential as future therapeutic agents.

Curcumin Suppresses Tumorigenesis via Promoting SLC1A5-mediated Ferroptosis in Breast Cancer

Background: Breast cancer is one of the most malignant tumors in the female. Previous studies confirmed that Curcumin, a kind of polyphenol compound extract from the Curcuma longa underground rhizome, inhibits the survival of cancer cells. However, the functional role and mechanism of curcumin in breast cancer remain unclear.Methods: The cell counting kit-8 (CCK-8) assay was performed to examine the effect of curcumin on cell viability in both MDA-MB-453 and MCF-7 cells. Determination of lipid reactive oxygen species (ROS) level, malondialdehyde (MDA) production, and intracellular Fe2+ level was used to evaluate the effect of curcumin on cell ferroptosis. The protein levels were determined by western blot. A xenograft tumor model was employed to verify the antitumorigenic effect of curcumin on breast cancer in vivo.Results: Curcumin treatment significantly suppressed breast cancer cell viability in a dose-dependent manner. Moreover, curcumin triggered ferroptosis by enhancing the levels of lipid ROS, lipid peroxidation end-product MDA accumulation, and intracellular Fe2+. Mechanistically, curcumin administration impeded tumor growth via upregulating solute carrier family 1 member 5 (SLC1A5)-mediated ferroptosis in breast cancer. In vivo experiments showed that curcumin could effectively hamper the growth of tumors without noticeable side effects.Conclusion: We demonstrated that curcumin exhibits anti-tumorigenesis activity in breast cancer by promoting SLC1A5-mediated ferroptosis, providing a potential therapeutic agent for the treatment of breast cancer.

Elucidating the Role of the Maternal Embryonic Leucine Zipper Kinase in Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is an aggressive cancer with a 5-year survival rate <35%. Mortality remains high due to lack of targeted therapies. Using bioinformatic analyses, we identified maternal embryonic leucine zipper kinase (MELK) as 4.1-fold overexpressed in ACC compared with normal adrenal samples. High MELK expression in human tumors correlated with shorter survival and with increased expression of genes involved in cell division and growth. We investigated the functional effects of MELK inhibition using newly developed ACC cell lines with variable MELK expression, CU-ACC1 and CU-ACC2, compared with H295R cells. In vitro treatment with the MELK inhibitor, OTSSP167, resulted in a dose-dependent decrease in rates of cell proliferation, colony formation, and cell survival, with relative sensitivity of each ACC cell line based upon the level of MELK overexpression. To confirm a MELK-specific antitumorigenic effect, MELK was inhibited in H295R cells via multiple short hairpin RNAs. MELK silencing resulted in 1.9-fold decrease in proliferation, and 3- to 10-fold decrease in colony formation in soft agar and clonogenicity assays, respectively. In addition, although MELK silencing had no effect on survival in normoxia, exposure to a hypoxia resulted in a sixfold and eightfold increase in apoptosis as assessed by caspase-3 activation and TUNEL, respectively. Together these data suggest that MELK is a modulator of tumor cell growth and survival in a hypoxic microenvironment in adrenal cancer cells and support future investigation of its role as a therapeutic kinase target in patients with ACC.