Florencio, K. G. D. | Search bioRxiv

bioRxiv2025

Anticancer potential of piericidin A1 and derivatives isolated from Streptomyces sp. associated with Palythoa variabilis from Brazilian Reefs

Marine holobionts are prolific sources of bioactive natural products. Previously, our group investigated cytotoxic compounds in zoantharians of the genus Palythoa and, herein, we further explored the anticancer potential of marine bacteria associated with P. variabilis. After isolating 10 culturable bacterial strains, we screened for cytotoxic activity on metastatic prostate tumor cells (PC-3/M) using the MTT assay. The crude extract of one of the strains (BRA-035), identified as Streptomyces sp., was selected due to its bioactivity profile and submitted to cytotoxicity-guided fractionation. This approach allowed us to isolate piericidin A1 and identify other 2 piericidin derivatives. Piericidin A1 displayed a wide range of potency, with IC50 varying from pM to low nM for several tumor cells (OVCAR, PC-3, PC-3/M, HCT-116) or non active (IC50 >12uM) for leukemia cell line (HL-60) and murine melanoma (B16-F10). Overall, our findings demonstrate that P. variabilis hosts bacteria with biotechnological potential, confirming piericidin A1 as a promising candidate for anticancer applications.

pharmacology and toxicology↗

bioRxiv2021

Chromomycin A5 induces bonafide immunogenic cell death in metastatic melanoma

Some first-line cytotoxic chemotherapics, e.g. doxorubicin, paclitaxel and oxaliplatin, induce activation of the immune system through immunogenic cell death (ICD). Tumor cells undergoing ICD function as a vaccine, releasing damage-associated molecular patterns (DAMPs), which act as adjuvants, and neoantigens of the tumor are recognized as antigens. ICD induction is rare, however it yields better and long-lasting antitumor responses to chemotherapy. Advanced metastatic melanoma (AMM) is incurable for more than half of patients. The discovery of ICD inducers against AMM is an interesting drug discovery strategy with high translational potential. Here we evaluated ICD induction of four highly cytotoxic chromomycins A (CA5-8). B16-F10, a metastatic melanoma cell line, treated with CA5-8 and doxorubicin exhibited ICD features such as autophagy and apoptosis, externalization of calreticulin, and releasing of HMGB1. However, CA5-treated cells had the best profile, also inducing ATP release, ERp57 externalization, phosphorylation of eIF2 and altering expression of transcription of genes related to autophagy, endoplasmic reticulum stress, and apoptosis. Bonafide ICD induction by CA5 was confirmed by a C57BL/6 mice vaccination assay with CA5-treated cells. These findings support a high potential of CA5 as an anticancer candidate against AMM.

immunology↗